VACCINES AND ANTI-INFECTIVES : How HIV Invades Us - Brief Article

Applied Genetics News, March, 2000

Dutch and American research teams may have discovered how the human immunodeficiency virus (HIV) first enters the body through mucosal surfaces such as the rectum, cervix, and uterus. The findings suggest that HIV enters the body by attaching itself to dendritic cells on mucosal surfaces. After infecting these cells, HIV then hitches a ride into the lymphoid tissues, where the virus proceeds to infect the rest of the immune system. Their findings are reported in the March issue of Cell.

Dendritic cells are normally the watchdogs of the immune system, patrolling skin and mucosal surfaces. When dendritic cells see a foreign invader, such as a microorganism, they capture it, shred it and display pieces of proteins from the invading pathogen on their surfaces. These displayed proteins serve to alert other immune system cells, such as T-cells, that the body is under attack.

In the Cell paper, the researchers identify a specific dendritic cell receptor, called DC-SIGN, to which HIV attaches. Antibodies against DC-SIGN inhibited HIV infection in mixtures of dendritic and T-cells. DC-SIGN is identical to a glycoprotein from human placental tissue that researchers at Bristol-Myers Squibb had previously identified as a receptor of the HIV envelope protein gp120.

Studies in Howard Hughes investigator Dan Littman's laboratory at New York University by Teunis Geijtenbeek and Douglas Kwon revealed that the virus did, indeed, attach to dendritic cells via DC-SIGN, but that it did not subsequently infect these cells. Instead, the virus uses the dendritic cell as a Trojan horse to invade lymphatic tissue and infect T-cells.

"If these findings are validated in vivo, DC-SIGN could become a key target for trying to block at least the early stages of HIV infection," says Littman. Since the key components of gp120 that bind to DC-SIGN are likely to be conserved across many strains of HIV, vaccines that elicit antibodies that prevent the union of gp120/DC-SIGN could prove widely effective.

The researchers also plan to explore how HIV avoids degradation when it attaches to dendritic cells. "The virus might somehow disable the dendritic cell's destructive mechanism, creating for itself a sort of 'stealth weapon' by which it can enter the body," comments Littman.