Assembly and budding

Assembly and budding

Newly made HIV core proteins, enzymes, and genomic RNA gather inside the cell and an immature viral particle forms and buds off from the cell, acquiring an envelope that includes both cellular and HIV proteins from the cell membrane. During this part of the viral life cycle, the core of the virus is immature and the virus is not yet infectious. The long chains of proteins and enzymes that make up the immature viral core are now cut into smaller pieces by a viral enzyme called protease.

This step results in infectious viral particles. Drugs called protease inhibitors interfere with this step of the viral life cycle. FDA has approved eight such drugs--saquinavir, ritonavir, indinavir, amprenavir, nelfinavir, fosamprenavir, atazanavir, and lopinavir--for marketing in the United States. An HIV inhibitor that targets a unique step in the viral life cycle, very late in the process of viral maturation, has been identified and is currently undergoing further development.

Recently, researchers have discovered that virus budding from the host cell is much more complex than previously thought. Binding between the HIV Gag protein and molecules in the cell directs the accumulation of HIV components in special intracellular sacks, called multivesicular bodies (MVB), that normally function to carry proteins out of the cell. In this way, HIV actively hitch-hikes out of the cell in the MVB by hijacking normal cell machinery and mechanisms. Discovery of this budding pathway has revealed several potential points for intervening in the viral replication cycle.

Transmission of HIV

Among adults, HIV is spread most commonly during sexual intercourse with an infected partner. During intercourse, the virus can enter the body through the mucosal linings of the vagina, vulva, penis, or rectum or, rarely, via the mouth and possibly the upper gastrointestinal tract after oral sex. The likelihood of transmission is increased by factors that may damage these linings, especially other sexually transmitted infections that cause ulcers or inflammation.

Research suggests that immune system cells of the dendritic cell type, which live in the mucosa, may begin the infection process after sexual exposure by binding to and carrying the virus from the site of infection to the lymph nodes where other immune system cells become infected. A molecule on the surface of dendritic cells, DC-SIGN, may be critical for this transmission process.

HIV also can be transmitted by contact with infected blood, most often by the sharing of needles or syringes contaminated with minute quantities of blood containing the virus. The risk of acquiring HIV from blood transfusions is extremely small in the United States, as all blood products in this country are screened routinely for evidence of the virus.

Almost all HIV-infected children in the United States get the virus from their mothers before or during birth. In the United States, approximately 25 percent of pregnant HIV-infected women not receiving antiretroviral therapy have passed on the virus to their babies. In 1994, researchers showed that a specific regimen of the drug AZT (zidovudine) can reduce the risk of transmission of HIV from mother to baby by two-thirds. The use of combinations of antiretroviral drugs and simpler drug regimens has further reduced the rate of mother-to-child HIV transmission in the United States.

In developing countries, cheap and simple antiviral drug regimens have been proven to significantly reduce mother-to-child transmission at birth in resource-poor settings. Unfortunately, the virus also may be transmitted from an HIV-infected mother to her infant via breastfeeding. Moreover, due to the use of medicines to prevent transmission at delivery, breastfeeding may become the most common mode of HIV infection in infants. Thus, development of affordable alternatives to breastfeeding is greatly needed.