Human Immunodeficiency Virus (HIV)
Human immunodeficiency virus (HIV) or AIDS (acquired
immunodeficiency syndrome) virus, is a virus that causes defects in the human
immune system. In 1981, the human immunodeficiency virus was first discovered
in Central America. It is a lentivirus that infects cells of the human immune
system, a type of retrovirus.
On October 27, 2017, the World Cancer Organization’s
International Agency for Research on Cancer published a preliminary list of
carcinogens. Human immunodeficiency virus type 1 (infection) is in the list of
first-class carcinogens. In the list of category 2B carcinogen.
Scientific name:
Human immunodeficiency virus
Latin name: Human Immunodeficiency
Virus (HIV)
Nickname: AIDS
Boundary: Virology
Branch: RNA Virus
Distribution Area:
Global
Table of Content
1 Source
2 Morphological
characteristics
▪ Morphological
structure
▪ Coding genes
▪ Virus
characteristics
3 Virus Development
▪ First Discovery
▪ Virus naming
▪ Virus status
▪ Antibody negative
4 Survival
conditions
▪ Survival in vitro
▪ Inactivation
method
▪ Humoral survival
5 Ways of infection
▪ Transmission
▪ Pathogenic
mechanism
6 Hideout
▪ Intestinal lymph
nodes
▪ Memory T cells
▪ CD4 cells
7 Testing methods
▪ Antibody testing
▪ Antigen detection
▪ Nucleic acid
detection
8 Training methods
9 Main symptoms
▪ Suspected
symptoms
▪ Asymptomatic
latent
10 Human damage
▪ Eroded cells
▪ Ignore antibodies
▪ Help cancer
▪ Take life
11 Vaccine Development
12 Research
Progress
▪ Origin doubt
▪ Hijacking cells
▪ Virus antibodies
▪ Activate latency
▪ Remove virus
13 Cure cases
What is the Source of HIV(Human immunodeficiency virus)?
On March 4, 2015, scientists from multiple countries found
that the four known strains of HIV are from chimpanzees and gorillas in
Cameroon. This is the first time that all sources of HIV strains have been
fully identified.
There are four known HIV strains, namely M, N, O and P, each
with a different source. Among them, the most widely spread M and N have long
been confirmed to be from chimpanzees, but the rarer O and P are It was later
confirmed that both O and P were gorillas from southwest Cameroon.
There are only two P-type cases in the world so far, and
O-type is only 100,000, mainly in Central and West Africa.
What are the Morphological Characteristics of HIV (Human immunodeficiency virus)?
Morphology of HIV: The human immunodeficiency virus is approximately 120
nanometers in diameter and is roughly spherical. The outer membrane of the
virus is a lipid envelope derived from the host cell and embedded with the
viral proteins gp120 and gp41.
gp41 is a transmembrane protein, gp120 is located on the
surface and binds to gp41 through non-covalent interactions. Inwards are a
spherical matrix formed by protein p17 and a semi-conical capsid formed by
protein p24.
The capsid shows a high electron density under an electron
microscope.
The capsid contains
the viral RNA genome, enzymes (reverse transcriptase, integrase, protease) and
other components from the host cell (such as tRNAlys3, used as primers for
reverse transcription).
What is the Coding Gene of HIV (Human immunodeficiency virus)?
The viral genome is two identical positive-strand RNAs, each
of which is approximately 9.2-9.8 kb in length.
The two ends are long terminal repeats (LTR), which contain
cis-regulatory sequences to control the expression of the provirus.
It has been shown that LTR has promoters and enhancers and
contains negative regulatory regions.
The sequence between LTRs encodes at least 9 proteins, which
can be divided into three categories: structural proteins, regulatory proteins
and accessory proteins.
1. The gag gene encodes a polymer precursor protein composed
of about 500 amino acids, which is hydrolyzed by protease to form nuclear
proteins P17 and P24, which protects RNA from damage by external nucleases.
2. The Pol gene encodes a polymerase precursor protein, which
is cut to form a protease, an integrase and a reverse transcriptase (both
having DdRp and ribonuclease H functions), all of which are necessary for virus
proliferation.
3. The env gene encodes a precursor protein of about 863
amino acids and is glycosylated into gp160, gp120 and gp41. gp120 contains
neutralizing antigenic determinants.
It has been proved that HIV neutralizes
epitopes.
On the gp120 V3 loop, the V3 loop is an important functional region
of the envelope protein and plays an important role in the fusion of virus and
cells. gp120 is linked to the transmembrane protein gp41 by a non-covalent
bond.
The fusion of gp41 with the target cell causes the virus to enter the
cell.
Experiments have shown that gp41 is also highly antigenic and can induce
antibody responses.
4. The protein encoded by TaT gene can be combined with LTR
to increase the transcription rate of all viral genes, and also can promote the
translation of viral mRNA after transcription.
5. Rev gene product is a cis-activating factor, which can
inhibit the cis-acting repression sequance (Crs) in env and gag, and enhance
the expression of gag and env genes to synthesize corresponding virus
structural proteins. .
6. Nef gene encoding protein P27 has a negative regulatory
effect on HIV gene expression to delay virus replication. This protein acts on
the LTR of HIv cDNA and inhibits integrated viral transcription. It may be
necessary for HIV to maintain a sense of persistence in the body.
7. The Vif gene is not essential for HIV, but may affect free
HIV infectivity, virion production, and in vivo transmission.
8. The VPU gene is unique to HIV-1, and is essential for
effective replication of HIV and assembly and maturation of virions.
9. The protein encoded by the Vpr gene is a weak
transcriptional activator and plays a role in the in vivo reproduction cycle.
HIV-2 gene structure is different from HIV-1: It does not
contain VPU gene, but has a VPX gene of unknown function.
Nucleic acid
hybridization examined the nucleotide sequences of HIV-1 and HIV-2, which were
only 40% identical. Env gene expression products stimulate the body to produce
antibodies without cross-reactivity.
What are the Human Immunodeficiency Virus Characteristics?
