P body-associated protein Mov10 inhibits HIV-1 replication at multiple stages.
Recent studies have shown that APOBEC3G (A3G), a potent inhibitor of human immunodeficiency virus type 1 (HIV-1) replication, is localized to cytoplasmic mRNA-processing bodies (P bodies). However, the functional relevance of A3G colocalization with P body marker proteins has not been established. To explore the relationship between HIV-1, A3G, and P bodies, we analyzed the effects of overexpression of P body marker proteins Mov10, DCP1a, and DCP2 on HIV-1 replication. Our results show that overexpression of Mov10, a putative RNA helicase that was previously reported to belong to the DExD superfamily and was recently reported to belong to the Upf1-like group of helicases, but not the decapping enzymes DCP1a and DCP2, leads to potent inhibition of HIV-1 replication at multiple stages. Mov10 overexpression in the virus producer cells resulted in reductions in the steady-state levels of the HIV-1 Gag protein and virus production; Mov10 was efficiently incorporated into virions and reduced virus infectivity, in part by inhibiting reverse transcription. In addition, A3G and Mov10 overexpression reduced proteolytic processing of HIV-1 Gag. The inhibitory effects of A3G and Mov10 were additive, implying a lack of functional interaction between the two inhibitors. Small interfering RNA (siRNA)-mediated knockdown of endogenous Mov10 by 80% resulted in a 2-fold reduction in virus production but no discernible impact on the infectivity of the viruses after normalization for the p24 input, suggesting that endogenous Mov10 was not required for viral infectivity. Overall, these results show that Mov10 can potently inhibit HIV-1 replication at multiple stages.
Burdick
Ryan
R
HIV Drug Resistance Program, National Cancer Institute-Frederick, Viral Mutation Section, Frederick, MD 21702, USA.
Smith
Jessica L
JL
Chaipan
Chawaree
C
Friew
Yeshitila
Y
Chen
Jianbo
J
Venkatachari
Narasimhan J
NJ
Delviks-Frankenberry
Krista A
KA
Hu
Wei-Shau
WS
Pathak
Vinay K
VK
D000071480:APOBEC-3G Deaminase; D002460:Cell Line; D003564:Cytidine Deaminase / Q000502:physiology; D022083:Cytoplasmic Structures / Q000502:physiology / Q000821:virology; D055785:Gene Knockdown Techniques; D049452:Green Fluorescent Proteins / Q000235:genetics; D015497:HIV-1 / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D006367:HeLa Cells; D054884:Host-Pathogen Interactions / Q000235:genetics / Q000502:physiology; D006801:Humans; D011499:Protein Processing, Post-Translational; D020365:RNA Helicases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D019065:Virus Assembly; D014779:Virus Replication / Q000502:physiology*; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000502:physiology
D012333:RNA, Messenger; D034741:RNA, Small Interfering; D012367:RNA, Viral; C485184:enhanced green fluorescent protein; D054301:gag Gene Products, Human Immunodeficiency Virus; D049452:Green Fluorescent Proteins; C530476:Mov10 protein, human; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase; D020365:RNA Helicases