HIV, the virus that causes AIDS, has the ability to integrate into the human genome, making it extremely difficult to cure the infection. A new study by scientists at Seattle Children's Research Institute, University of Washington and Fred Hutchinson Cancer Research Center found that when HIV integrates into genes involved with cancer, these cells tend to reproduce to a greater extent than others HIV-infected cells. The study was published on July 10, 2014 in the online edition of the journal Science.
"Our findings suggest that HIV may modify the function of some infected cells and that increased proliferation of these cells allows them to survive despite effective treatment," said Thor A. Wagner, M.D., of the Center for Global Infectious Disease Research at Seattle Children's Research Institute and co-lead author of the study. Wagner is also assistant professor of pediatrics at the University of Washington.
"Using a test we developed to analyze both the HIV sequence and where it integrates into the chromosome, we found that when HIV inserts into cancer genes the cells containing the virus proliferate more than other HIV-infected cells," said Sherry McLaughlin, Ph.D., senior scientist in the Center for Global Infectious Disease Research at Seattle Children's Research Institute, research scientist in microbiology at the University of Washington, and co-lead author of the study. "This proliferation may maintain the virus in the body, so that if treatment is stopped, the virus can again become active." Since 1995 patients living with HIV have been able to stop the disease from progressing by taking a combination of three antiviral drugs to suppress replication of the virus to undetectable levels. In 1996, measurements of the decline of the virus-infected cells in people taking the medications predicted that complete suppression of the virus for three years would cure the infection. More recently it has become clear that despite effective treatment HIV-infected cells decline much more slowly. This new research suggests that the infection persists in part because the virus is integrated into certain human genes that favor survival.
According to Dr. Wagner, "This research brings us closer to understanding why HIV is such a long lasting infection and may lead us to new avenues to cure HIV." For the multi-year study, a total of 534 proviral integration sites were sequenced from three participants at three time-points each. HIV integration at the same chromosomal site was found in multiple cells within each participant throughout follow up, whereas no identical integration sites were shared by different participants, suggesting that HIV-infected cells proliferate.
Three approaches were used to explore whether the distribution of HIV integration sites observed was random or shaped by selective forces. Specifically, researchers examined the distribution of HIV integrations and found them to be in genes associated with cancer, regulation of cell proliferation, or cell survival more than expected.
- T. A. Wagner, S. McLaughlin, K. Garg, C. Y. K. Cheung, B. B. Larsen, S. Styrchak, H. C. Huang, P. T. Edlefsen, J. I. Mullins, L. M. Frenkel. Proliferation of cells with HIV integrated into cancer genes contributes to persistent infection. Science, 2014; DOI: 10.1126/science.1256304
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