HIV infects cells by latching onto a specific receptor called CD4, which sits on the surface of certain immune cells. Once attached, the virus fuses with the cell membrane, injects its genetic material, and hijacks the cell’s own machinery to produce copies of itself. The entire cycle, from initial entry to the release of new viral particles, takes roughly 24 hours.
The Cells HIV Targets
HIV doesn’t attack just any cell. It specifically targets cells that carry the CD4 receptor on their surface. The primary victims are CD4+ T cells, a type of white blood cell that coordinates much of the immune response. HIV also infects cells from the immune system’s cleanup crew: monocytes, macrophages, and dendritic cells. A healthy adult has between 500 and 1,200 CD4 T cells per cubic millimeter of blood. As HIV destroys these cells over time, that count drops. A count below 200 is the clinical threshold for an AIDS diagnosis.
How the Virus Gets Inside
The outer shell of HIV is studded with clusters of two proteins, called gp120 and gp41, arranged in groups of three. These protein clusters act like keys. The infection process begins when gp120 makes contact with a CD4 receptor on the surface of a target cell. This initial binding changes the shape of gp120, exposing a hidden region that then reaches for a second receptor, called a coreceptor.
Two coreceptors can serve this role: CCR5 and CXCR4. Different strains of HIV prefer one or the other. Once gp120 locks onto both CD4 and a coreceptor, the second protein, gp41, springs into action. It punches into the cell’s membrane and pulls the virus and the cell together until their outer membranes merge. This opens a passage for the virus’s contents to spill into the cell.
A Genetic Shield Some People Carry
About 1% of people with European ancestry carry two copies of a mutation called CCR5-delta 32, a small deletion in the gene that builds the CCR5 coreceptor. Without a functional CCR5 on their cell surfaces, these individuals are nearly completely resistant to HIV infection, regardless of exposure. The mutation is most common in northern Europe, where 13 to 15% of people in Scotland and Scandinavia carry at least one copy. It drops to 4 to 6% in southern Europe and is essentially absent in populations from Africa and the Middle East.
Converting RNA to DNA
Once inside the cell, HIV faces an unusual problem. Its genetic blueprint is stored as RNA, but the host cell reads DNA. To solve this, the virus carries its own enzyme, called reverse transcriptase, that converts the single-stranded viral RNA into double-stranded DNA the cell can work with. This enzyme performs two jobs that it cannot do at the same time: it builds a new DNA strand using the RNA as a template, then it chews up the original RNA strand so a second DNA strand can be assembled. The whole conversion process takes about 8 to 12 hours.
Reverse transcriptase is notoriously sloppy. It makes frequent errors during copying, which is why HIV mutates so quickly and can develop resistance to drugs. This high error rate is also one reason a vaccine has been so difficult to develop: the virus is a constantly moving target.
Inserting Into Your DNA
The newly made viral DNA doesn’t just float around in the cell. It travels into the nucleus as part of a larger complex and gets permanently stitched into the cell’s own chromosomes. An enzyme the virus carries, called integrase, handles this insertion in two precise steps.
First, integrase trims two nucleotides off each end of the viral DNA, exposing reactive chemical groups. Then it cuts both strands of the host’s DNA, separated by exactly five base pairs, and joins the viral DNA ends to the host DNA at the cut sites. Cellular repair enzymes fill in the gaps, completing the splice. At this point, the viral DNA, now called a provirus, is a permanent part of the cell’s genome. Every time the cell divides, it copies the viral instructions right along with its own.
Making New Virus Particles
With its blueprint embedded in the host DNA, HIV waits for the cell to read those instructions. When the infected cell becomes activated, it transcribes the proviral DNA into messenger RNA, just as it would for any of its own genes. Some of that RNA becomes the genome for new viruses. The rest is translated into long chains of viral proteins.
The main structural protein, called Gag, is the workhorse of assembly. Roughly 2,500 copies of Gag gather at the inner surface of the cell membrane, drawn there by interactions with specific fats in the membrane. Each Gag protein grabs onto the viral RNA at one end and links up with neighboring Gag proteins along its middle, forming a curved lattice of hexagonal units. This lattice bends the cell membrane outward, creating a bulge. The virus also recruits host cell proteins that specialize in pinching off membrane buds. These cellular helpers finalize the separation, snipping the new particle free from the cell surface. Assembly of the protein shell takes about 10 minutes, and budding follows roughly 15 minutes after that.
Maturation Into an Infectious Particle
The freshly budded particle isn’t infectious yet. It’s an immature blob where the structural proteins are still connected in long, unprocessed chains. During or shortly after budding, a viral enzyme called protease cuts the Gag protein at five specific locations, separating it into its individual functional pieces. This cleavage triggers a dramatic internal rearrangement. The immature lattice falls apart, and the freed capsid proteins reassemble into the dense, cone-shaped core that characterizes a mature HIV particle. Only after this restructuring can the virus infect a new cell. Many antiretroviral drugs work by blocking protease, which leaves newly released particles stuck in their immature, non-infectious form.
How HIV Hides in the Body
Perhaps the most challenging aspect of HIV biology is its ability to go silent. When the virus integrates into the DNA of a CD4+ T cell that then returns to a resting state, the provirus sits dormant. The cell isn’t actively reading the viral genes, so no viral proteins appear on the cell surface. That makes the infected cell invisible to the immune system. These resting memory CD4+ T cells likely form when an actively infected cell survives both the virus’s destructive effects and the immune system’s attempts to kill it, then settles back into a quiet state carrying a permanent copy of HIV in its DNA.
HIV also exists in a second, less stable latent form: unintegrated viral DNA sitting in the cell’s cytoplasm, stalled before it could reach the nucleus. This form degrades over time, but the integrated form is remarkably durable. It can persist for years, even decades, despite effective antiretroviral therapy that suppresses the virus to undetectable levels in the blood. If treatment is interrupted, these silent reservoirs can reactivate and restart the infection. This latent reservoir is the central obstacle to curing HIV.