Human Immunodeficiency Virus, or HIV, is a type of retrovirus that specifically targets the human immune system. Like all viruses, HIV cannot reproduce on its own; it must invade a host cell and hijack its internal machinery to create new copies of itself. Understanding this process, known as the viral life cycle, helps explain how HIV causes disease and how treatments work.
Targeting Specific Cells
HIV does not infect all cells indiscriminately; it primarily targets specific immune cells known as CD4+ T lymphocytes, or CD4 cells. These cells coordinate the immune system, signaling other immune cells to fight infections. The virus infects by attaching to proteins on the surface of CD4 cells.
Attachment involves two viral envelope proteins: glycoprotein 120 (gp120) and glycoprotein 41 (gp41). The gp120 protein on HIV binds to the CD4 receptor on the host T cell. This binding changes gp120, allowing it to then bind to a co-receptor (CCR5 or CXCR4) on the CD4 cell surface. This dual binding mechanism ensures the virus enters the correct target cells.
The Replication Cycle Steps
Binding and Fusion
After the gp120 protein binds to both the CD4 receptor and a co-receptor (CCR5 or CXCR4), a conformational change occurs in the gp41 protein. This change facilitates the fusion of the viral envelope with the host cell’s membrane. This fusion creates an opening, allowing the core contents of the HIV particle, including its genetic material and enzymes, to enter the cytoplasm of the host cell.
Reverse Transcription
Once inside the host cell, the viral single-stranded RNA genome is converted into double-stranded DNA. This transformation is performed by a viral enzyme called reverse transcriptase, which is carried within the HIV particle. This step is a defining characteristic of retroviruses, as they transcribe their genetic information “in reverse” from RNA to DNA, unlike most organisms that transcribe DNA to RNA. The newly synthesized viral DNA then becomes ready for transport.
Integration
The newly created double-stranded viral DNA, now referred to as a provirus, is then transported into the host cell’s nucleus. Inside the nucleus, another viral enzyme, integrase, facilitates the insertion of this proviral DNA into the host cell’s own chromosomal DNA. Once integrated, the provirus can remain dormant for long periods or become active, using the host cell’s machinery to produce new viral components. This integration makes the infection permanent, as the viral genetic material becomes a part of the host’s own genome.
Transcription and Translation
After integration, the host cell’s machinery is exploited to produce new viral components. The integrated proviral DNA is transcribed by the host cell’s RNA polymerase II into new viral RNA molecules. Some of these viral RNA molecules serve as the genetic material for new virus particles, while others are transported out of the nucleus to be translated into viral proteins. These proteins include enzymes required for replication, such as reverse transcriptase, integrase, and protease, as well as structural proteins that will form the new virus particles.
Assembly
The newly synthesized viral RNA genomes and viral proteins then migrate to the inner surface of the host cell’s membrane. At this location, they begin to assemble into new, immature HIV particles. The gag polyprotein, a precursor protein, plays a central role in this assembly process, forming the structural core of the nascent virus. This assembly process ensures that all necessary components are packaged efficiently into the new viral particle.
Budding and Maturation
After assembly, the immature HIV particles push through the host cell’s membrane, “budding off” and acquiring a piece of the host cell’s membrane as their outer envelope. At this stage, the particles are still non-infectious. The final step, maturation, occurs outside the host cell. The viral enzyme protease, which was packaged within the immature particle, becomes active and cleaves the long polyproteins into individual, functional viral proteins. This cleavage allows the core of the virus to condense and assume its mature, infectious shape, enabling it to infect new CD4+ T cells.
Impact of Replication on the Body
The continuous replication of HIV within the body has consequences for the immune system. Each cycle of replication leads to the destruction of infected CD4+ T cells, as the budding of new virus particles often damages the cell membrane beyond repair. Over time, this persistent destruction causes a progressive decline in the number of functional CD4+ T cells in the body.
As CD4+ cell counts fall, the immune system becomes increasingly compromised, making the body vulnerable. This weakening of the immune defenses eventually leads to Acquired Immunodeficiency Syndrome (AIDS), the most advanced stage of HIV infection. Individuals with AIDS are susceptible to opportunistic infections, which are illnesses caused by pathogens that normally do not cause disease in people with healthy immune systems, and certain types of cancers, due to the inability of their immune system to effectively fight them off.