HIV Might Hitch a Ride Into the Brain on Immune Cells, Researchers Find

By Steve Tokar HIV might find its way from the circulatory system into the brain and central nervous system (CNS) by hitching a ride on immune system cells without infecting those cells, according to a paper by researchers at the San Francisco VA Medical Center and the University of California, San Francisco. "HIV infection of the brain and CNS can lead to HIV dementia," says principal investigator Lynn Pulliam, MS, PhD, chief of microbiology at SFVAMC and professor of medicine and laboratory medicine at UCSF. "This is a previously unknown means by which the virus could get past the blood-brain barrier," the body's system for protecting the brain from harmful substances in the blood. The paper appears on April 16, 2008 in the online journal PLoS ONE, which is published by the Public Library of Science. According to lead author Hans Rempel, PhD, a research biologist at SFVAMC, the key to the process is a protein called sialoadhesin (Sn). The researchers discovered that in blood samples from patients infected with HIV, Sn levels are increased 12 to 15 times above normal on the surface of CD14 monocytes, which are immune cells that circulate in the blood. "Sn had previously been known as a marker of inflammation," Rempel notes. "We were the first to show that it is increased on circulating monocytes in the presence of HIV." Searching beyond the simple correlation between HIV infection and increased Sn, the researchers looked for "an actual interaction between HIV and Sn," says Rempel. They found that Sn on the monocyte's surface interacts with sialic acids on the virus's surface to bind HIV to the monocyte. In this way, the virus becomes attached to the monocyte without necessarily infecting it. "Since CD14 monocytes traffic in and out of the brain normally, right through the blood-brain barrier, it's possible that they could be bringing HIV into the brain with them," Pulliam speculates. Once in the brain, she says, the virus could then infect microglia, the brain's first-line immune cells, which are particularly susceptible to HIV infection. The process of an uninfected cell bringing infection with it is known as trans infection. Rempel cautions that while the model of HIV spreading to the brain by attaching to monocytes is "intriguing," it still needs to be demonstrated in people with HIV. "Do they really have virus attached to Sn? And can HIV migrate intact in this way across the blood-brain barrier and infect susceptible cells? We are working on those questions," he says. Pulliam says that if the model proves accurate, it will have important implications for HIV infected people who are on highly active antiretroviral therapy (HAART), the current standard treatment for HIV. "Sn expression on monocytes correlates with HIV viral load, even for those individuals on HAART," she notes. "So to minimize HIV infection of the CNS, it would be important to keep viral load as low as possible." Coauthors of the paper are Cyrus Calosing, BS, and Bing Sun, MD, PhD, of SFVAMC. The research was supported by grants from the National Institutes of Health and the California HIV/AIDS Research Program that were administered by the Northern California Institute for Research and Education.

"Sialoadhesin Expressed on IFN-Induced Monocytes Binds HIV-1 and Enhances Infectivity" Hans Rempel, Cyrus Calosing, Bing Sun, Lynn Pulliam PLOS One, April 2008 Full Text