HIV-1 production is specifically associated with human NMT1 long form in human NMT isozymes.
The N-myristoylation of the N-terminal of human immunodeficiency virus type-1 (HIV-1) Pr55(gag) by human N-myristoyltransferase (hNMT) is a prerequisite modification for HIV-1 production. hNMT consists of multiple isozymes encoded by hNMT1 and hNMT2. The hNMT1 isozyme consists of long, medium, and short forms. Here, we investigated which isozyme is crucial for HIV-1 production. Human embryonic kidney (HEK) 293 cells transfected with infectious HIV-1 vectors were used as models of HIV-1-infected cells in this study. The significant reduction in HIV-1 production and the failure of the specific localization of Pr55(gag) in a detergent-resistant membrane fraction were dependent on the knockdown of the different forms of the hNMT1 isozyme but not of the hNMT2 isozyme. Additionally, the coexpression of an inactive mutant hNMT1 isozyme, namely the hNMT1 long form (hNMT1(L)), but not that of other hNMT mutants resulted in a significant reduction in HIV-1 production. These results strongly suggest that HIV-1 production is specifically associated with hNMT1, particularly hNMT1(L), but not with hNMT2 in vivo, contributing to the understanding of a step in HIV-1 replication.
Takamune
Nobutoki
N
Department of Pharmaceutical Biochemistry, Faculty of Medical and Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-Honmachi, Kumamoto 862-0973, Japan.
Gota
Kayoko
K
Misumi
Shogo
S
Tanaka
Kenzo
K
Okinaka
Shigetaka
S
Shoji
Shozo
S
D000217:Acyltransferases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002458:Cell Fractionation; D002460:Cell Line; D002462:Cell Membrane / Q000737:chemistry; D002470:Cell Survival; D020868:Gene Silencing; D016655:HIV Core Protein p24 / Q000096:biosynthesis; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D011498:Protein Precursors / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D014779:Virus Replication / Q000502:physiology
D016655:HIV Core Protein p24; D007527:Isoenzymes; D050505:Mutant Proteins; D011498:Protein Precursors; D012333:RNA, Messenger; C059767:p55 gag precursor protein, Human immunodeficiency virus 1; D000217:Acyltransferases; C050480:glycylpeptide N-tetradecanoyltransferase