Master of microevolution

The fight against HIV– a progress report

Bill Snyder
Published: April, 2004

Richard D’Aquila, M.D., director of the Vanderbilt-Meharry Center for AIDS Research, holds a vial of fluid from HIV-infected cultures in the Biohazard Level 3 lab at Vanderbilt University Medical Center.
Photo by Dean Dixon
It has only nine genes, encoding just 15 proteins. Yet HIV—the human immunodeficiency virus—is a master of microevolution. So far it has evaded every attempt to subdue it.

Combinations of drugs that block key viral enzymes can reduce the “viral load” in the bloodstream to near-undetectable levels, allowing patients to live healthier, more productive, and longer lives. Yet no medical intervention has been able to flush HIV from the body or—through a vaccine—prevent infection from occurring in the first place.

“It’s highly complex, even though it’s not a living organism,” says Richard D’Aquila, M.D., who directs a new federally funded AIDS Research Center operated jointly by Vanderbilt University Medical Center and Meharry Medical College in Nashville. “It lends new meaning to the word parasite.”

HIV is not “alive” in the sense that carries the instructions necessary to reproduce. Like other viruses, HIV must hijack the reproductive machinery of the cells it infects to make copies of itself. HIV is “sneakier” than many of its viral cousins, however. Through rapid adaptation to its changing environment, the virus rapidly mutates so that some of its progeny can escape the antibodies and anti-viral drugs that otherwise would neutralize it.

Another reason HIV is so hard to stop is that it attacks “helper” T lymphocytes, also called CD4 T cells, a type of white blood cell that “orchestrates” the body’s immune response to microbial invaders. CD4 refers to a cell surface receptor to which HIV binds.

Like generals barking out orders to their troops, helper T cells send out chemical signals that “activate” the two major arms of the immune system. In one arm, B cells produce antibodies that can neutralize free-floating microbes and thus prevent them from infecting cells. In the other, cytotoxic T cells secrete a variety of toxic substances to kill cells that have already been infected.

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