HIV infection and AIDS: causes and pathogenesis

The causative agent of HIV infection

Two serotypes, HIV-1 and HIV-2, are described, differing in structural and antigenic characteristics. On the territory of Ukraine, HIV-1 (the main causative agent of the disease) has epidemiological significance.

Systematics of HIV

The human immunodeficiency virus is referred to the kingdom of Viridae, the family Retroviridae, the subfamily Lentiviridae.

The main properties of the human immunodeficiency virus

The structure of the viral particle of HIV infection

According to electron microscopy, the virus has a rounded shape and a complex structure. The diameter of the virion is 100-120 nm.

Groups of HIV-1 and HIV-2 proteins

Groups of proteins	HIV-1	HIV-2
Protein envelope virus (env)	Gp160, gp120, gp41	Gр140, gр105, gр36
Proteins of the core (gag)	P17, p24, p55	P16, p25, p56
Enzymes of the virus (pol)	P31, p51, p66	P68

Molecular weight of proteins is measured in kilodaltons (kDa): gp - glycoproteins; p - proteins.

In the center of the virion is the genome of the virus, represented by two strands of RNA, internal proteins of p7 and p9, as well as enzymes - reverse transcriptase (revertase), protease, RNase and integrase (endonuclease). The genome is surrounded by an internal protein membrane. The composition of the inner coat of HIV-1 includes proteins p17, p24 and p55. Proteins p16, p25 and p56 form the inner envelope of HIV-2. The outer lipid envelope of HIV-1 is penetrated by the glycoprotein gpl60. Consisting of a transmembrane (gp41) and a highly immunogenic (gpl20) fragment. The envelope proteins gp41 and gpl20 are connected by a non-covalent bond and form on the surface of the virion the processes providing the attachment of HIV to the receptors of human target cells.

Antigenic structure

The genome of the virus contains nine genes - three structural and six regulatory. The genome is a variable structure due to antigenic drift. There are a number of serological variants of the virus (for example, A, B, C, D, E, F, G, H).

[1], [2], [3], [4], [5], [6], [7], [8]

Stability of the virus in the environment

In vivo, HIV (in the dried state) remains active for several hours; in liquids containing a large number of viral particles, such as blood and ejaculate, for several days.

In frozen serum, the activity of the virus is determined for several years.

Heating to 56 ° C for 30 minutes results in a 100-fold decrease in the infectious titer of the virus. At a higher temperature (70-80 ° C), the virus dies after 10 minutes. When processing virions with 70% ethanol solution for a minute, their inactivation occurs. At the action of 0.5% sodium hypochlorite solution, 1% glutaraldehyde solution, 6% hydrogen peroxide solution, 5% lysol solution, ether or acetone also indicate the death of virus particles.

HIV is relatively insensitive to ultraviolet radiation and ionizing radiation.

Pathogenesis of HIV infection

The CD4 + differentiation antigen (CD is an abbreviation of Cell Differention antigen) and nonspecific (independent of the presence of CD4 +) components are receptors for HIV. CD4 + is a glycoprotein with a molecular weight of 55,000 kD. In its structure similar to certain areas of immunoglobulins. A similar structure has the protein of the virus gpl20 - this determines the ability of virion penetration into the cell.

The CD4 + receptor, located on the membrane of immunocompetent cells, performs the function of recognition of antigens (together with HLA proteins - the main class II histocompatibility complex).

Types of cells affected by the human immunodeficiency virus

Cell type	Fabrics and organs
T-lymphocytes. Macrophages	Blood
Cells of Langerhans	Leather
Follicular dendritic cells	The lymph nodes
Alveolar macrophages	Lungs
Epithelial cells	Large intestine, kidneys
Cervical cells	Cervix
Oligodendroglia cells	Brain

The envelope of HIV contains proteins of the human histocompatibility complex of classes I and II, therefore, the penetration of the virus into the body does not cause rejection reaction. The fixation of virions on the surface of the target cell occurs with the participation of the glycoprotein gpl20. The glycoprotein gp41 ensures the fusion of the viral envelope with the membrane of the target cell. The double-stranded RNA of the virus penetrates into the cell, where a single-stranded proviral DNA is synthesized using reverse transcriptase. Then, a double-stranded DNA is formed, which is embedded in the DNA of the cell using integrase. Viral DNA serves as a template for the synthesis of RNA, which collects a new viral particle.

Often, when replicating HIV, genetic errors occur. Thus, different virus subtypes are formed.

After the entry of HIV into the CD4 + cell, its replication begins: the more active the CD4 + cells, the more vigorous the reproduction of the virus. Therefore, regulators that activate CD4 + cells provide increased viral replication. Such regulators include TNF: a factor stimulating colony of granulocytes and macrophages (colony-stimulating factor), and IL-6.

Interferon and transforming growth factor are regulators that inhibit the replication of the virus. As studies have shown. TNF-a activates the transcription of proviral HIV-1 DNA in chronically infected T cells and macrophages. Monocytes synthesizing TNF-a. Not only induce the expression of HIV-infected cells, but also stimulate the activation of latent provirus. The simultaneous activity of TNF-a is recorded. IL-6 and a factor stimulating colonies of granulocytes and macrophages.

Immunopathogenetic signs of HIV infection - deficiency of T-link and B-link of the immune system: lack of complement and phagocyte components; decrease functions of nonspecific protection factors. Polyclonal activation of B-lymphocytes leads, on the one hand, to hypergammaglobulinemia, and on the other hand to a weakening of the ability of cells to produce virus neutralizing antibodies. There is an increase in the number of CECs and the formation of antibodies to lymphocytes; this causes an even greater decrease in the number of CD4 + -T-lymphocytes. They note the development of autoimmune processes. The defeat of the immune system in HIV infection is systemic.

Along with deficiency of CD4 + lymphocytes during the course of the disease, functional deficiency of CD8 + lymphocytes, NK cells (natural killers) and neutrophils increases. With the deterioration of the immune status, various infectious, allergic, autoimmune and lymphoproliferative diseases develop, as well as a syndrome inherent in the disease of immune complexes (these factors determine the clinical picture of HIV infection).

At the initial stages of the disease, viral neutralizing antibodies are produced in the body that suppress the activity of free-circulating viruses. However, such antibodies do not act on viruses located in cells (proviruses). Over time (usually after 5-6 years), the protective capacity of the immune system is depleted and, consequently, the accumulation of the virus in the blood.