The auxiliary T lymphocyte system mainly attacks the human
body. Once it invades the body cells, the virus will integrate with the cells
and will be difficult to eliminate for life.
It is widely present in the blood, semen, vaginal secretions,
milk, cerebrospinal fluid and cerebral tissue fluids with neurological symptoms
of infected persons, among which blood, semen and vaginal secretions have the
highest concentrations.
The resistance to the external environment is weak, and the
effective disinfection method for hepatitis B virus is also effective for HIV
disinfection.
Infected persons have a long incubation period and a high
mortality rate.
The genome of the AIDS virus is more complex than any known
viral gene.
How Human Immunodeficiency Virus Development took place?
I. HIV Found
AIDS was first identified in the United States in the early 1980s
and was ignored by Reagan’s conservative government.
However, with the continuous work of the US Centers for
Disease Control and Prevention and knowledgeable doctors and scientists,
conclusive epidemiological data has been accumulated, showing that AIDS has a
certain infectious cause (etiology).
The infections caused by needles and blood transfusions have
gradually increased, and many scientists have begun investigating this
infectious agent.
II. Virus Naming
French virologist Luc Montagnier specializes in the relationship between
retroviruses and cancer at the Pasteur Institute in Paris.
His research team first obtained from a young man with
advanced Kaposi's sarcoma in 1983 A new retrovirus was isolated from the blood
and lymph node samples of people living with HIV / AIDS.
They found that this virus is different from human T cell
leukemia virus (HTLV) but a lentivirus (Lentivirus), they named it "Immune
Deficiency-Associated Virus" (IDAV).
On the other side of the Atlantic, Montagne’s collaborator
at the time, Robert Gallo, an American biomedical scientist at the National
Cancer Institute, and his staff also isolated new viruses from some cell lines
and named them Human III Cell Leukemia Virus-IIIB / H9 (HTLV-IIIB / H9).
Gallo's group first published a paper in the journal Science
in 1984 to demonstrate this Relationship between new viruses and AIDS.
In 1986, the name of the virus was unified as "Human
Immunodeficiency Virus" (HIV) to better reflect the nature of the virus
that causes immunodeficiency rather than cancer.
III. Virus Status
It has caused nearly 12 million deaths worldwide and more
than 30 million people became infected.
On July 25, 1986, the World Health Organization (WHO) issued
a communiqué, and the International Virus Taxonomy Committee decided to rename
HIV as human immunodeficiency virus (HIV).
In 2004, an estimated 35.9 to 44.3 million people worldwide
lived with human immunodeficiency virus, of which 4.3 to 6.4 million were new
infections, and 2.8 to 3.5 million died of AIDS.
These numbers are constantly increasing, and among them, East
Asia, Eastern Europe and Central Asia have the fastest growth.
The
worst-affected areas remain sub-Saharan Africa, followed by South and Southeast
Asia.
IV. Antibody Negative
Experts from the Department of Respiratory Medicine,
Infectious Medicine, and Pathology of Peking Union Medical College Hospital
jointly published the world's first case of HIV-negative AIDS combined with
pulmonary Kaposi's sarcoma in the Journal of Clinical Respiration in November
2017.
The imaging and pathological characteristics of pulmonary
Kaposi's sarcoma in this case are very typical. Peking Union Medical College's
first diagnosis of pulmonary Kaposi's sarcoma through pathology in China is of
groundbreaking significance and will help improve domestic doctors'
understanding of the disease.
V. What is the Survival Condition of Human immunodeficiency virus?
In vitro survival of HIV: It has extremely poor viability in vitro, is not resistant to
high temperatures, has low resistance, and is difficult to survive without the
human body.
At room temperature,
it can only survive for a few hours in the blood outside the body. It is sensitive
to heat and loses its activity after 30 minutes at 56 ℃, so it will not be infected in daily contact.
Inactivation method of HIV: When no stabilizer is added, the virus loses its activity
under freezing at -70 ℃.
While adding 35% sorbitol or 50% fetal bovine
serum, it remains active after freezing at -70 ℃ for 3 months.
It is also sensitive to disinfectants and detergents. 0.2%
sodium hypochlorite, 0.1% bleaching powder, 70% ethanol, 35% isopropyl alcohol,
50% ether, 0.3% H2O2 0.5% to Suer treatment for 5 minutes can inactivate
viruses. 1% NP-40 and 0.5% triton-X-100 can inactivate the virus and retain
antigenicity.
Strong resistance to ultraviolet rays and gamma rays
The International Health Organization recommends heating the
inactivated HIV at 100 ° C for 20 minutes. The effect is ideal.
The
disinfection of HIV is mainly aimed at medical supplies and living places
contaminated by the blood and body fluids of people infected with HIV and AIDS
patients. For example, accessories, gauze, clothing, etc.
For the disinfection of HIV, an appropriate physical method
or chemical method can be selected according to the disinfected items. Items
that need to be reused can be sterilized by boiling or high-pressure steam.
Items that should not be boiled can be disinfected with 2% glutaraldehyde and
75% alcohol.
Humoral survival of HIV: At room temperature, HIV can survive for 15 days in a
laboratory-controlled tissue culture fluid environment.
Some research institutes have proved that the survival time
of HIV in isolated blood depends on the content of virus in the isolated blood.
Blood with a high
content of virus can still be viable even if it is left at room temperature for
96 hours without drying.
Even with a drop of blood at the tip of a needle, if fresh
lymphocytes are encountered, HIV can still replicate in it and can still
spread.
Blood with low virus content loses its vitality after 2 hours
of natural drying out.
While blood with high virus content, even after drying for
2-4 hours, once placed in the culture medium, it can still enter lymphocytes
and continue to replicate . But these situations are limited to the laboratory
environment.
According to the American CDC report, even in a laboratory
environment, viruses used in the laboratory for much higher concentrations than
human blood and body fluids showed a 99% reduction in activity after drying for
several hours.
Therefore, with the exception of the laboratory environment, the
risk of infection with HIV-containing ex vivo blood is almost zero.
