HIV infection requires B cells with special protein, University of Pittsburgh research...( lthy subjects and 20 adult patients wit...)

lthy subjects and 20 adult patients with HIV from the Multicenter AIDS Cohort Study (MACS), 10 of whom had suppressed virus due to antiretroviral therapy (ART) and 10 who had never undergone ART. Researchers found about 8 percent of these cells expressed DC-SIGN. The researchers also confirmed their presence in tissue by examining samples from five non-HIV tonsillectomy patients. In tonsils, a lymphoid organ where both T cells and B cells congregate and engage in cross talk, 26 percent of the B cells expressed DC-SIGN.

In one set of studies involving cells from the healthy subjects, the team activated DC-SIGN using two molecules that T cells typically engage in their communication with B cells. Once activated, the DC-SIGN B cells were placed in a culture with T cells and a small amount of virus. Within 24 hours, HIV had invaded the T cells while sparing the B cells. When researchers repeated the experiment without B cells, the HIV had little effect on the T cells alone. Pretreating the B cells with a molecule that blocks DC-SIGN activation before culturing them with both T cells and HIV was a deterrent against T cell infection as well, further proof that to invade T cells, HIV requires DC-SIGN expressed on B cells.

DC-SIGN was first identified as a dendritic cell-specific binding site for HIV, but with this study, Dr. Rinaldo and colleagues prove that B cells expressing DC-SIGN also are used by HIV to facilitate infection of T cells.

"As has been observed in DC-SIGN dendritic cells, we suspect the B cells internalize the virus and that the DC-SIGN serves as sort of a bridge HIV uses to reach the surface of T cells," noted Giovanna Rappocciolo, Ph.D., associate professor of infectious diseases and microbiology at GSPH and the study's first author.

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Contact: Lisa Rossi
rossil@upmc.edu
412-647-3555
University of Pittsburgh Medical Center
13-Jul-2006

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