Virus HIV- AIDS (human immunodeficiency viruses)

2021-08-14 11:18 PM

The genital tract is one of the main routes by which the HIV virus is transmitted from an HIV-infected patient to a healthy person

HIV virus (including HIV1 and HIV2) belongs to the family Retroviridae, genus Lentivirus. These viruses have a spherical, enveloped shape, a virus particle size of 80-100 nm in diameter, and a genome containing single-stranded RNA. Their nucleic acid (RNA) replication produces double-stranded cDNA (complementary DNA) mediated by the enzyme reverse transcriptase. The formation of the proviral form in the chromosomes of host cells is a required step in their development cycle.

Structural features

Under the electron microscope, the virus has a spherical shape, composed of an outer shell and an inner capsid core. The viral envelope is made up of 72 spikes that are the glycoprotein 120 (gp120) of the outer envelope, which is a receptor that binds to the cell's CD4+ receptor and a transmembrane protein glycoprotein 41 (gp 41). The core of the globular virus contains the structural proteins of the Gag gene, the capsid contains two identical RNA molecules and the enzyme DNA polymerase. The detailed structure of the virus and the HIV genome is shown below.

Image. The image illustrates the complete structure of the HIV virus

The HIV genome has a size of 9.8kb (kilobase), the gene coding for HIV has 3 large segments, which is the gag gene that encodes for the synthesis of structural proteins of the viral core, the pol gene that encodes for viral replication. formation of viral enzyme proteins (integrase, reverse transcriptase/RNase, protease) and the env gene fragment that encodes the formation of viral envelope glycoproteins (gp 120, gp 41). Many small gene fragments code for proteins that play a role in viral infection and growth in cells.

Table of  HIV proteins and their function

Resistance properties

HIV is inactivated at 56 - 60 0 C for about 30 minutes, it is also inactivated with common bactericidal chemicals such as 0.5% sodium hypochlorite solution, 70% ethanol alcohol, and povidone-iodine, at pH < 6 or > 10 inactivates HIV1 in about 10 minutes. In virus cultures at room temperature, free HIV can be detected for up to 15 days, at 37 0 C, up to 11 days.

The biological cycle of HIV in the cell

To enter cells, HIV gp120 binds to cell receptors: the CD4+ molecule and the CCR5 receptor to enter the cell. In the cytoplasm of the cell, single-stranded viral RNA is reverse transcribed to become double-stranded DNA mediated by reverse transcriptase, and the resulting double-stranded DNA is transferred to the cell nucleus and incorporated into the cell's chromosomes. , called a provirus is mediated by the enzyme integrase. The proviral DNA is the template for the creation of new viral RNA and the messenger RNA for viral protein synthesis.

New virus assembly and formation occur in the cell membrane. Here the newly formed viral RNA is encapsulated in the proteins of the capsid core. The capsid then acquires an envelope as the virus particle passes through the cell membrane by means of a gradual ejection of the virus particle such as budding.

The process of viral replication in a cell is summarized in the following diagram:

Image. Diagram illustrating the HIV replication cycle in cells

Viral growth in cell culture produces a cytopathological effect depending on the isolates, many strains produce syncytium formation and induce cell death, however, some strains do not create this image. The cytopathogenic properties are used to distinguish the biological subtypes of HIV1.  

Mechanism of immunodeficiency and epidemiology

Mechanism of immunodeficiency due to HIV

Immunodeficiency due to HIV infection is primarily due to a decrease in the population of CD4 surface-carrying T lymphocytes (CD4+ cells), the destruction of which this decreased cell population is associated.

The direct pathological cellular effects of the virus and its proteins on CD4+ cells include Cell destruction, Stem cell effects, Effects on cytokine production, Effects on cell charge, Increased fragility of cells.

Cellular HIV infection induces programmed cell death (apoptosis).

Cytotoxicity by binding of gp120 to normal CD4+ cells: ADCC effect, cytotoxic T lymphocytes (CTL).

Immunosuppressive effects of immune complexes and viral proteins (gp120, gp41, Tat).

Cytotoxic effect against CD4 (including CD4+ cells and CD8+ cells).

CD8+ cell inhibitory factors.

Autoantibodies against CD4+ cells.

Cytokine-induced destruction of CD4+ cells.

Epidemiology of HIV infection

Immunodeficiency syndrome was first found in 1981 in injecting drug users. 1983 L. Montagnier in France isolated the virus and called it LAV (lymphadenopathy-associated virus), R. Gallo in the United States at the same time also cultured the virus from immunocompromised patients and analyzed its biology. Because of its molecular biology and naming the virus HTLV III (Human T cell leukemia virus type III), the viruses are almost identical. In 1986, the International Committee on Virus Nomenclature agreed to name these viruses as HIV (Human immunodeficiency virus).

