A Yale-led team has discovered yet another molecular trick HIV uses to survive immune system attacks, a finding that may influence efforts to develop an effective vaccine against HIV/AIDS.
The virus forms specifically shaped structures called trimers on its surface, which are designed to attach to and infect cells and produce more HIV. To escape the immune system, the trimer can change shapes over time into three separate conformations. Vaccines now under development target one form of those structures in order to spur an immune system response. However, the new study published April 10 in the journal Nature shows that the HIV may escape immune system detection by hiding in yet another trimer conformation, called State 1.
Patients fight HIV by developing broadly neutralizing antibodies, and most of these antibodies recognize the State 1 conformation, the authors report.
“If these antibodies can bind to a trimer in State 1, any immunogens in a vaccine should recognize this conformation,” said Walther Mothes, professor of microbial pathogenesis and co-senior author of the paper. “Surprisingly, however, current immunogens recognize the State 2 conformation and apparently elicit State 2-specific antibodies.”
Mothes’ lab plans to help determine the State 1’s structure, which could potentially lead to immunogens that recognize this conformation.
Yale’s Maolin Lu is lead author of the paper. Scott C. Blanchard of Weill Cornell Medicine and Joseph G. Sodroski of Harvard Medical School are co-senior authors.
Mothes is also leader of Yale Cancer Center’s Virus and Other Infection-associated Cancers Research Program.
Reference: “Associating HIV-1 envelope glycoprotein structures with states on the virus observed by smFRET” by Maolin Lu, Xiaochu Ma, Luis R. Castillo-Menendez, Jason Gorman, Nirmin Alsahafi, Utz Ermel, Daniel S. Terry, Michael Chambers, Dongjun Peng, Baoshan Zhang, Tongqing Zhou, Nick Reichard, Kevin Wang, Jonathan R. Grover, Brennan P. Carman, Matthew R. Gardner, Ivana Nikić-Spiegel, Akihiro Sugawara, James Arthos, Edward A. Lemke, Amos B. Smith III, Michael Farzan, Cameron Abrams, James B. Munro, Adrian B. McDermott, Andrés Finzi, Peter D. Kwong, Scott C. Blanchard, Joseph G. Sodroski and Walther Mothes, 10 April 2019, Nature.