The Human Immunodeficiency Virus (HIV) is a retrovirus, meaning it carries its genetic information as RNA rather than DNA. This virus targets and disables the body’s immune system, ultimately leading to Acquired Immunodeficiency Syndrome (AIDS). Understanding the steps the virus takes to infect a cell is fundamental, as this mechanism is the basis for developing effective treatments. The process involves the virus hijacking the host cell’s machinery to replicate itself, dismantling the body’s ability to fight off infections.
Targeting and Cell Entry
The initial stage involves the virus attaching to its preferred host cell, primarily CD4+ T-lymphocytes, crucial components of the immune system. The HIV particle surface is studded with envelope glycoproteins, a complex of gp120 and gp41, which mediate this attachment. The gp120 subunit first binds to the CD4 receptor on the T-cell surface.
Binding to the CD4 receptor triggers a conformational change in the gp120 protein, exposing a binding site for a second molecule called a co-receptor. This co-receptor is typically either CCR5 or CXCR4, depending on the HIV strain. Subsequent binding causes a further structural change, forcing the gp41 subunit to insert a fusion peptide into the host cell membrane.
The gp41 protein then folds upon itself, effectively pulling the viral envelope and the cell membrane into close proximity. This action results in the fusion of the two membranes, creating a pore. The viral core, containing the genetic material and viral enzymes, is released into the cell’s cytoplasm, allowing the virus to transition to the next phase of replication.
Viral Conversion and Integration
Once the viral core is inside the host cell cytoplasm, the genetic code must be converted into a form the host cell can process. Since HIV’s genome is single-stranded RNA, it must be converted into double-stranded DNA. This conversion is performed by the unique viral enzyme carried within the core, known as reverse transcriptase.
Reverse transcriptase first uses the viral RNA as a template to synthesize a complementary DNA strand. It then removes the original RNA template and synthesizes a second, complementary DNA strand. This results in a complete double-stranded viral DNA molecule, called proviral DNA, which is then transported into the cell’s nucleus.
Inside the nucleus, a second viral enzyme, integrase, takes over the process. Integrase facilitates the splicing of the proviral DNA into the host cell’s chromosomal DNA. Integrase links the viral DNA into a specific region of the host genome. Once integrated, the viral DNA becomes a permanent part of the host cell’s genetic makeup, establishing a state of latency that can persist for the lifetime of the cell.
Replication, Assembly, and Release
The integrated proviral DNA acts as a blueprint, hijacking the cell’s machinery to produce new viral components. The host cell’s RNA polymerase begins transcribing the viral DNA into messenger RNA (mRNA) and full-length genomic RNA. The mRNA is then translated by the cell’s ribosomes to create long chains of viral proteins, specifically the Gag and Gag-Pol polyproteins.
These long polyprotein chains and genomic RNA molecules migrate to the inner surface of the host cell’s plasma membrane, which serves as the assembly platform. The Gag polyproteins drive the clustering and formation of an immature viral core, which pushes outward from the cell membrane. As this immature particle, or virion, buds away from the host cell, it acquires a lipid envelope studded with gp120/gp41 glycoproteins.
The final step, known as maturation, occurs after the virion has been released. The virion contains a third viral enzyme, protease, which activates and precisely cleaves the long Gag and Gag-Pol polyprotein chains into their smaller, functional components. This cleavage causes a structural rearrangement within the viral core, transforming the immature, non-infectious particle into a mature, infectious virion ready to infect another CD4+ T-cell.
The Immune System Impact
The continuous cycle of replication, assembly, and release has a devastating effect because the virus specifically targets and destroys CD4+ T-cells. These cells are central to coordinating the body’s adaptive immune response, signaling other cells to attack pathogens. The massive production of new virions either directly kills the infected CD4+ T-cells or triggers their programmed cell death, leading to a significant decline in their number.
The progressive depletion of CD4+ T-cells severely weakens the body’s defenses, leading to a state of immunodeficiency. A healthy adult typically has a CD4 count between 500 and 1500 cells per cubic millimeter of blood. When the CD4+ T-cell count drops below 200 cells per cubic millimeter, the condition is formally classified as Acquired Immunodeficiency Syndrome (AIDS).
This profound loss of immune function leaves the body susceptible to a variety of illnesses that a healthy immune system would normally suppress. These are known as opportunistic infections, which include fungal infections, severe bacterial infections, and specific cancers. It is these secondary infections and cancers, taking advantage of the damaged immune system, that ultimately cause severe illness and death in untreated individuals.