Study helps explain why HIV causes lifelong infection
The persistence of HIV infection despite antiretroviral treatment depends partly on which human genes the virus integrates, according to a new study by the University of Washington schools of Public Health and Medicine, Seattle Children’s Research Institute and the Fred Hutchinson Cancer Research Center.
Lead co-author Sherry McLaughlin, a senior scientist at Seattle Children’s, developed the test to analyze where HIV integrates into human chromosomes. The team analyzed 532 infected cells and sequenced the human chromosome where each virus was inserted, called the integration site. Specimens were analyzed from three individuals at three time points over approximately a dozen years of anti-HIV treatment.
The researchers discovered that when HIV inserts into cancer genes, the human cells proliferate more than when HIV is inserted into other genes. The proliferating cells form clones of infected cells. The novel insights into the mechanisms that allow HIV to persist should not only help design better therapies, but may also improve our understanding as to why effective HIV treatment does not lead to a normal life expectancy, said co-senior author Dr. Lisa Frenkel, UW adjunct professor of global health.
The retrovirus laboratory of co-senior author Dr. James Mullins, UW professor of microbiology, contributed to the study. The Mullins laboratory has designed sophisticated computational and molecular biology tools to examine the staying power and progression of HIV infections, as well as host/virus genetic interactions.
Frenkle, who is also UW professor of pediatrics and laboratory medicine, said the study was made possibel by a large team, including participants who volunteered to be studied for more than a decade.
The study appeared in the Aug. 1 issue of Science.
“The research brings us closer to understanding why HIV is such a long-lasting infection and may lead us to new avenues to cure HIV,” said co-lead author Dr. Thor A. Wagner, a UW assistant professor of pediatrics.