HIV cannot survive in the air, water and food, and these
viruses will quickly die outside, even in blood and other body fluids
containing HIV.
Not in a laboratory environment or in a closed environment
(such as syringes and needles), HIV cannot maintain activity. It must be
pointed out that in the residual blood of used injection needles.
HIV can survive for a relatively long time, and the needle
can directly enter the blood of the human body. Therefore, used injection
needles are very dangerous for HIV infection.
Used injections, the needle must never be reused. Relevant
scientific research departments in the United States have obtained the results
of nearly a million special-case exposure experiments excluding a clear
transmission route: less than one in ten thousand cases of infection.
What is the Mode of Infection from HIV (Human Immunodeficiency Virus)?
Way for spreading of HIV: HIV-infected persons are the source
of infection, and HIV has been isolated from blood, semen, vaginal fluid, and
milk.
Shaking hands, hugging, kissing, swimming, mosquito bites,
sharing tableware, coughing or sneezing, daily contact, etc. will not spread.
What are the 3 Main Modes of HIV Human Immunodeficiency Virus Transmission?
Sexual contact transmission
HIV exists in the semen and vaginal secretions of infected
persons. Sexual behavior can easily cause subtle skin and mucous membrane
damage, and the virus can enter the blood through the damage and become
infected.
Whether it is same-sex or heterosexual sexual contact will lead to
the spread of AIDS. There are a lot of viruses in the semen or vaginal
secretions of people with AIDS.
During sexual activity (including vaginal sex,
anal sex and oral sex), due to the friction of the sexual intercourse site, it
is easy to cause slight damage to the genital mucosa.
At this time, the
virus will Take advantage of it and enter the blood of uninfected people.
It is worth mentioning
that because the rectal wall is more likely to break than the vaginal wall, the
risk of anal sex is greater than that of vaginal sex.
Blood spread
Blood or blood products containing HIV, intravenous drug use,
tissues and organs of infected persons or patients are all at risk of
infection.
Mother-to-child transmission
Women infected with HIV can also pass the virus to the fetus
during pregnancy and childbirth, and infected mothers can also pass the virus
to breast-feeding children through breastfeeding.
Pathogenic mechanism
HIV selectively invades CD4 molecules, mainly T4 lymphocytes,
monocytes, and dendritic cells. The CD4 molecule on the cell surface is an HIV
receptor.
After binding to the CD4 on the cell membrane through the HIV
envelope protein gp120, the conformation of gp120 changes to expose gp41. At
the same time, gp120-CD4 binds to the chemokine CXCR4 or CXCR5 on the surface
of the target cell to form CD4-gp120. -CXCR4 / CXCR5 trimolecular complex.
gp41 acts as a bridge in it, using its own hydrophobic effect
to mediate the fusion of viral capsule and cell membrane.
Eventually the cells
are destroyed.
The mechanism is not fully understood and may work in the
following ways:
1. As HIV envelope proteins are inserted into cells or virus
buds are released, cell membrane permeability is increased and osmotic lysis
occurs.
2. The CD-gp120 complex in the infected cells is fused with
the membranes of organelles (such as Golgi apparatus, etc.) to dissolve them,
leading to the rapid death of infected cells.
3. Unincorporated DNA accumulation during HIV infection, or
inhibition of cellular proteins, leads to HIV killing of cells.
4. The gp120 expressed by HIV-infected cells can bind to CD4
on the uninfected cell membrane, fuse under the action of gp41 to form
multinucleated giant cells and dissolve to death.
5. HIV-infected cell membrane virus antigens bind to specific
antibodies and lyse cells by activating complement or mediating ADCC effects.
6. HIV induces autoimmunity. For example, gp41 has a homology
region with MHC class II molecules on the membrane of T4 cells. Anti-gp41
antibodies can cross-react with such lymphocytes, leading to cell destruction.
7. Programmed cell death: Apoptosis can be activated during
the onset of AIDS. For example, gp120 of HIV binds to CD4 receptor. It directly
activates the apoptosis of infected cells.
Even the envelope antigen expressed
by HIV-infected T cells can activate normal T cells, which indirectly causes a
large amount of apoptotic CD + 4 cells to be destroyed by cross-linking of CD4
molecules on the cell surface, resulting in severe immune defects centered on
T4 cell defects.
The patient's main manifestations: peripheral lymphocyte
reduction, T4 / T8 ratio configuration, the response to phytohemagglutinin and
certain antigens disappears, delayed allergic reaction decreases, the activity
of NK cells and macrophages decreases, IL2, interferon gamma Reduces cytokine
synthesis.
Early in the course of disease, because B cells are in a
polyclonal activation state, the serum lg level in patients often increases.
As the disease progresses, the function of B cells to produce
antibodies to various antigens is also directly and indirectly affected.
People with AIDS suffer from severe immunodeficiency and
often have severe opportunistic infections.
Common bacteria (mycobacterium intracellular avian complex,
MAI), protozoa (pneumocystis carinii, toxoplasma) and fungi (candida albicans,
Cryptococcus neoformans), viruses (cytomegalovirus, herpes simplex virus,
hepatitis B virus), which eventually lead to uncontrollable death.
In other cases, Kaposis sarcoma or malignant lymphoma can
occur.
In addition, HIV in infected mononuclear macrophages is
proliferated at a low level without causing lesions, but damages its immune
function, can spread the virus throughout the body, and causes interstitial
pneumonia and subacute encephalitis.
After entering the human body, the AIDS virus was first
engulfed by macrophages, but the AIDS virus quickly changed the acidic
environment in certain parts of the macrophages, creating conditions suitable
for its survival, and then entered a large number of T-CD4 lymphocytes.
Reproduction eventually destroys the latter immune cells
completely.
HIV infection can stimulate the body to produce antibodies to
envelope proteins (Gp120, Gp41) and core proteins (P24).
Low levels of
antiviral neutralizing antibodies have been detected in the serum of HIV
carriers and AIDS patients.
Among them, AIDS patients have the lowest levels
and HIV carriers have the highest, indicating that the antibodies have
protective effects in the body.
