Autophagy pathway intersects with HIV-1 biosynthesis and regulates viral yields in macrophages

George B. Kyei, Christina Dinkins, Alexander S. Davis, Esteban Roberts, Sudha B. Singh, Chunsheng Dong, Li Wu, Eiki Kominami, Takashi Ueno, Akitsugu Yamamoto, Maurizio Federico, Antonito Panganiban, Isabelle Vergne, Vojo Deretic

Research output: Contribution to journalArticlepeer-review

393 Scopus citations

Abstract

Autophagy is a cytoplasmic degradative pathway that can participate in biosynthetic processes, as in the yeast Cvt pathway, but is more commonly known for its functions in removing damaged or surplus organelles and macromolecular complexes. Here, we find that autophagy intersects with human immunodeficiency virus (HIV) biogenesis, mirroring the above dichotomy. Early, nondegradative stages of autophagy promoted HIV yields. HIV Gagderived proteins colocalized and interacted with the autophagy factor LC3, and autophagy promoted productive Gag processing. Nevertheless, when autophagy progressed through maturation stages, HIV was degraded. This, however, does not occur, as the HIV protein Nef acts as an antiautophagic maturation factor through interactions with the autophagy regulatory factor Beclin 1, thus protecting HIV from degradation. The dual interaction of HIV with the autophagy pathway enhances viral yields by using the early stages while inhibiting the late stages of autophagy. The role of Nef in the latter process enhances yields of infectious HIV and may be of significance for progression to clinical AIDS.

Original languageEnglish
Pages (from-to)255-268
Number of pages14
JournalJournal of Cell Biology
Volume186
Issue number2
DOIs
StatePublished - Jul 27 2009

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