Pathogen and Genetic Variability
HIV is characterized by a striking rate of genetic mutation. During replication, the viral enzyme reverse transcriptase frequently makes errors, resulting in the generation of numerous related yet genetically distinct viral variants known as quasispecies. This allows the pathogen to effectively evade the host immune response and develop resistance to antiretroviral therapy.
The human immunodeficiency virus is divided into three main groups: M (main), N (new), and O (outlier). Group M, which is dominant worldwide, includes 10 subtypes. In Russia, HIV-1 group M, subtype A, is the predominant strain.
Tropism and Cellular Reservoirs
The pathogenesis of the infection is inextricably linked to specific cellular tropism. The classic pathway of entry involves the binding of the virus to the CD4 receptor. Such targets include T helper cells, monocytes, and macrophages. However, HIV is also capable of entering CD4-negative cells (astrocytes, intestinal and cervical epithelium, and capillary endothelium) by utilizing the chemokine coreceptors CCR5 and CXCR4.
Long-lived cells—macrophages and neuroglia—play a special role. Unlike T lymphocytes, they do not die rapidly. Virions accumulate within their cytoplasm and can persist for a long time as proviral DNA. These cells function as an invisible reservoir for the immune system. Meanwhile, dendritic cells perform a transport function by capturing the virus on mucous membranes and carrying it directly to the lymph nodes, where they infect new populations of T lymphocytes.
Mechanisms of T-Lymphocyte Death
The main cause of immunodeficiency in HIV is the depletion of the CD4+ T helper cell pool. Paradoxically, only about 1% of infected cells die from the direct cytopathic effect of the virus itself. The remaining 99% are destroyed indirectly (the "bystander" effect).
Main causes of massive immune cell death:
- Apoptosis: the virus triggers a self-destruction program in activated cells.
- Membrane fusion: the formation of multinucleated, non-viable syncytia.
- Antibody-dependent cellular cytotoxicity: viral proteins deposit on healthy cells, causing the host's own immune system to mistakenly destroy them as foreign.
The situation is compounded by the fact that the virus attacks stem cells, blocking the body's ability to replenish lost T lymphocytes.
Epidemiology and Virus Transmission
The source of infection is an infected individual at any stage of the disease, but maximum contagiousness is observed during the acute period and the AIDS stage, when the viral load in the blood reaches its peak. The infectious dose is approximately 10,000 virions.
Main routes of transmission:
- Sexual: The most frequent route (up to 86% of cases). The risk increases in the presence of STIs, mucosal microtraumas, and the absence of circumcision. Anal intercourse is the most hazardous due to the thinness of the rectal mucosa.
- Parenteral: Occurs via injections (especially among injection drug users), blood transfusions, or organ transplantation. The risk of infection from transfusing contaminated blood reaches 90–100%.
- Vertical: Transmission from mother to fetus in utero, during childbirth (60–85% of transmission cases), or during breastfeeding.
Briefly: answers to topical questions
What are the stages of the clinical course of HIV infection according to the Russian V.I. Pokrovsky classification?
According to the Russian V.I. Pokrovsky classification, there are five consecutive stages in the clinical course of HIV infection.
- Stage 1 — Incubation: from the moment of infection to the first immune system response.
- Stage 2 — Primary manifestations: the body's reaction to the introduction of the virus (includes asymptomatic, acute without secondary diseases, and acute with secondary diseases forms).
- Stage 3 — Subclinical: gradual progression of immunodeficiency with minimal manifestations.
- Stage 4 — Secondary diseases: development of opportunistic infections and malignancies (divided into substages 4A, 4B, 4C).
- Stage 5 — Terminal stage.
Which human biological fluids contain HIV in concentrations sufficient to cause infection?
The epidemiological hazard of biological fluids depends on the viral load. The greatest risk of infection is posed by:
- blood;
- semen and pre-ejaculatory fluid (pre-seminal fluid);
- vaginal and cervical secretions.
Sources also indicate that HIV is present in breast milk, and vertical transmission is possible during breastfeeding; meanwhile, breast milk, saliva, tears, and urine are classified as substrates with low/negligible virus concentrations. Saliva and tears are epidemiologically insignificant.
What is the resistance of HIV to physical and chemical environmental factors?
HIV is classified as a virus with low resistance to environmental factors.
- Temperature effect — the virus is thermolabile: it is inactivated by boiling for 1 minute, at 56°C for 30 minutes, but remains preserved for several years when frozen.
- Desiccation — it retains infectivity on surfaces for several hours, and in dried blood for several days.
- Chemical agents — rapid inactivation (within 1–5 minutes) is achieved using 70% and 96% ethanol, 0.5% sodium hypochlorite, 1% glutaraldehyde, and 6% hydrogen peroxide.
- Radiation — virions are sensitive to sunlight, artificial UV radiation, and ionizing radiation.
To remember the viral enzymes targeted by ART drugs, use the acronym PRI: Protease, Reverse transcriptase, Integrase.
Class and exam questions
Why is it impossible to completely eradicate HIV from the body?
The virus integrates into the genome of long-lived cells (e.g., macrophages) as proviral DNA. In this state, it is completely invisible to cellular immunity and can persist for years.
Can you get HIV from oral sex?
Yes, a risk exists, although it is significantly lower than with other types of sexual contact. Langerhans cells can act as primary targets for the virus on the oral mucosa.
Which blood products are safe regarding HIV?
Normal and specific immunoglobulins, as well as modern clotting factor concentrates, are safe because their manufacturing process involves rigorous thermal or chemical virus inactivation.
What else to study on this topic
- The Superantigen Effect of HIV and Polyclonal Lymphocyte Activation
- The Cytokine Paradox of Infected Macrophages (The "Decoy" Effect)
- Features of HIV Pathogenesis in Primate Animal Models
- The Role of Chemokine Receptors CCR5 and CXCR4 in Viral Entry
- Obstetric Risk Factors for Intrapartum Transmission
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