However, the antibody should not be in contact with the virus
remaining in the mononuclear macrophage, and the HIV envelope protein is
susceptible to antigenic mutation, and the original antibody will lose its
function, so that the neutralizing antibody cannot play its due role.
During the latent infection phase, HIV provirus is integrated
into the host cell genome, so HIV is not recognized by the immune system, so it
cannot be cleared by relying only on its own immune function.
Is there any Hiding place of HIV or Human Immunodeficiency Virus?
For a long time, the medical community discovered during
clinical treatment that all HIV carriers receiving intensive treatment
reappeared soon after the treatment was stopped, and inferred that not only the
HIV hiding place exists in the body of the infected person The place, and the
body's immune system is difficult to effectively control it.
Intestinal lymph nodes
After further research, scientists have found that T-CD8
lymphocytes (cytotoxin T lymphocytes) in the intestinal lymph nodes are less
active. Such killer lymphocytes in other tissues can usually destroy infected
cells and control the virus.
But the lymphocytes in the intestinal lymph nodes
lack this ability, which causes the HIV to hide in it and gradually spread to
other organs, making the disease worse.
Subsequently, the researchers confirmed that it is TGF-β
cytokine that causes T-CD8 lymphocyte dysfunction in intestinal lymph nodes,
and it is precisely that it inhibits the activity of T-CD8 lymphocytes, leading
to premature aging.
French scientists say that their research provides new ideas
for the complete defeat of AIDS, such as inhibiting TGF-β cytokines, repairing
T-CD8 lymphocytes with impaired function, and strengthening treatment for
intestinal lymph nodes. This will also be their next main subject.
Memory T cells
Memory T cells are a hiding place for some HIV viruses. When
the cell is alive, the virus is alive. The cell dies and the virus is released,
infecting more healthy cells.
Memory T cells, a type of human immune cell, although it is a
hiding place for some HIV viruses, can also limit the activity of these viruses
to a certain extent.
CD4 cells
HIV attaches to CD4 cells, reenters CD4 cells and infects it.
When a person is infected with HIV, the virus creates more virus cells in the
immune system of the infected person, turning it into a factory for making
viruses.
HIV will continue to
replicate, CD4 cells will be destroyed, and the immune system will create new
immune cells to replace dead immune cells, but the newly created immune cells
will not be immune to HIV infection.
Even if people living
with HIV feel good and have no symptoms, at this time, hundreds of millions of
CD4 cells may have been destroyed.
CD4 is the most important immune cell. Once an infected
person loses a large number of CD4 cells, the entire immune system will be
fatally hit, and will lose resistance to various diseases.
What is the Detection Method of HIV?
The method for detecting viral antigens and antibodies in
body fluids of HIV-infected persons is convenient to operate and easy to
popularize and apply, in which antibody detection is particularly common.
However, the status and importance of HIv P24 antigen and viral genes in the
detection of HIV infection have also received increasing attention.
Antibody detection
HIV antibodies in serum are an indirect indicator of HIV
infection.
According to its main scope of application, existing HIV
antibody detection methods can be divided into screening tests and confirmation
tests.
HIV Confirming Reagents
Western blot (WB) is the most commonly used to confirm the
positive serum of the screening test.
Because the method has a relatively long window period, a
slightly lower sensitivity and a high cost, it is only suitable as a
confirmation experiment.
With the improvement of the sensitivity of the third and
fourth generation HIV diagnostic reagents, WB has been unable to meet its
requirements for confirmation experiments.
Another type of screening confirmation reagent approved by
the FDA is the immunofluorescence test (IFA).
IFA is cheaper than WB, and the
operation is relatively simple. The whole process can be completed in 1-1.5
hours.
The main disadvantage of this method is that it requires
expensive fluorescence detectors and experienced professionals to observe the
evaluation results, and the experimental results cannot be stored for a long
time.
The FDA recommends that when a final result is released to a
blood donor who cannot be determined by WB, the negative or positive of IFA
shall prevail, but it shall not be regarded as a standard for blood
qualification.
Screening Test for HIV
The screening test is mainly used for screening blood donors,
so it requires simple operation, low cost, and sensitivity and specificity.
In
2012, the main screening method in the world was still ELISA, as well as a few
particle agglutination reagents and rapid ELISA reagents.
ELISA has high sensitivity and specificity, and is easy to
operate. It only needs to be equipped with a microplate reader and a plate
washer in the laboratory.
It is especially suitable for large-scale screening
in the laboratory.
The particle agglutination experiment is another simple and
convenient, low-cost detection method.
The results of this method can be judged by the naked eye,
and the sensitivity is very high.
It is especially suitable for developing countries or a large
number of blood donors. Sex is poor.
Dot-blot assay developed in the late 1980s is a rapid ELISA
(Rapid ELISA) method. This method is extremely simple to operate and the
process is short.
The entire process is mostly within 5-10 minutes or even 3
minutes. It can be ended, but this method is much more expensive than ELISA and
particle agglutination reagents.
Human immunodeficiency virus antibody oral mucosal exudate
detection kit (colloidal gold method) belongs to the category of lateral
immunochromatography (gold immunoassay).
Based on immunochromatography technology, the results can be
read manually and visually.
A rapid diagnostic
reagent with qualitative test results for the detection of HIV-1 and HIV-2
antibodies in oral mucosal exudate samples.
It can be used for the initial
screening of patients with voluntary consultation and testing, unwilling to
collect blood and dizzy needles.
This method is suitable for the initial
screening test. Anyone who is tested positive by this reagent needs further
screening confirmation.
[HIV negative] means that no HIV antibody can be detected
from the human body, and the negative symbol is indicated by (-).
It cannot be said that
there is no HIV infection, depending on when it is detected.
During the window period, the infected person has not yet
produced HIV antibodies, or sufficient HIV antibodies have not been produced.
At this time, the HIV test is negative.
Testing after the period can exclude
the possibility of HIV infection.
[HIV positive] indicates that HIV antibody has been detected
from the human body, and the positive symbol is indicated by (+).
