title: Human Ubc9 contributes to production of fully infectious human immunodeficiency virus type 1 virions.
abstract: Ubc9 was identified as a cellular protein that interacts with the Gag protein of Mason-Pfizer monkey virus. We show here that Ubc9 also interacts with the human immunodeficiency virus type 1 (HIV-1) Gag protein and that their interaction is important for virus replication. Gag was found to colocalize with Ubc9 predominantly at perinuclear puncta. While cells in which Ubc9 expression was suppressed with RNA interference produced normal numbers of virions, these particles were 8- to 10-fold less infectious than those produced in the presence of Ubc9. The nature of this defect was assayed for dependence on Ubc9 during viral assembly, trafficking, and Env incorporation. The Gag-mediated assembly of virus particles and protease-mediated processing of Gag and Gag-Pol were unchanged in the absence of Ubc9. However, the stability of the cell-associated Env glycoprotein was decreased and Env incorporation into released virions was altered. Interestingly, overexpression of the Ubc9 trans-dominant-negative mutant C93A, which is a defective E2-SUMO-1 conjugase, suggests that this activity may not be required for interaction with Gag, virion assembly, or infectivity. This finding demonstrates that Ubc9 plays an important role in the production of infectious HIV-1 virions.
authors.affiliation: Nebraska Center for Virology and School of Biological Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583-0900, USA.
authors.forename: Tareq
authors.initials: T
authors.lastname: Jaber
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Bohl
authors.forename: Gentry L
authors.initials: GL
authors.lastname: Lewis
authors.forename: Charles
authors.initials: C
authors.lastname: Wood
authors.forename: John T
authors.initials: JT
authors.lastname: West
authors.forename: Robert A
authors.initials: RA
authors.lastname: Weldon
mesh_terms: D002460:Cell Line; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity; D006367:HeLa Cells; D006801:Humans; D034622:RNA Interference; D014162:Transfection; D044763:Ubiquitin-Conjugating Enzymes / Q000378:metabolism*; D014771:Virion / Q000378:metabolism* / Q000472:pathogenicity; D019065:Virus Assembly; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000378:metabolism*; D000098843:Ubiquitin-Conjugating Enzyme UBC9
chemical_list: D054301:gag Gene Products, Human Immunodeficiency Virus; D044763:Ubiquitin-Conjugating Enzymes; D000098843:Ubiquitin-Conjugating Enzyme UBC9