title: Wild-type levels of human immunodeficiency virus type 1 infectivity in the absence of cellular emerin protein.
abstract: Preintegration complexes (PICs) mediate retroviral integration, and recent results indicate an important role for the inner nuclear membrane protein emerin in orienting human immunodeficiency virus type 1 (HIV-1) PICs to chromatin for integration. Two other host cell proteins, the barrier-to-autointegration factor (BAF) and lamina-associated polypeptide 2alpha (LAP2alpha), seemed to play a similar preintegrative role for Moloney murine leukemia virus (MMLV) in addition to HIV-1. In contrast, we determined efficient HIV-1 and MMLV infection of HeLa-P4 cells following potent down-regulation of emerin, BAF, or LAP2alpha protein by using short interfering RNA. Mouse embryo fibroblasts ablated for emerin protein through gene knockout support the same level of HIV-1 infection as cells derived from wild-type littermate control animals. As the expression of human emerin in mouse knockout cells fails to affect the level of infectivity achieved in its absence, we conclude that HIV-1 efficiently infects cells in the absence of emerin protein and, by extension, that emerin is not a universally important regulator of HIV-1 infectivity.
authors.affiliation: Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, 44 Binney St., Boston, MA 02115, USA.
authors.forename: Ming-Chieh
authors.initials: MC
authors.lastname: Shun
authors.forename: Janet E
authors.initials: JE
authors.lastname: Daigle
authors.forename: Nick
authors.initials: N
authors.lastname: Vandegraaff
authors.forename: Alan
authors.initials: A
authors.lastname: Engelman
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D015497:HIV-1 / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D034904:Lamin Type A / Q000235:genetics / Q000378:metabolism; D009052:Leukemia Virus, Murine / Q000472:pathogenicity; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D016415:Sequence Alignment
chemical_list: C501959:BANF1 protein, human; D004268:DNA-Binding Proteins; D034904:Lamin Type A; D008565:Membrane Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; C092710:emerin; C093413:lamina-associated polypeptide 2