What are the Uncertain factors of HIV Test Results?
Infection is still in the window period: The time from HIV
entering the body to detection is not long enough, so the serum has not formed
a typical antibody response.
AIDS progresses to end stage, antibody levels drop.
Cross-reactions of other non-viral protein antibodies. In
autoimmune diseases, certain malignant diseases, pregnancy, blood transfusions,
or organ transplants, the body can produce some antibodies, and the response is
similar to that caused by the HIVP24 core protein antibody
Antigen Detection
Pathogen detection mainly refers to the direct detection of
viruses or viral genes from host specimens by methods such as virus isolation
and culture, electron microscope morphological observation, virus antigen
detection, and gene determination.
Because the first two methods are difficult which require
special equipment and professional technicians. Therefore, only antigen
detection and RT-PCR (reverse transcription-PCR) can be used for clinical
diagnosis.
HIV-1P24 antigen test can be used for auxiliary diagnosis of
HIV-1 antibody indefinite or window period.
Eearly auxiliary differential diagnosis of infants born to HIV-1
antibody-positive mothers.
Fourth-generation HIV-1 antigen / antibody ELISA reagent test
is positive However, HIV-1 antibody confirmed negative diagnosis. P24 antigen
detection generally uses ELISA double antibody sandwich method reagents.
The
reagents must be registered and approved by SDA. Within the validity period,
the positive results must be confirmed by neutralization test according to the
reagent instructions.
The sensitivity of the HIV-1P24 antigen test is 30-90%.
This result is only used as a supplementary diagnostic basis for HIV infection
and cannot be diagnosed accordingly.
A negative HIV-1 P24 antigen test only means that there is no
response in this test, and HIV infection cannot be ruled out. Generally it is not used as a routine
diagnostic item in clinical practice.
Nucleic Acid Detection
HIV nucleic acid testing can be used for auxiliary diagnosis
of HIV infection, monitoring of disease course, guiding treatment plan and
judgment of curative effect, predicting disease progress, etc.
Commonly used HIV viral load detection methods include
reverse transcription PCR (RT-PCR), nucleic acid sequence amplification experiment
(NASBA), branched DNA hybridization experiment (bDNA), and real-time
fluorescent quantitative PCR technology.
It is worth noting
that each HIVRNA quantification system has its minimum detection limit, that
is, the lowest copy number or international unit that can be measured.
When the
RNA is not detected during quantitative detection, it does not mean that the
sample does not contain viral RNA, so the HIV nucleic acid is qualitative.
If
the test is negative, only the negative result of this experiment can be
reported, but HIV infection cannot be ruled out.
HIV nucleic acid test is
positive, it can be used as an auxiliary indicator for diagnosis of HIV
infection, and cannot be used alone for the diagnosis of HIV infection.
When reporting HIV nucleic acid quantitative test results,
report the results according to the instrument reading, indicating the
experimental method used, the type of sample, and the amount of the sample.
When the measurement result is less than the minimum
detection limit, indicate the minimum detection limit level.
Qualitative detection of HIV nucleic acid can also be used as
an auxiliary diagnosis of HIV infection, and it can be used in basic research
such as analysis of HIV genotypes and mutations.
Usually PCR or RT-PCR technology
is used, and the amplification reagents commonly used in molecular biology
laboratories are used.
The primers can be
from the literature or designed by themselves. They should cover all or common
strains as much as possible. Compound primers can also be used.
When reporting qualitative test results, the reaction
conditions and primer sequences used should be noted. In addition, using the
high sensitivity of nucleic acid detection methods, using collective nucleic
acid amplification detection techniques and methods, collective nucleic acid
detection can be performed on samples that are highly suspected to be infected
and antibody-negative samples can detect window-infected patients in a timely
manner.
This method is more cost-effective than nucleic acid detection in a
single sample.
Training method
The common method is the co-culture method, that is, the
mononuclear cells are isolated from the peripheral blood of normal people, stimulated
and cultured with PHA.
These cells are then added to the diagnosis of patients'
mononuclear cells and the study of AIDS.
The lymphocytes in the patient's own periphery or bone marrow
are stimulated by PHA for 48 to 72 hours for in vitro culture (IL2 is added to
the culture medium) for 1 to 2 weeks, the virus proliferation can be released
outside the cell.
The cells are fused into multinucleated giant cells. The cell
ruptured and died.
Passive lymphocyte lines such as HT-H9 and Molt-4 cells can
also be used for isolation and passage.
HIV animals have a narrow range of infections, and only
chimpanzees and gibbons are commonly used for experiments.
Infect chimpanzees
with HIV-infected or cell-free HIV filtrates, or infuse HIV-infected chimpanzee
blood to normal chimpanzees, and the infection is successful.
Continue to isolate HIV in the blood and lymph fluid for 8
months, after 3 to 5 weeks Find HIV-specific antibodies and continue to
maintain a certain level. But neither chimpanzee nor gibbon infected after the
disease.
What are the main Symptoms of HIV (Human Immunodeficiency Virus)?
Suspected symptoms
Common symptoms
Persistent extensive lymphadenopathy, especially cervical,
axillary, and groin lymph nodes.
Lymph node enlargement is about 1 cm in
diameter, hard, painless and mobile, and lasts more than three months.
1. Unexplained fever and night sweats for several weeks.
2. Severe fatigue that has been unexplainable for weeks.
3. Appetite loss, weight loss in more than 10% of original
weight within 2 months.
4. Chronic diarrhea of unknown cause has appeared for
several weeks, showing a watery pattern, more than 10 times a day.
5. Shortness of breath, dry cough for several weeks.
6. Flat and raised pink and purple-red spots appear on the
skin and mouth without pain or itching.
7. White spots appear in the pharynx and larynx. T
here are
scaly patches and itching in the male genitals.
Women have anal itching,
vaginal itching, and leucorrhea.
8. Headache and blurred vision.
When more than the above three symptoms and a history of
unclean sexual contact, should go to the hospital for examination.
