TY - JOUR
T1 - Autophagy pathway intersects with HIV-1 biosynthesis and regulates viral yields in macrophages
AU - Kyei, George B.
AU - Dinkins, Christina
AU - Davis, Alexander S.
AU - Roberts, Esteban
AU - Singh, Sudha B.
AU - Dong, Chunsheng
AU - Wu, Li
AU - Kominami, Eiki
AU - Ueno, Takashi
AU - Yamamoto, Akitsugu
AU - Federico, Maurizio
AU - Panganiban, Antonito
AU - Vergne, Isabelle
AU - Deretic, Vojo
PY - 2009/7/27
Y1 - 2009/7/27
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=67649585835&partnerID=8YFLogxK
U2 - 10.1083/jcb.200903070
DO - 10.1083/jcb.200903070
M3 - Article
C2 - 19635843
AN - SCOPUS:67649585835
SN - 0021-9525
VL - 186
SP - 255
EP - 268
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 2
ER -