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

¹ Department of Molecular Genetics and Microbiology and ² Department of Cell Biology and Physiology, University of New Mexico School of Medicine, Albuquerque, NM 87131
³ Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, WI 53226
⁴ Department of Biochemistry, Juntendo University School of Medicine, Tokyo 113-8421, Japan
⁵ Nagahama Institute of Bio-Science and Technology, Tamura 1266, Nagahama, Shiga 526-0829, Japan
⁶ National AIDS Center, Istituto Superiore di Sanita, 00161 Rome, Italy

Correspondence to Vojo Deretic: vderetic{at}salud.unm.edu

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 Gag-derived 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.

Abbreviations used in this paper: 3MA, 3-methyl adenine; AIDS, acquired immune deficiency syndrome; ANOVA, analysis of variance; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; HIV, human immunodeficiency virus; MDM, monocyte-derived macrophages; MVB, multivesicular body; PI3K, phosphatidylinositol 3-kinase; Tor, target of rapamycin; VLP, virus-like particle; VSV-G, vesicular stomatitis virus G.

© 2009 Kyei et al.
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).

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This article has been cited by other articles:

• Leib, D. A., Alexander, D. E., Cox, D., Yin, J., Ferguson, T. A. (2009). Interaction of ICP34.5 with Beclin 1 Modulates Herpes Simplex Virus Type 1 Pathogenesis through Control of CD4+ T-Cell Responses. J. Virol. 83: 12164-12171 [Abstract] [Full Text]  
• Kyei, G. B., Dinkins, C., Davis, A. S., Roberts, E., Singh, S. B., Dong, C., Wu, L., Kominami, E., Ueno, T., Yamamoto, A., Federico, M., Panganiban, A., Vergne, I., Deretic, V. (2009). Autophagy pathway intersects with HIV-1 biosynthesis and regulates viral yields in macrophages. JEM 206: i16-i16 [Full Text]  
• LeBrasseur, N. (2009). HIV uses autophagy for its own means. JCB 186: 165-165 [Full Text]  

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