How HIV (Human Immunodeficiency Virus) Infects a Cell

HIV follows these steps as it infects cells and reproduces.

(1) Attachment of the virion to the receptor on the cell. In the case of HIV, its gp120 attaches to a T4 cell’s, or macrophage’s, CD4 receptor and the coreceptor CCR5 and/or CXCR4 = fusin. The following picture shows (artificially colored purple) virions on the surface of a (salmon colored) T cell.

(2) Fusion with the cell membrane. The following diagram illustrates this process. The receptors from the virions lock to those of the cell. Then the virus receptors pull back and force a contact with the cell membrane. The rest is history.

(3) Penetration of the cell membrane,

(4) Uncoating, whereby the virion sheds its coat and leaves the its envelope behind.

(5) Reverse transcription of ssRNA to ssDNA using the enzyme reverse transcriptase occurs within the capsid.

(6) DNA synthesis of a second strand to form dsDNA.

(7) Migration to the nucleus of the cell.

(8) Integration into the host nucleus using the enzyme integrase. The integrated DNA form of the virus is called a provirus.

(9) Viral transcription. Once within the host cell’s nucleus, HIV transfers its genetic code to that of the host and henceforth, the host cell can become a virus factory. The cell could lie dormant (non-replicating) for some time or it could immediately begin producing more viral RNA. Such dormant cells are usually T memory cells and are called resting cells.

(10) RNA nuclear transport moves the RNA out of the host nucleus toward the inner surface of the cell membrane.

(11) Protein synthesis, whereby long proteins are split into smaller pieces, using the enzyme protease.

(12) RNA packaging and virion reassembly using the split proteins.

(13) Reencapsidation.

(14) Viral proteins push against the cell membrane and begin budding.

 (15) Release of virions by either budding (see the pictures below, which were taken from a September 1998 issue of the New England Journal of Medicine) or cell lysis. The half-life of this processing of HIV into mature virions is about 90 minutes. Each infected cell can produce an average of 250 new virions by budding before it fails and dies.


HIV also has the capacity to release its gp120 once it attaches to a T cell. This fills that receptor site on the T cell and disables its immune function. Thus, even non-HIV-infected T cells can feel the negative effects of the virus.

The virus lodges in the follicular dendritic cells of the lymph system. In addition, the virus can hitch a ride on the dendritic-like cells present in the mucosa (in particular, the anal, vaginal, and oral mucosa), using a receptor designated DC-SIGN, without infecting the cell (van Kooyk, Figdor, et al. March 3, 2000 Cell). These cells also migrate to the lymph nodes. Once there, the virus attacks the T4 cells. After an extended period of fighting the virus, the body succumbs and the dendritic cells in the lymph nodes are “burned out.” For this reason, some people with advanced HIV disease do not produce antibody to the virus. The following picture shows T cells (roughly spherical) on dendritic cells.

he virus can persist indefinitely (or so it seems) as latent proviral DNA, capable of replicating at any time. There is a negative association between the activity level of cytotoxic T lymphocytes (CD8+) and viremia, the more active the T8 cells, the lower the reproduction rate of the virus. On the other hand, Saha, et al. published an article in the January 2001 issue of Nature Medicine showing that HIV can infect CD8+ cells without using either CD4 as a primary receptor nor either of the coreceptors CCR5 or CXCR4.

Research announced at the Twelfth International AIDS Conference in Geneva, Switzerland (6/98) showed that HIV can remain in resting (non-reproducing) T cells in so-called “latent reservoirs,” even after intensive drug therapy. Later work (5/99) estimated that the half-life of these latent reservoirs may be as long as forty to sixty years! Martin, et al. from NIH reported in January of 2001 that macrophages may also be latent reservoirs for HIV!


HIV does its dirty work by disabling the T4 helper cells, which are managers of the immune response. It can also directly affect the cytotoxic or killer-T cells. HIV suppresses the production of CD4+ T cells, infecting those cells and initiating apoptosis (one form of programmed cell death), and generally causing the cells to malfunction. The website for cellsalive (www.cellsalive.com) shows the process of apoptosis, wherein the cell begins to oscillate or bleb prior to lysing. Blebbing is an uncontrolled oscillation that eventually tears the cell apart.

Since macrophages have some CD4 receptors, they too are targets for HIV infection. Once infected, their lifespans seem to be extended indefinitely (they become immortal). This is especially problematic because macrophages can cross the blood-brain barrier. Hence, HIV has an avenue for attacking the brain, leading to AIDS dementia in a high proportion (55–65%) of those infected.

The B cells’ defense mechanisms do not work very well, because most of the virus is hidden away within the CD4 cells and is unavailable for attachment by antibody. Some good news is that antibody b12 does block gp120.

HIV affects B cells with CD21 by coaxing them to produce excessive amounts of nonessential antibodies. They then fail to respond to normal physiologic signals and are at increased risk of becoming cancerous.
In the December 15, 2000 issue of the Journal of Immunology, Marone and his colleagues at the University of Naples in Italy have discovered that the tat protein in HIV acts as a chemoattractant of monocytes and dendritic cells. Furthermore, basophils and mast cells exhibit CCR3 which HIV can use as a coreceptor, enhancing the production of tat and improving viral replicability.

HIV can also force the envelope glycoproteins to induce syncytia formation, whereby healthy T4 cells fuse to one another in a group surrounding an infected cell. This is a rather lethal form of the disease because it forces an abrupt drop in the CD4+ cell count and the resulting rise in the likelihood of opportunistic infections. The syncytia-inducing (SI) version of HIV seems to be most often found among intravenous drug users. At the December 1998 meeting of the American Society for Cell Biology, Soll, et al. reported that syncytia are much more common than previously thought. His group was even able to visualize a moving syncytium consisting of thousands of cells. These syncytia were short-lived, self-perpetuating masses that disrupted membranes made from collagen and punched holes in endothelial tissue. Unfortunately, collagen is a major constituent of lymph nodes and blood vessels are lined with endothelial tissue.

The journal AIDS 15:1627-1634 carried an article by P. Corbeau, et al. showing that as the CCR5 density on CD4+ cells increases so too does disease progression. Other work has shown that HIV can infect naive T cells which do not divide.

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