Currently, there are about 30 million people infected with HIV worldwide, there are two types of viruses that cause disease, HIV1, and HIV2. HIV1 causes diseases found all over the world, while HIV2 is found only in a few parts of West Africa. HIV1 is divided into subtypes A-J and subtypes O and HIV2 into subtypes A-G. HIV infection in a country or a geographical region is usually caused by several prominent subtypes.

The transmission path of HIV1 and HIV2 is exactly the same.

Transmitted by sexual contact

The genital tract is one of the main routes by which the HIV virus is transmitted from an HIV-infected patient to a healthy person, infected cells and free viruses in vaginal fluids and semen are capable of transmitting the disease. The likelihood of transmission depends on many factors including the number of sexual contacts with an infected person, the presence of genital infections such as syphilis, gonorrhea, herpes infections, infections, and genital abrasions. sex...these factors increase HIV transmission

Transfusion through blood

Blood-borne viruses can be free, in lymphocytes, or in macrophages. This route of transmission is often caused by blood transfusion, or viral blood products, injections, tooth extraction, or occupational accidents caused by sharp objects such as knives, needles, test tubes contaminated with the patient's blood. . Superficial lesions on the skin may be the entry point for the virus when exposed to HIV-infected blood.

Passed from mother to child

HIV can be passed from mother to baby during pregnancy, during childbirth, and after birth. HIV is often passed on to the baby in the later stages of pregnancy. However, fetal transmission as early as 8 weeks after pregnancy was also investigated.

Laboratory diagnostics

The tests used to diagnose HIV are in principle not different from those of other viruses: Search for viruses or their antigens, then antibodies to the virus, viral nucleic acids can also be determined in laboratories. high-end experiment. HIV laboratory diagnosis is not an emergency test.

Antibodies to HIV components are detectable only about 6-8 weeks after HIV infection, so the diagnosis of HIV infection in the early stages is only by looking for viral antigens or nucleic acids. The following diagram shows the kinetics of HIV serological markers.

Image. Schematic representation of serological markers in the diagnosis of HIV

1. Identification of viral antigens.

Look for protein 24 (p24) by ELISA using a monoclonal antibody.

2. Virus isolation.

Inoculation of the patient's lymphocytes into a normal lymphocyte culture, the cytopathological effect appeared after 7-10 days of culture with the appearance of typical syncytial formation, however, some strains did not form syncytial cells when they were cultured. culture.

Identify antibodies

Multiple tests are used to detect HIV antibodies in patient serum. The following tests are widely used in laboratories to identify antibodies to the HIV virus

ELISA test

With a variety of techniques and antigens in which the antigen is mounted on the wall, the enzyme can be bound to an antibody (indirect ELISA technique), or an enzyme-bound antibody (competitive ELISA technique), or to an antibody. enzyme binding (sandwich ELISA technique). The sensitivity of this test ranges from 97.5 to 100%, when the ELISA test is positive a Western blot test is required to confirm the diagnosis.

Western blot test

This technique can identify antibodies to specific viral proteins, this is a valid test to confirm HIV infection, the result is positive when there are at least 2 protein bands of the envelope (gp 160, gp120, or gp 41) can add gag and pol gene cassettes or not, the reaction is negative when the above criteria are not met.

Determination of viral nucleic acids

PCR amplification test is used to determine the DNA or RNA of the virus in the patient's body, this technique also allows the quantification of the virus in the patient's blood.

Prevention and treatment

Prevent

Check donor blood treat blood before transfusion to rule out HIV. Medical instruments must be sterile, syringes, needles should only be used once.

It is necessary to advise staff who directly work with patients or with patient blood about safety rules, to avoid infection due to carelessness.

Prohibition of injection drug use and prostitution, education on safe sex There is currently no effective vaccine to prevent the disease.

Treatment

Research on antiretroviral drugs for HIV targets the steps in the viral development cycle: inhibition of the attachment and inclusion of the virus to the cell membrane, inhibition of nucleocapsid uncoating and entry into the cell, inhibition of nucleocapsid metabolism. reverse transcriptase, inhibition of viral cDNA binding to cellular chromosomes (provirus formation), inhibition of mRNA transcription, translation, inhibition of viral assembly, and viral replication out of the cell. Many probiotics such as antibodies and chemicals have been tested in the laboratory. Currently, two classes of drugs are available to treat HIV/AIDS infections:

Reverse transcriptase (RT) inhibitors such as azidothymidine, dideoxycytidine, didanosine, lamivudine...

Protease inhibitors such as saquinavir, ritonavir, indinavir...

The combination of these drugs reduces the amount of virus in the blood quickly, prolongs the patient's life, and limits drug-resistant viral strains