Kyei George B, Dinkins Christina, Davis Alexander S, Roberts Esteban, Singh Sudha B, Dong Chunsheng, Wu Li, Kominami Eiki, Ueno Takashi, Yamamoto Akitsugu, Federico Maurizio, Panganiban Antonito, Vergne Isabelle, Deretic Vojo
Department of Molecular Genetics and Microbiology, University of New Mexico School of Medicine, Albuquerque, NM 87131, USA.
J Cell Biol. 2009 Jul 27;186(2):255-68. doi: 10.1083/jcb.200903070.
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.
自噬是一种细胞质降解途径，它可以参与生物合成过程，如酵母中的Cvt途径，但更因其在清除受损或多余细胞器及大分子复合物方面的功能而为人所知。在此，我们发现自噬与人类免疫缺陷病毒（HIV）的生物发生相互交叉，这反映了上述二分法。自噬的早期非降解阶段促进了HIV的产生。HIV Gag衍生蛋白与自噬因子LC3共定位并相互作用，且自噬促进了Gag的有效加工。然而，当自噬进入成熟阶段时，HIV会被降解。不过，这种情况并未发生，因为HIV蛋白Nef通过与自噬调节因子Beclin 1相互作用，充当了一种抗自噬成熟因子，从而保护HIV不被降解。HIV与自噬途径的双重相互作用通过利用自噬早期阶段来提高病毒产量，同时抑制自噬后期阶段。Nef在后者过程中的作用提高了感染性HIV的产量，可能对临床艾滋病的进展具有重要意义。
