Pittsburgh, July 13 HIV infection of T cells requires activation of a molecule on the surface of B cells, a finding that reveals yet another pathway the virus uses in its insidious attack on the immune system, report University of Pittsburgh Graduate School of Public Health (GSPH) and School of Medicine researchers in PLoS Pathogens, an open-access journal published by the Public Library of Science. While preliminary, the research suggests a need for developing a class of antiviral drugs targeted against this molecule and offers an avenue that may prove critical for the prevention of HIV.
Nearly all approved HIV drug regimens and most of those being tested in clinical trials focus on T cells, where HIV replicates and thrives. HIV hijacks T cells by binding to a cell membrane molecule called CD4 and to either or both of two other receptors, from which the two strains of HIV, X4 and C5, take their names. Once anchored on the membrane, it's able to slither inside and take command of the cell. The new research identifies an important first step in a new pathway involving B cells that express a protein called DC-SIGN. While these cells themselves do not become infected, they play a pivotal role as an accomplice in HIV's takeover of T cells.
"We have new insight into how the virus does its damage. The pathway is surprisingly simple, yet it has important implications for future studies and drug development efforts that focus on reservoirs of HIV in cells other than T cells," said Charles R. Rinaldo, Jr., Ph.D., professor and chairman of the department of infectious diseases and microbiology at Pitt's GSPH and the study's senior author.
The researchers report evidence of DC-SIGN in subsets of B cells from both healthy subjects and HIV infected individuals. Laboratory studies of these cells indicate DC-SIGN is a point of entry for HIV and necessary for T cell infection.
B cells were isolated from blood samples obtained in 33 hea
'"/>
Contact: Lisa Rossi
rossil@upmc.edu
412-647-3555
University of Pittsburgh Medical Center
13-Jul-2006