Taxonomy and general characteristics
Human immunodeficiency virus belongs to the family Retroviridae, genus Lentivirus. Two types are distinguished — HIV-1 and HIV-2. HIV-1 is distributed worldwide and is the main causative agent of HIV infection, whereas HIV-2 occurs predominantly in West African countries. The genome is represented by RNA, which is characteristic of all retroviruses.
HIV is a complex virus: in addition to the nucleocapsid, it has an outer lipoprotein envelope (supercapsid) embedded with 72 glycoprotein spikes. Each spike consists of a transmembrane protein gp41 and a surface protein gp120. The capsid has a truncated cone shape.
Virion structure
Inside the capsid are:
- two identical plus-strand RNA molecules (such RNA allows for immediate translation);
- enzymes — reverse transcriptase, integrase, protease;
- nucleoproteins associated with RNA.
Externally, the capsid is surrounded by a matrix layer and a lipid envelope with glycoprotein spikes.
Genome: structural and functional genes
The structural genes include:
- gag — encodes matrix, capsid, and nucleocapsid proteins;
- env — encodes surface gp120 and transmembrane gp41;
- pol — encodes reverse transcriptase, integrase, and protease.
Among the functional (regulatory) genes, the key ones are:
- tat — enhances transcription of viral genes;
- nef — together with tat, decreases the expression of MHC class I, protecting the infected cell from cytotoxic T-lymphocytes;
- rev — controls the transport of viral mRNA from the nucleus to the cytoplasm;
- vif — inhibits the cellular enzyme APOBEC3G, which causes hypermutations in retroviral DNA.
Antigenic structure and enzymes
Key HIV antigens:
- gp41 — ensures fusion of the viral envelope with the host cell membrane;
- gp120 — binds to the CD4 receptor and coreceptor; bears the main antigenic determinant against which neutralizing antibodies are produced;
- p24 — capsid group-specific antigen, an important serological marker of infection (antibodies to it do not perform a protective function).
Enzyme functions: reverse transcriptase synthesizes DNA using viral RNA as a template; integrase inserts proviral DNA into the host cell genome; protease cleaves the precursor polypeptide into functional viral proteins.
Life cycle and target cells
- Adsorption: gp120 binds to the CD4 receptor and the chemokine coreceptor CCR5 or CXCR4.
- Fusion of the viral envelope with the cell membrane mediated by gp41.
- Penetration of the capsid into the cytoplasm, release of RNA.
- Reverse transcription: synthesis of viral DNA.
- Transport of DNA into the nucleus and integration into the host genome.
- Transcription of viral RNA, translation of the polyprotein, and its cleavage by protease.
- Virion assembly and budding.
Cells bearing CD4 and chemokine receptors are affected: T-helper cells, macrophages, follicular dendritic cells, Langerhans cells, and microglia. CD4-negative cells are also affected — astrocytes, cervical and intestinal epithelium, brain capillary endothelium, and cornea.
Epidemiology and clinical presentation
HIV infection is a typical anthroponosis. Routes of transmission: sexual (hetero- and homosexual without barrier protection), parenteral (blood transfusion, injection drug use, organ transplantation, occupational injuries), vertical (transplacental, during delivery, via breastfeeding).
Incubation period — from 3 weeks to 3 months. The stages are distinguished:
- Early acute — high viremia, mononucleosis-like syndrome, resolves with an increase in the number of CD8+ cytotoxic T cells.
- Latent — lasts for years, asymptomatic.
- Late (AIDS) — decline in CD4+ cells below 400/µL, development of opportunistic infections and tumors.
Evasion mechanisms and diagnostics
HIV evades the immune response through: integration of proviral DNA into the genome; high mutation rate of the env gene (variability of gp120/gp41); downregulation of MHC I expression by tat and nef proteins.
Laboratory diagnostics:
- ELISA confirmed by immunoblotting — detection of antibodies to gag and pol antigens;
- detection of the p24 antigen;
- immunological methods — counting CD4+ and CD8+ lymphocytes;
- PCR — assessment of viral load and therapy monitoring.
In the first weeks — the seronegative window period. After 1–2 weeks, p24 is detected, followed by seroconversion with the appearance of antibodies to gp120 and gp41. A drop in antibodies to p24 is a sign of transition to the AIDS stage. Protective immunity is not formed.
Treatment and Prevention
Antiretroviral therapy (ART) is used, including nucleoside and non-nucleoside reverse transcriptase inhibitors, protease inhibitors, integrase inhibitors, and fusion inhibitors. Concurrently, prevention and treatment of opportunistic infections are carried out. Pregnant women are prescribed a combination of two nucleoside inhibitors and a protease inhibitor; newborns are given zidovudine, which significantly reduces the risk of vertical transmission.
Prevention — social and anti-epidemic measures: condom use, safe needle handling, donor blood screening, individual hygiene items. Specific vaccine prophylaxis has not been developed to date.
Key points
- HIV is a complex RNA-containing retrovirus of the genus Lentivirus, possessing gp120 and gp41 within its spikes.
- Structural genes: gag, env, pol; regulatory genes: tat, rev, nef, vif.
- Viral enzymes: reverse transcriptase, integrase, protease — the main targets of ART.
- Adsorption requires the CD4 receptor and CCR5 or CXCR4 coreceptors.
- T-helper cells, macrophages, dendritic cells, microglia, and a number of CD4-negative cells are affected.
- The AIDS stage is diagnosed when CD4+ drops below 400/µL and opportunistic infections develop.
- Diagnostics is based on ELISA, immunoblotting, p24 detection, and PCR.
- Protective immunity is not formed; a vaccine has not been developed; the basis of prevention is barrier and anti-epidemic measures.