The symptoms caused by the HIV virus are not specific. In
real life, there are many reasons that can cause the above symptoms.
You cannot
conclude that you have the HIV virus because your body has related symptoms.
Only a scientific "HIV antibody / antigen test" can draw a correct
conclusion.
Asymptomatic latent
Some people have been asymptomatic after HIV invaded the
body, and went directly to the asymptomatic period.
The length of AIDS
incubation period varies greatly between individuals, which may be related to
the type, intensity, quantity, infection route of the invading AIDS virus and the immune function, health
status, nutritional status, age, life and medical conditions, psychological
factors of the infected person.
It is generally 6-10 years, but about 5-15% of
people progress to AIDS within 2-3 years, called rapid progressers.
5% of patients whose immune function can maintain normal for
more than 12 years, Called long-term non-progressors.
Human damage
HIV not only makes it difficult for the body's immune system
to resist its invasion, but also makes it difficult for the development of
special therapeutic drugs and preventive vaccines.
HIV directly invades the
body's immune system and destroys the body's cellular and humoral immunity.
It
is mainly found in the body fluids of infected people and patients (such as
blood, semen, vaginal secretions, breast milk, etc.) and in many organs.
It can
be transmitted through HIV-containing body fluid exchange or organ
transplantation.
Erosion cell
HIV has been proven to be a T4-lymphocyte and neuroblast
virus. HIV enters the body's blood from a broken skin or mucous membrane, and
mainly attacks and destroys the target cell T4 lymphocytes (T4 lymphocytes play
a central regulatory role in the cellular immune system, which can promote B
cells to produce antibodies), and T4 cells are lost The original normal immune
function.
When almost all of the T4 cells that activate the immune
response are eliminated by HIV, the number of T4 cell suppressor cells increase
dramatically.
On the contrary, the number of T4 cells in the patient's body
decreases suddenly, which leads to the total failure of the patient's immune
function, creating an extremely extreme favorable conditions.
HIV has an affinity for nerve cells, can invade the nervous
system, cause the destruction of brain tissue, or cause a variety of central
nervous system lesions due to secondary conditioned infection.
Ignore antibodies
After entering the human body, the AIDS virus was first
engulfed by macrophages, but the AIDS virus quickly changed the acidic
environment in certain parts of the macrophages, creating conditions suitable
for its survival, and then entered a large number of T-CD4 lymphocytes.
Reproduction
eventually destroys the latter immune cells completely.
HIV envelope proteins are prone to antigenic mutations, and
the original antibodies lose their effect, making neutralizing antibodies
unable to play their due role.
During the latent infection stage, the HIV previrus
integrates into the host cell's genome.
The immune system ignores HIV and does not recognize it by
the immune system. Autoimmunity cannot be eliminated.
The human immune system has the ability to suppress early
HIV. Recent studies have shown that most newly infected patients develop
neutralizing antibodies.
These antibodies are droplet-shaped blood proteins
that attach to the virus. If they face only one target, they allow patients to
defend themselves.
But the problem is that HIV has the ability to mutate. Its
ability to disguise itself is enough to escape the pressure of antibodies.
HIV
will eventually disintegrate the immune system and deplete it. Some AIDS
viruses can mutate some of the outer protein.
After the mutation, an enzyme may attach a sugar molecule to
it and interfere with the attack of the antibody. But this "glycan
shield" phenomenon cannot be observed in all cases.
Other viruses mutate parts of the outer layer of proteins
that are directly attached by neutralizing antibodies.
HIV-1 invades immune system cells called T-lymphocytes,
"hijacks" the "molecular machinery" of T-lymphocytes to
make more HIV-1. Then it ultimately destroys host cells-which makes infected
people more vulnerable to other lethal diseases Impact of the disease.
However, T lymphocytes are not easy to be hit by. Within
their anti-virus defense system is a class of proteins called APOBEC3s, which
has the ability to prevent HIV-1 from replicating itself.
However, HIV-1 also has an anti-defense mechanism-a protein
called virion infection factor (Vif), which can cause T lymphocytes to destroy
their own APOBEC3s.
Helps develop cancer
HIV is similar to other retroviruses. When reverse
transcriptase synthesizes DNA from viral RNA as a template and integrates the
viral DNA into the DNA of the host cell, the oncogenes carried by HIV can cause
the cancerous transformation of cells.
Especially, under the circumstance that
the cellular immunity is destroyed and the immune surveillance function is
lost, the change of cell carcinoma is easy to occur.
Take life
The survival time of AIDS patients has a great relationship
with the type of subtype virus they are infected with.
The average survival time of AIDS patients varies greatly
depending on the type of subtype infected, although the number of viruses
infected by these subjects is basically the same.
The average survival time of those infected with subtype A
virus was 8.8 years, while the average survival time of those infected with
subtype D virus was reduced to 6.9 years.
The survival time of
those with mixed infection of subtype D and subtype A viruses was shorter. The
average is only 5.8 years.
What is going on about HIV Vaccine Development?
In September 2009, a medical trial supported by the US
military in Thailand found that an experimental vaccine can greatly reduce the
risk of contracting HIV.
For the first time, humans have received an AIDS
vaccine with a certain immune effect.
What are the Challenges in the development of an HIV-1 Vaccine?
- Extensive Viral class & sequence diversity
- Early establishment of latent viral reservoirs
- Immune correlates of protection unclear
- Viral evasion of humoral and cellular immune responses
- Anti-body responses typically type-specific
- No method exists to elicit broadly reactive neutralizing antibodies
- Attenuated viruses unsafe for human use
- Lack of small-animal model
- Little pharmaceutical interest
Clarification:
- Wide range of viruses and sequence diversity
- Early establishment of latent viral reservoirs
- Unclear immune-related protection
- Viral escape of humoral and cellular immune responses.
- Typical anti-body response
- No existing method to cause widespread reactive neutralizing antibodies
- The attenuated virus is not safe for human use
- Lack of small animal models
What are the Challenges in the Development of HIV-1 vaccine?
