Scientists have long suspected that HIV hijacks immune cells called dendritic cells to infiltrate the immune system. Now UCLA AIDS Institute researchers have shown that blocking HIV's access to a naturally occurring molecule on dendritic cells may cut their ability to smuggle the virus into other immune cells. Published in the May edition of the Journal of Virology, the discovery may lead to new drugs to prevent sexually transmitted HIV infection.
"Dendritic cells act like sentries to alert the immune system when a foreign agent tries to infiltrate the body," said Dr. Benhur Lee, UCLA assistant professor of microbiology, immunology and molecular genetics. "They also produce a molecule called DC-SIGN that plays a critical role in the sexual transmission of HIV. We wanted to see what would happen if we blocked how DC-SIGN functions in its natural environment."
Dendritic cells reside in the mucosal linings of the mouth, gut, genital and urinary tracts -- sites where sexually transmitted HIV often enters the body. By examining biopsies of human rectal tissues, the UCLA team was the first to study DC-SIGN on dendritic cells in their natural setting instead of a test tube.
Using a sugar-like compound that binds to DC-SIGN and a DC-SIGN-seeking antibody, the scientists were able to block HIV from binding to these dendritic cells.
"Our findings suggest that preventing HIV from binding to the dendritic cells may block their ability to carry HIV to other parts of the immune system," Lee said. "Our next step will be to investigate if this is true."
"We believe our findings point to a new therapeutic target for preventing HIV infection," said Dr. Peter Anton, UCLA professor of medicine. "Drugs could be developed to block the interaction between HIV and DC-SIGN, potentially reducing HIV's ability to spread infection at mucosal routes into the body."
The National Institute of Allergy and Infectious Diseases and the Rockefeller Brothers Fund supported the study. Lee and Anton's coauthors included Kevin Gurney, Julie Elliot, Ian McGowan, Hoorig Nassanian and Carol Song of UCLA, and Elizabeth Soilleux of Cambridge University.
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