Human Immunodeficiency Virus (HIV) is a lentivirus that, over time, causes Acquired Immunodeficiency Syndrome (AIDS), a condition where the immune system progressively fails, making the body susceptible to opportunistic infections and cancers. The HIV virion, a microscopic infectious particle, is responsible for this condition. This tiny entity, roughly 120 nanometers in diameter, is the vehicle by which HIV spreads and establishes infection, specifically targeting and damaging immune cells.
Components of the HIV Virion
The HIV virion has a structure, beginning with an outer lipid envelope derived from the host cell membrane during budding. Embedded within this envelope are viral glycoproteins, specifically gp120 and gp41, which appear as trimeric spikes. These glycoproteins are encoded by the viral env gene and attach to host cells.
Beneath the envelope lies the matrix protein p17, which surrounds the conical capsid. The capsid, composed of the p24 protein, encases the viral genetic material. Inside this capsid are two identical copies of single-stranded RNA, the virus’s genome.
Associated with the RNA are nucleocapsid proteins, p6 and p7, which protect the genetic material. The core also contains viral enzymes: reverse transcriptase, integrase, and protease. These enzymes are derived from the pol gene and are important for the virus’s replication cycle once it enters a host cell.
How the HIV Virion Enters Cells
The entry of the HIV virion into a host cell is a multi-step process. It begins with the binding of the gp120 glycoprotein on the virion’s surface to the CD4 receptor on target immune cells, such as CD4+ T-cells, macrophages, and dendritic cells.
This initial binding induces a conformational change in gp120, which then allows it to interact with a co-receptor, CCR5 or CXCR4. The interaction with the co-receptor further stabilizes the attachment and triggers another conformational change, this time in the gp41 transmembrane glycoprotein.
The gp41 protein undergoes rearrangement, inserting its fusion peptide into the host cell membrane. This pulls the viral and cellular membranes together, leading to their fusion. This fusion allows the viral core, containing the RNA genome and enzymes, to enter the host cell’s cytoplasm, initiating the infection.
Replication Inside the Host Cell
Once inside the host cell, the HIV virion begins replication. The viral capsid uncoats, releasing the single-stranded RNA genome and associated enzymes into the cytoplasm. The enzyme reverse transcriptase then transcribes the viral RNA into a complementary single-stranded DNA copy, and then a second DNA strand is synthesized, forming a double-stranded viral DNA.
The double-stranded viral DNA is then transported into the host cell’s nucleus. Here, the viral enzyme integrase facilitates the insertion of this viral DNA into the host cell’s chromosomal DNA, forming a provirus. Once integrated, the provirus can remain dormant or be activated.
When activated, the host cell’s machinery transcribes the proviral DNA into new viral RNA. Some RNA serves as the genome for new virions, while other copies are translated into viral proteins and polyproteins. The Gag and Gag-Pol polyproteins, along with new viral RNA, move to the cell surface for assembly.
Immature virions bud from the host cell’s plasma membrane, acquiring a lipid envelope containing viral glycoproteins. As the virion buds and matures, the viral protease enzyme cleaves the polyproteins into individual functional proteins, such as p17, p24, reverse transcriptase, integrase, and protease, leading to the formation of a fully infectious virion.
Factors Contributing to HIV’s Persistence
HIV’s persistence is linked to several characteristics of the virion and its life cycle. One factor is the virus’s high mutation rate, largely due to its error-prone reverse transcriptase enzyme. This enzyme introduces mutations, leading to diverse viral strains that evade the immune system and develop drug resistance.
Another factor is HIV’s ability to integrate its DNA into the host cell’s genome, forming a provirus. This integrated viral DNA can lie dormant in latency, creating viral reservoirs unaffected by antiretroviral therapies. These latent reservoirs can reactivate later, leading to renewed viral production even after prolonged treatment.
HIV specifically targets and destroys CD4+ T-cells, important immune cells. The progressive loss of these cells weakens the body’s ability to fight off infections and cancers, contributing to the development of AIDS and making eradication difficult.