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Cell-associated HIV mucosal transmission: The neglected pathway

Dr. from (BUSM) and her colleagues are challenging dogma about the of the human immunodeficiency virus type 1 (HIV-1). Most research has focused on infection by free viral particles, while this group proposes that HIV is also transmitted by infected cells. While inside cells, HIV is protected from antibodies and other antiviral factors, and cell-to-cell virus occurs very efficiently through intercellular synapses. The Journal of Infectious Diseases (JID) has devoted their December supplement to this important and understudied topic.

The 10 articles, four from researchers at BUSM, present the case for cell-associated as an important element contributing to the HIV epidemic. Anderson chides fellow researchers for not using cell-associated HIV in their transmission models: “The failure of several recent vaccine and microbicide clinical trials to prevent may be due in part to this oversight.”

Approximately 75 million people in the world have been infected with HIV-1 since the epidemic started over 30 years ago, mostly through sexual contact and maternal-to-child transmission. A series of vaccine and microbicide clinical trials to prevent HIV transmission have been unsuccessful, and scientists are returning to the drawing board to devise new approaches. The JID supplement advocates for new strategies that target HIV-infected cells in mucosal secretions.

The publication presents evidence that HIV-infected cells populate genital secretions from HIV-infected men and women as well as breast milk, and genetic evidence suggesting that cell-associated HIV transmission occurs in people. Various models for studying cell-associated HIV transmission and molecular targets for intervention are also presented. Finally, the efficacy of current HIV prevention strategies against cell-associated HIV transmission and opportunities for further development are described.

Source

The collaborative team of BUSM researchers includes Drs. Deborah Anderson, Joseph Politch and Jai Marathe from the Departments of OB/GYN and Medicine, Manish Sagar from the Department of Medicine and Rahm Gummuluru from the Department of Microbiology. Collaborators include Drs. Roger LeGrand and Natalie DeJucq-Rainsford from France, Julie Overbaugh from the University of Washington, Tom Moench and Richard Cone from Johns Hopkins University, Kevin Whaley from Mapp Biopharmaceutical and Kenneth Mayer from Harvard Medical School. It is their hope that these articles will help to inform and invigorate the HIV prevention field and contribute to the development of more effective vaccine, treatment, and microbicide strategies for HIV prevention.

Funding was provided by the US National Institutes of Health (grant U19 AI096398) and the Fond de Dotation Pierre Berge, Sidation, France.

Boston University Medical Center