Little Medical Gains
Scientists performed a nearly full-length genome analysis of
HIV-1 on a Burmese long-distance trucker in the border area between China and
Myanmar, and found that the HIV-1 CRF01_AE / B / C recombinant virus strain was
more than the HIV recombinant virus reported from Myanmar 12 years ago. The
strain is more complicated.
"Human immunodeficiency virus" (English
abbreviation HIV) can destroy the body's immune system after invading the body,
causing the body to produce a variety of incurable infections and tumors, which
eventually lead to death.
It has been confirmed that HIV is divided into two types:
HIV-1 And HIV-2. Worldwide, HIV-1 infection predominates.
What is the Research Progress regarding Human Immunodeficiency Virus - HIV?
HIV Origin Doubt
With the continuous deepening of HIV research, people have
isolated monkey immunodeficiency virus similar to HIV, referred to as SIV, in
different primates.
SIV and HIV are basically the same in gene size and
composition, but SIV does not cause any disease in its natural host monkey.
However, when SIV isolated from a natural host is inoculated
into an unnatural host monkey, it will cause symptoms similar to human
immunodeficiency.
For example, after inoculating SIVsm isolated from Florida
rhesus monkeys to rhesus monkeys, after a clinical incubation period, they will
produce clinical symptoms similar to AIDS, such as diarrhea, weight loss, and
imbalanced CD4 and CD8 cells.
It has also been found that the genetic variation of viruses
isolated from wild African green monkeys is very large, and this variation is
consistent with the evolutionary relationship of different species of monkeys,
suggesting that monkey immunodeficiency viruses have co-evolved in monkeys for
quite a long time.
All these studies
suggest that human HIV may be transmitted from monkeys to humans in the form of
cross-transmission between different species.
Until the early 1990s, Gao Feng and Hahn and others in the
study of the epidemic of HIV-2 in remote areas of Africa provided a more direct
clue to the origin of HIV, which further proved that Type B HIV originated in
monkey HIV.
The most important
finding of the study was the isolation of a virus (HIV-2 / FO784) similar to
monkey immunodeficiency diseases SIVsm and SIVmac from an HIV-2 healthy
carrier.
In evolutionary
analysis, due to the high homology between FO784 and SIVsm / mac, they cannot
be distinguished from each other in the evolution tree, which strongly suggests
that human HIV originated from monkey immunodeficiency virus.
This was not only confirmed by later similar experiments, but
also a large number of epidemiological results also supported this conclusion.
i.
About
30% of wild Florida monkeys are infected with SIVsm. A large proportion of wild
monkeys carry SIV, which directly proves that the Florida long-tailed monkey is
the natural host of SIVsm.
ii.
SIVsm
and HIV-2 co-exist in the same geographic area in several countries in western
Africa. And people living together in West Africa have close contact with the
Florida vervet monkeys. For example, people often hunt Florida vervet monkeys
as pets or food.
iii.
Florida
cynomolgus monkeys infected with SIVsm do not produce any clinical symptoms,
but when SIVsm is inoculated into rhesus monkeys, it produces immune deficiency
syndrome similar to humans. All of this shows that SIVsm and Florida monkeys
have formed a symbiotic relationship, that is, Florida monkeys have become the
natural host of SIVsm, and no longer have any clinical symptoms due to SIVsm
infection. However, when SIVsm infects a new host, it causes clinical
manifestations not found in its natural host. As with SIVsm infected rhesus
monkeys, when SIVsm infects a new host human, immunodeficiency syndrome
develops in the infected person. Therefore, human immunodeficiency syndrome is
actually an animal infectious disease, that is, a disease that is transmitted
from animals to humans in the natural state.
Of course, the most complete proof should be to obtain a
large amount of epidemiological and genetic evidence for the direct
transmission of SIVsm from the Florida monkey.
However, under the premise that this information is almost
impossible, the isolation of SIV-like virus from humans provides the most
convincing evidence that HIV originated from monkey HIV.
The subtypes D and E of HIV-2 are closely related to their
corresponding SIVs, and form the same group with the corresponding SIVs in
evolutionary analysis, but they cannot be distinguished from SIVs.
This shows
that at least D and E are caused by the second independent transmission from
monkey to human.
At least 5 different HIV-2 subtypes have been discovered in
2012, suggesting that this transmission between different species may have
occurred at least 5 times for HIV-2.
Not long ago, in an accident, an experimenter was infected
with SIV because he did not strictly observe the experimental operation
regulations.
In the follow-up investigation for more than two years, the
virus and corresponding antibodies were successfully detected from the
experimenter's body, indicating that the experimenter has been infected by SIV.
The accident directly demonstrated the possibility of the transmission of
immunodeficiency virus from monkeys to humans.
Through the above research, we have a relatively clear
conclusion on the origin of HIV-2. However, the origin of HIV-1 has always been
an unsolved mystery.
Although it is widely believed that HIV-1 originates from
similar monkey viruses as HIV-2, clear evidence has been lacking.
Although a virus similar to human HIV-1 (SIVcpz) has been
successfully isolated in chimpanzees, the genetic material between the two is
very different.
Unlike the relationship between HIV-2 and SIVsm / mac, in the
analysis of genetic evolution, HIV-1 does not form a closely related group with
any SIVcpz. In addition, under natural conditions, the infection rate of
chimpanzees is very low.
Of the hundreds of screened chimpanzees, only four were found
to be serologically positive, which is well below the natural infection rate of
SIVsm.
There are two views on the origin of HIV-l:
One view is that human HIV originated in SIVcpz, but SIVcpz
samples that are closely related to HIV-1 have not yet been collected. However,
due to the very low natural infection rate of chimpanzees, this is unlikely.
Another view is that humans and chimpanzees share a common
source of HIV infection.
However, the latest
experimental results show that human HIV type I virus actually originated from
chimpanzees in Africa.
By analyzing the
mitochondria of chimpanzee hosts and the SIV virus gene sequences they
infected, the study proved that two of the four types of chimpanzees living in
Africa were infected by their corresponding SIVs.
All the current
popular HlV-l originated from only one type of chimpanzee living in Central and
West African countries.
