HIV infection and AIDS - Causes and pathogenesis

The causative agent of HIV infection

Two serotypes have been described - HIV-1 and HIV-2, differing in structural and antigen characteristics. In Ukraine, HIV-1 (the main causative agent of the disease) is of epidemiological significance.

Taxonomy of HIV

Human immunodeficiency virus belongs to the kingdom Viridae, family Retroviridae, subfamily Lentiviridae.

The main properties of the human immunodeficiency virus

The structure of the HIV viral particle

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

HIV-1 and HIV-2 protein groups

Protein groups	HIV-1	HIV-2
Envelope proteins (env)	GP160, GP120, GP41	Gр140, gр105, gр36
Core proteins (gag)	P17, p24, p55	P16, p25, p56
Viral enzymes (pol)	P31, p51, p66	R68

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

The center of the virion contains the viral genome, which consists of two RNA strands, internal proteins p7 and p9, and enzymes - reverse transcriptase (revertase), protease, RNase, and integrase (endonuclease). The genome is surrounded by an internal protein membrane. The HIV-1 internal membrane consists of proteins p17, p24, and p55. Proteins p16, p25, and p56 form the internal membrane of HIV-2. The outer lipid membrane of HIV-1 is penetrated by the glycoprotein gpl60, consisting of a transmembrane (gp41) and a highly immunogenic (gpl20) fragment. The membrane proteins gp41 and gpl20 are connected by a non-covalent bond and form processes on the surface of the virion that ensure the attachment of HIV to the receptors of human target cells.

Antigenic structure

The virus genome 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).

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Virus persistence in the environment

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

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

Heating to 56 °C for 30 minutes leads to 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 virions are treated with a 70% ethyl alcohol solution for a minute, they are inactivated. When exposed to 0.5% sodium hypochlorite, 1% glutaraldehyde, 6% hydrogen peroxide, 5% lysol, ether or acetone, the death of viral particles is also noted.

HIV is relatively insensitive to ultraviolet radiation and ionizing radiation.

Pathogenesis of HIV infection

Differentiation antigen CD4+ (CD - abbreviation for Cell Differentiation antigen) and non-specific (independent of the presence of CD4+) components are receptors for HIV. CD4+ is a glycoprotein with a molecular weight of 55,000 kDa. Its structure is similar to certain parts of immunoglobulins. The viral protein gpl20 has a similar structure - this determines the ability of virions to penetrate into the cell.

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

Types of cells affected by human immunodeficiency virus

Cell type	Tissues and organs
T-lymphocytes. macrophages	Blood
Langerhans cells	Leather
Follicular dendritic cells	Lymph nodes
Alveolar macrophages	Lungs
Epithelial cells	Large intestine, kidneys
Cervical cells	Cervix
Oligodendroglia cells	Brain

The HIV envelope contains proteins of the human histocompatibility complex of classes I and II, so the penetration of the virus into the body does not cause a rejection reaction. 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. Double-stranded RNA of the virus penetrates the cell, where with the help of reverse transcriptase, single-stranded proviral DNA is synthesized. Then, double-stranded DNA is formed, which is integrated into the cell DNA with the help of integrase. Viral DNA acts as a matrix for the synthesis of RNA, which assembles a new viral particle.

Genetic errors often occur during HIV replication, resulting in the formation of different subtypes of the virus.

After HIV penetrates CD4+ cells, its replication begins: the more active the CD4+ cells, the more intense the reproduction of the virus. Therefore, regulators that activate CD4+ cells provide increased replication of the virus. Such regulators include TNF: colony-stimulating factor (colony-stimulating factor), and IL-6.

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

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

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

At the initial stages of the disease, the body produces virus-neutralizing antibodies that suppress the activity of freely circulating viruses. However, such antibodies do not act on viruses that are in cells (proviruses). Over time (usually after 5-6 years), the immune system's protective capabilities are exhausted and, consequently, the virus accumulates in the blood.