Maturation of the HIV-1 core by a non-diffusional phase transition

Gabriel A. Frank, Kedar Narayan, Julian W. Bess, Gregory Q. Del Prete, Xiongwu Wu, Amy Moran, Lisa M. Hartnell, Lesley A. Earl, Jeffrey D. Lifson and Sriram Subramaniam ()
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Gabriel A. Frank: Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health
Kedar Narayan: Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health
Julian W. Bess: AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory
Gregory Q. Del Prete: AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory
Xiongwu Wu: Laboratory of Computational Biology, National Heart, Lung, and Blood Institute, National Institutes of Health
Amy Moran: National Laboratory of Medicine, National Institutes of Health
Lisa M. Hartnell: Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health
Lesley A. Earl: Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health
Jeffrey D. Lifson: AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory
Sriram Subramaniam: Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health

Nature Communications, 2015, vol. 6, issue 1, 1-9

Abstract: Abstract The formation of the HIV-1 core is the final step in the viral maturation pathway, resulting in the formation of infectious virus. Most current models for HIV-1 core formation suggest that, upon proteolytic cleavage from the immature Gag, capsid (CA) dissociates into the viral interior before reforming into the core. Here we present evidence for an alternate view of core formation by taking advantage of our serendipitous observation of large membrane-enclosed structures in HIV-1 supernatants from infected cells. Cryo-electron tomographic studies show that these structures, which contain ordered arrays of what is likely the membrane-associated matrix protein, contain multiple cores that can be captured at different stages of maturation. Our studies suggest that HIV maturation involves a non-diffusional phase transition in which the detaching layer of the cleaved CA lattice is gradually converted into a roll that ultimately forms the surface of the mature conical core.

Date: 2015
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DOI: 10.1038/ncomms6854

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