Anthony Fauci, MD, a scientist at the forefront in the war against AIDS since the start of the epidemic a quarter century ago, presented at the William J. Rutter Center at UCSF Mission Bay an overview of and update on the latest battles last Friday. Fauci, director of the National Institute of Allergy and Infectious Diseases, described what researchers have recently learned about HIV infection, epidemiological trends, and prevention and treatment strategies.
The occasion was the annual Merle Sande Memorial Lecture, sponsored by the UCSF-affiliated Gladstone Institute of Virology and Immunology. Fauci reminded the audience that HIV remains a major challenge in the United States and around the world.
Antiretroviral drug cocktails are lifesavers, but for every person infected with HIV who is newly treated with antiretrovirals, another three to four are infected with the virus, Fauci said. He noted a recent 13 percent increase in HIV cases among men who have sex with men. In Washington, DC, one in 20 residents is infected with HIV, a rate comparable to parts of Africa. Nor are other highly developed countries immune from this trend. Thirteen western European countries recently experienced an increase in HIV infection rates.
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The virus has a long-known capability to embed its genetic blueprint within infected, but dormant "memory" T cells of the immune system. Those are the cells primed to respond quickly to the reappearance of an infectious agent that the immune system has seen before. HIV infection may persist in latent form within these long-lived, dormant cells - but with the potential to flare up again. Antiretroviral treatments are unable to vanquish this latent HIV.
Fauci noted advances in understanding the biology of how cells keep HIV latent, as well as the discovery of more than 200 proteins from the cells of its human host that HIV uses to go through its replicative life cycle. As it stands, the goal of eradicating the virus within its human host appears insurmountable, Fauci said.
Fauci concluded that medicine requires a much better set of tools to help prevent the spread of HIV infection. He noted scientific research that now has shown that circumcision helps prevent HIV transmission. But he also noted the failure of a Merck vaccine and of new antimicrobial treatments.
Toward the end of his talk, Fauci described how HIV invades the gut and drastically depletes memory CD4 T cells of the immune system within the tissue there.
On Sunday, Fauci's most recent study on HIV's attack on the immune system in the gut was published online in the journal Nature Immunology. Fauci's research team described how HIV is able to quickly disseminate to lymph tissue associated with the gut soon after infection begins. The virus then replicates prolifically within memory CD4 T cells in the lymph tissue.
The outer envelope protein of HIV attaches to an activated form of a protein known as integrin alpha-4 beta-7, which is associated with memory CD4 cells in the gut, but rarely with memory CD4 cells in other tissues. The attachment paves the way for the virus to spread from cell to cell.
According to Warner C. Greene, MD, PhD, director of the Gladstone Institute of Virology and Immunology, "These findings are an important advance as they begin to decipher why HIV so quickly and effectively attacks memory CD4 T cells residing in the gut-associated lymphoid tissue."
The Merle Sande Memorial Lecture was established to honor Merle A. Sande, MD, former chief of medicine at San Francisco General Hospital (SFGH) and vice chair of the Department of Medicine at the University of California, San Francisco. At SFGH, Sande created the first inpatient hospital unit in the world dedicated to the care of patients with AIDS, and was instrumental in developing infection control standards for the disease.
HIV-1 Envelope Protein Binds to and Signals Through
Integrin 47 the Gut Mucosal
Homing Receptor for Peripheral T Cells
James Arthos, Claudia Cicala, Elena Martinelli, Katilyn Macleod, Donald Van Ryk, Danlan Wei, Zhen Xiao, Timothy D Veenstra, Thomas P Conrad, Richard A Lempicki, Sherry McLaughlin, Massimiliano Pascuccio, Ravindra Gopaul, Jonathan McNally, Catherine C Cruz, Nina Censoplano, Eva Chung, Kristin N Reitano, Shyam Kottilil, Diana J Goode, Anthony S Fauci
Nature Immunology, Published online Feb. 10, 2008
Abstract | Full Text | Full Text (PDF)