Hypophosphorylation of poly(A) polymerase and increased polyadenylation activity are associated with human immunodeficiency virus type 1 Vpr expression.
The HIV-1 encoded accessory protein, viral protein R (Vpr) is responsible for several biological effects in HIV-1-infected cells including nuclear transport of the preintegration complex, activation of long terminal repeat (LTR)-mediated transcription, and the induction of cell-cycle arrest and apoptosis. Vpr's ability to arrest cells at the G2 phase of the cell cycle is due to the inactivation of p34(cdc2) cyclin B complex, resulting in hypophosphorylation of substrates involved in cell-cycle progression from G2 to mitosis (M). Poly(A) polymerase (PAP), the enzyme responsible for poly(A) addition to primary transcripts, contains multiple consensus phosphorylation sites for p34(cdc2) cyclin B kinase that regulates its catalytic activity. We investigated the effects of Vpr on the activity of PAP in Jurkat cells using a superinfection system. Superinfection of cells using Vpr+ vesicular stomatitis virus G protein (VSV-G)-pseudotyped virus caused a complete dephosphorylation of PAP. Cotransfection studies in 293T cells and Xenopus oocyte RNA injection experiments mirrored these effects. Vpr's dramatic effect on PAP dephosphorylation was reflected in enhanced polyadenylation activity in PAP activity assays. HIV-1 Vpr appears to enhance processes that are coupled to transcription such as polyadenylation and could ultimately prove to optimize HIV-1 replication and contribute to HIV-1 pathogenesis. (C)2002 Elsevier Science.
Mouland
Andrew J
AJ
Department of Medicine, McGill University, Lady Davis Institute-Sir Mortimer B Davis Jewish General Hospital, Montreal, Quebec, Canada H3T 1E2. amouland@microimm.mcgill.ca
Coady
Michael
M
Yao
Xiao-Jian
XJ
Cohen
Eric A
EA
D002460:Cell Line; D015967:Gene Expression Regulation, Viral; D016336:Gene Products, vpr / Q000235:genetics / Q000378:metabolism*; D015658:HIV Infections / Q000821:virology; D015497:HIV-1 / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity; D006801:Humans; D019169:Jurkat Cells; D010766:Phosphorylation; D011061:Poly A / Q000378:metabolism; D026723:Polyadenylation; D011062:Polynucleotide Adenylyltransferase / Q000378:metabolism*; D054325:vpr Gene Products, Human Immunodeficiency Virus
D016336:Gene Products, vpr; D054325:vpr Gene Products, Human Immunodeficiency Virus; D011061:Poly A; D011062:Polynucleotide Adenylyltransferase