Noninfectious pathway for HIV found by HSPH team

HIV is a crafty virus. It attacks the body by invading and taking over the very cells meant to protect humans from infection. Hiding within cells such as macrophages and lymphocytes, the virus uses the body’s natural machinery to replicate itself, destroying the immune system and leaving patients open to a range of debilitating and deadly opportunistic infections.

Now, a team led by Harvard School of Public Health (HSPH) researchers has described a previously unappreciated pathway used by HIV to enter macrophages and has shown that the virus, once in the cells through this entryway, doesn’t appear to replicate. Rather than causing infection, the virus is destroyed, and an immune response may be triggered.

Macrophages are the immune system equivalent to a voracious eater, wandering the body in search of pathogens or worn-out cells. They engulf and digest intruders and unwanted cells and debris. Macrophages also regulate key aspects of immunity and inflammation.

The HSPH researchers suggest that these findings not only provide a better understanding of how HIV interacts with human cells, but also offer new considerations for HIV vaccine design. Their paper appeared online in the early edition of the Proceedings of the National Academy of Sciences on March 14 at http://www.pnas.org/cgi/content/abstract/0611263104v1 and was published in the March 20 issue of the printed journal.

The paper’s lead author is J. Roberto Trujillo, a former HSPH investigator of neurovirology and cell biology, who now works as the head of the laboratory of neurovirology at the Institute of Human Virology, University of Maryland. He conducted the research for the paper while at HSPH. His co-authors are Joseph Brain, Max Essex, Rick Rogers, Ramon Molina, and Mary Frances McLane, all of HSPH, and Fernando Dangond of Brigham and Women’s Hospital.

“This paper represents a highly productive interaction between HSPH scientists interested in virology and those focused on macrophage biology,” said Brain, senior author and Cecil K. and Philip Drinker Professor of Environmental Physiology in the HSPH Department of Environmental Health. “We have shown that a primitive, nonspecific receptor is relevant to host defenses against the HIV virus.”

— HSPH Communications