At the same time, in July 2009, scientists discovered
that HIV can cause chimpanzees to die in large numbers.
A scientific research result of a team of young professor Hou
Wei from the Wuhan University School of Basic Medicine and Professor Huo Wenzhe
from the Animal Experiment Center of Wuhan University was published in August
in the famous American academic journal "Lymphocyte Biology". The
study found that a type of T lymphocyte that expresses the CD56 molecule has an
anti-HIV infection effect.
After three years of research, it was first discovered that
the secretion in the culture medium of "T-lymphocytes expressing
CD56" can inhibit HIV infection and replication, and this activity has a
broad spectrum, which can inhibit HIV stored in the laboratory. Strains can
also inhibit clinically isolated HIV strains.
Although the secretions in the culture solution have little
effect on the co-receptors of HIV entering the cells, they can enhance the
effect of interferon regulatory factors, thereby causing macrophages to function
and "fight against" HIV.
How HIV has spread in the population at an alarming rate in
the past decade has not been clearly answered. However, due to the continuous
development of the economy and the development of transportation, population
mobility has greatly increased, and changes in living habits have undoubtedly
played an important role in the epidemic of AIDS.
Hijack cell
In January 2014, Huang Zhiwei's research group at the School
of Life Sciences of Harbin Institute of Technology revealed the structure of
the HIV virion factor Vif for the first time in the world.
It clarified how Vif
"hijacks" the molecular mechanism of human immune cells, and provided
a structure for the development of new AIDS drugs basis.
This research is of
great significance and important scientific application value for mankind to
finally overcome AIDS.
As a vital influencing factor in the nine major genes of HIV,
Vif is considered by the academic community to be evolved against human evolution
during the transmission of HIV. It degrades the virus in human immune cells by
"hijacking" the protein degradation system in human immune cells.
Restriction factor members of the APOBEC3 family, thus
evading immune cells' recognition and defense against HIV. But for a long time,
no progress has been made in the analysis of the atomic level structure of Vif
itself or its functional complexes.
In the research, Huang Zhiwei's research group focused on the
"stubborn disease" of Vif, focusing on the analysis of the structure
of the five-component complex of Vif, and described in detail how Vif
"hijacks" the human CBF-β and CUL5 E3 ligase complex molecular
mechanism.
This study analyzes the structural characteristics of HIV and
understands how HIV is combined with people, which provides the possibility of
further solving the problem of AIDS treatment.
According to the "key-on-key" rule, the study has
also opened up a new path for future AIDS treatment from a
"cocktail-style" mixed drug approach to the design of targeted
therapeutic drugs.
The research paper has been published online in the journal
Nature, and was featured in the "News and Perspectives" column of the
journal Nature as a featured article.
Virus antibody
The National Institute of Infectious Diseases (NICD) in South
Africa says scientists are looking for antibodies that can kill different
strains of the virus (HIV) and are expected to develop AIDS vaccines.
Morris, director of the NICD's virology department, said
scientists took a woman's blood sample to study her response to HIV infection
and isolated the antibodies she produced.
The human body's response to HIV is to produce antibodies
against the virus. In most cases, antibodies cannot neutralize or kill
different virus strains, but a few broad-spectrum neutralizing antibodies can
pass through the protective layer around HIV to kill the virus.
Moore, a scientist involved in the research, said that
researchers have been able to replicate antibodies and will test whether they
can exert immune functions without human infection.
She said: "We will carry out the monkey experiment
first, and then we will start the human experiment." The human experiment will
take at least 2 years.
Activation latency
Scientists from the Gladstone Institute report in the journal
Science that they have found a new way to expose latent HIV to themselves,
which may help overcome one of the biggest obstacles to finding a cure for HIV
infection.
They found that without increasing the average level of HIV gene
expression, as long as the random activity (noise) associated with HIV gene
expression is increased, latent HIV can be reactivated.
When HIV infects
immune cells, it inserts its own genetic material into the DNA of infected
cells. In most cases, the machinery of immune cells copies the genetic material
of the virus, eventually resulting in the expression of all the elements needed
to generate more viruses. New viruses are released from infected cells and will
spread to other immune cells in the body.
However, in some cases, HIV expression enters a waiting mode,
and the virus in the infected immune cells enters a latent state. This means
that a small percentage of HIV is hidden in infected cells, and even the most
effective drugs cannot reach them.
What is the Procedure to Remove Human Immunodeficiency Virus - HIV form Human Cells?
In July 2014, researchers in Philadelphia, the United States,
discovered a way to completely remove HIV from human cells.
In a study published in the National Science Academic
Progress Journal, the researchers first called a method called the nuclease's
DNA cleavage enzyme binds to a target strand called ribonucleic acid, and then
the combination begins to hunt down and eventually remove the HIV-1 viral
genome.
After the removal, the cell's genetic repair program began to
take over the entire process, welding the damaged ends together, resulting in a
virus-free cell.
Because the HIV-1 virus cannot be cleared by the immune
system, the disease can only be cured by removing the virus. These molecular
weapons can also be used as vaccines. Cells armed with nuclease-ribonucleic
acid have been shown to be immune to HIV infection.
The laboratory used a 20-nucleotide chain-directed
ribonucleic acid to target the HIV-1 virus, and then used a DNA cleaving enzyme
called Cas9 to modify the human genome. Researchers have come up with different
strategies to apply to preclinical research, hoping to eliminate every HIV-1
virus in patients in order to cure AIDS.
Cure Case
On March 6, 2019, it was reported that a man with HIV in the
British capital received a bone marrow transplant three years ago,
"inheriting" the genetic mutation of the donor. He also did not detect
HIV for more than 18 months, and is expected to become a follow-up patient
"After the second successfully cured AIDS patient.
Author's Bio
 |
| Dr. Shawna Reason |
Education: MBBS, MD
Occupation: Medical Doctor / Virologist
Specialization: Medical Science, Micro Biology / Virology, Natural Treatment
Experience: 15 Years as a Medical Practitioner
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