Target Cells and Mechanism of Entry
For successful infection, the virus requires specific "entry portals." The primary marker of vulnerability is the CD4 receptor. The pool of cells expressing this receptor includes T-helper cells (Th-lymphocytes), macrophages, follicular dendritic cells, Langerhans cell islets, and brain microglia.
The process of pathogen entry into the cell is strictly sequential:
- Primary binding of the viral particle to the host cell's 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 viral protein gp41 are triggered.
- Final fusion of the viral envelope and cell membrane occurs, after which the genetic material of the pathogen enters the cytoplasm.
Viral Life Cycle
HIV replication is characterized by high speed and productivity. A full 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 integrated directly into the infected host cell's genome.
- Component Synthesis. The cellular machinery is hijacked to work for the virus: viral RNA synthesis, translation, and formation of necessary viral proteins occur.
- Viral Egress. New viral particles are assembled, mature, and leave the host cell via 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 impact of the virus on the immune system. A key factor is cytopathic effect — through interaction with HIV, Th-lymphocytes and neuroglial cells undergo massive apoptosis and destruction. This logically leads to a sharp decline in the absolute count of CD4 lymphocytes and an altered normal CD4/CD8 ratio. Concurrently, a humoral immune response is observed: B-lymphocytes undergo non-specific polyclonal activation.
However, not all infected cells perish. Monocytes, macrophages, Langerhans cells, and dendritic cells are not destroyed (do not degrade) upon contact with the pathogen. They function as infection reservoirs, preserving the virus in the body for years. Dissemination of infection from these reservoirs occurs via intercellular fusion mechanisms, allowing the virus to effectively evade recognition and destruction by neutralizing antibodies.
Role of Cells in Viral Dissemination
Different cell types play unique roles in spreading the virus throughout the patient's body:
- Dendritic Cells. These 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 viral protein gp120, ensuring viral capture. Subsequently, dendritic cells transport the virus in infectious form directly to lymph nodes, where they transfer it to Th-lymphocytes via a specialized intercellular synapse.
- Macrophages. They act as a transport vehicle — a "Trojan horse." Specifically, they carry the pathogen across the blood-brain barrier (BBB), ensuring infection penetrates brain tissue.
Overall Outcome: The progressive depletion of immune cells inevitably leads to severe immunodeficiency, clinically manifested by secondary opportunistic infections, malignancies, and various non-infectious pathologies.