Target cells and mechanism of entry
For successful infection, the virus requires specific "ports of entry". The main marker of vulnerability is the CD4 receptor. The pool of cells expressing this receptor includes T-helper cells (Th lymphocytes), macrophages, follicular dendritic cells, cells of the islets of Langerhans, and brain microglial cells.
The process of pathogen entry into the cell is strictly sequential:
- Primary binding of the viral particle to the host cell CD4 receptor occurs.
- The virus interacts with chemokine coreceptors — CCR5 or CXCR4, which is an absolute prerequisite for subsequent fusion.
- Conformational (spatial) changes in the gp41 viral protein are triggered.
- Final fusion of the viral envelope and cell membrane occurs, after which the pathogen's genetic material enters the cytoplasm.
Viral life cycle
HIV replication is characterized by high speed and productivity. A complete cycle takes only 1–2 days, generating a colossal number of new viral particles—over one billion per cycle. The replication process itself can be divided into four key stages:
- Adsorption and entry. The virus attaches to receptors and enters via endocytosis.
- Integration. Viral RNA is released. Proviral DNA is synthesized on its template and then directly integrated into the genome of the infected host cell.
- Component synthesis. The cellular machinery starts working for the virus: viral RNA is synthesized, and necessary viral proteins are translated and formed.
- Viral exit. New viral particles undergo assembly, maturation, and leave the host cell by budding, ready to infect new targets.
Interaction with the immune system and reservoir formation
The pathogenesis of the disease is inextricably linked to the destructive effect of the virus on the immune system. A key factor is the cytopathic effect — interaction with HIV causes massive death of Th lymphocytes and neuroglial cells. This naturally leads to a sharp decrease in the absolute number of CD4 lymphocytes and an alteration of the normal CD4/CD8 ratio. In parallel, a humoral immune response is observed: B lymphocytes undergo nonspecific polyclonal activation.
However, not all infected cells die. Monocytes, macrophages, Langerhans cells, and dendritic cells are not destroyed (do not degrade) upon contact with the pathogen. They act as infection reservoirs, preserving the virus in the body for many years. The spread of infection from these reservoirs occurs via intercellular fusion, allowing the virus to effectively evade recognition and destruction by neutralizing antibodies.
Role of cells in viral dissemination (spread)
Different cell types play unique roles in the spread of the virus throughout the patient's body:
- Dendritic cells. They serve as the primary barrier and the first cells to encounter HIV during sexual transmission. Intraepithelial dendritic cells are localized in mucous membranes. In addition to classical CD4 and CCR5 receptors, they possess a lectin receptor. This receptor specifically binds to the gp120 viral protein, ensuring viral capture. Subsequently, dendritic cells transport the virus in infectious form directly to the lymph nodes, where they transmit it to Th lymphocytes via a specialized intercellular synapse.
- Macrophages. They act as a transport vehicle — a "Trojan horse". They transport the pathogen across the blood-brain barrier (BBB), ensuring infection penetrates brain tissue.
Overall outcome: progressive death of immune cells inevitably leads to severe immunodeficiency, clinically manifested by the onset of secondary opportunistic infections, malignancies, and various non-infectious pathologies.
Briefly: answers to topical questions
Which viral enzymes provide the synthesis of proviral DNA and its integration into the genome of the infected cell?
The synthesis of proviral DNA and its integration into the cell genome are provided by the viral enzymes reverse transcriptase and integrase.
- Reverse transcriptase (revertase, p66/p51) — performs reverse transcription, synthesizing double-stranded proviral DNA on a viral RNA template.
- Integrase (p31–32) — integrates the resulting viral cDNA into the host cell DNA to form a provirus.
Integration of the viral genome does not require division of the infected cell.
Which structural genes encode the main proteins of the HIV virion?
The main proteins of the HIV virion are encoded by three structural genes: gag, pol, and env.
- The gag gene — encodes structural proteins of the inner part of the virion (group-specific core antigens), including the major capsid protein p24, matrix protein p17, as well as proteins p9 and p7.
- The pol gene — encodes the viral enzyme complex localized inside the nucleocapsid (reverse transcriptase, integrase, protease, RNase).
- The env gene — encodes envelope proteins, which include the surface glycoprotein gp120 and the transmembrane glycoprotein gp41.
What changes in cellular and humoral immunity indicators are characteristic of the secondary immunodeficiency stage in HIV?
The progression of HIV infection and the development of secondary diseases are characterized by depletion of the immune system.
- Cellular immunity — as a result of interaction with HIV, Th lymphocytes (T-helpers) die, leading to a decrease in the number of CD4 lymphocytes and an altered CD4/CD8 ratio. Without ART, HIV progression is accompanied by a decrease in the percentage and absolute number of CD4+ cells.
- Humoral immunity — B lymphocytes undergo nonspecific polyclonal activation.
The absolute CD4+ count is a more reliable prognostic factor for HIV progression; the development of opportunistic infections depends on the actual number of circulating cells.
Which opportunistic infections are classified as AIDS-defining conditions?
AIDS-defining conditions and infectious lesions characteristic of the advanced AIDS stage include:
- Protozoal infections — toxoplasmosis.
- Viral infections — herpesvirus infection, hepatitis B and C.
- Bacterial/mycobacterial infections — tuberculosis, mycobacteriosis, salmonellosis.
- Fungal infections — cryptococcosis.
To remember the stages of the life cycle, use the acronym A-I-S-V: Adsorption, Integration, Synthesis, Exit. And the macrophage is easy to remember as a "Trojan horse" for the brain.
Class and exam questions
Why can antibodies not completely neutralize HIV?
The virus spreads from reservoir cells (macrophages, dendritic cells) via direct intercellular fusion. This mechanism allows it to transmit from cell to cell while avoiding release into the bloodstream and contact with neutralizing antibodies.
Which cells are the first to be infected during sexual transmission?
The virus is first encountered by intraepithelial dendritic cells of the mucous membranes. They capture virions using a lectin receptor (which binds to gp120) and carry them to the lymph nodes.
What is the role of macrophages in the pathogenesis of nervous system involvement?
Macrophages do not die upon infection, but instead act as a "Trojan horse". They are able to cross the blood-brain barrier, delivering the virus directly into brain tissue.
What else to study on this topic
- Conformational changes of the gp41 viral protein during membrane fusion
- Mechanism of viral transmission via intercellular synapse from dendritic cells to T-helper cells
- Alteration of the CD4/CD8 subpopulations ratio during infection progression
- Causes and consequences of nonspecific polyclonal activation of B lymphocytes
- Structure and functions of the dendritic cell lectin receptor
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