Pokeweed antiviral protein restores levels of cellular APOBEC3G during HIV-1 infection by depurinating Vif mRNA.
Pokeweed antiviral protein (PAP) is an RNA glycosidase that inhibits production of human immunodeficiency virus type 1 (HIV-1) when expressed in human culture cells. Previously, we showed that the expression of PAP reduced the levels of several viral proteins, including virion infectivity factor (Vif). However, the mechanism causing Vif reduction and the consequences of the inhibition were not determined. Here we show that the Vif mRNA is directly depurinated by PAP. Because of depurination at two specific sites within the Vif ORF, Vif levels decrease during infections and the progeny viruses that are generated are ∼ 10-fold less infectious and compromised for proviral integration. These results are consistent with PAP activity inhibiting translation of Vif, which in turn reduces the effect of Vif to inactivate the host restriction factor APOBEC3G (apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like editing complex 3G). Our findings identify Vif mRNA as a new substrate for PAP and demonstrate that derepression of innate immunity against HIV-1 contributes to its antiviral activity.
Department of Biology, York University, Toronto, Ontario, Canada.
Gabriela
G
Krivdova
Department of Biology, York University, Toronto, Ontario, Canada. Electronic address: hudak@yorku.ca.
Katalin A
KA
Hudak
D000071480:APOBEC-3G Deaminase; D003564:Cytidine Deaminase / Q000235:genetics* / Q000378:metabolism; D057809:HEK293 Cells; D015658:HIV Infections / Q000821:virology; D015497:HIV-1 / Q000235:genetics* / Q000502:physiology; D006801:Humans; D016366:Open Reading Frames; D011685:Purine Nucleotides / Q000172:deficiency* / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism*; D012367:RNA, Viral / Q000378:metabolism*; D054788:Ribosome Inactivating Proteins / Q000235:genetics; D054789:Ribosome Inactivating Proteins, Type 1 / Q000235:genetics / Q000378:metabolism*; D054320:vif Gene Products, Human Immunodeficiency Virus / Q000235:genetics* / Q000378:metabolism
D011685:Purine Nucleotides; D012333:RNA, Messenger; D012367:RNA, Viral; D054789:Ribosome Inactivating Proteins, Type 1; D054320:vif Gene Products, Human Immunodeficiency Virus; D054788:Ribosome Inactivating Proteins; C024275:pokeweed antiviral protein; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase
APOBEC3G; HIV-1; Pokeweed antiviral protein; RNA glycosidase; Ribosome-inactivating protein; Vif