MLV glycosylated-Gag is an infectivity factor that rescues Nef-deficient HIV-1.
Optimal infectivity of HIV-1 virions requires synthesis of the HIV-1 regulatory protein Nef in some producer cells but not others. A survey of 18 lymphoid cell lines found that Nef was dispensable in three, each of which harbored gammaretroviruses. Nef-dependent cell lines were rendered Nef-independent by a cell-free supernatant from the independent lines or by transfection of cloned murine leukemia virus (MLV). Analysis of MLV deletion mutations identified glycosylated gag (glycogag) as the factor that rescues Nef-defective HIV-1 virions. Glycogag was also demonstrated to be required for the infectivity of MLV virions produced in lymphoid cells. Direct comparison of Nef and glycogag revealed identical dependence for activity on Env-pseudotype and producer cell type. The two proteins colocalize within cells, and both increase the yield of viral cDNA in target cells. The functional similarity of Nef and glycogag is a compelling example of convergent evolution in which two structurally unrelated proteins provide a function necessary for virion infectivity in lymphoid cells.
Pizzato
Massimo
M
Department of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland. massimo.pizzato@unige.ch
D015153:Blotting, Western; D017931:DNA Primers / Q000235:genetics; D004591:Electrophoresis, Polyacrylamide Gel; D019143:Evolution, Molecular; D015683:Gene Products, gag / Q000378:metabolism*; D006031:Glycosylation; D015497:HIV-1 / Q000378:metabolism / Q000472:pathogenicity*; D009052:Leukemia Virus, Murine / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D020133:Reverse Transcriptase Polymerase Chain Reaction; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000172:deficiency*
D017931:DNA Primers; D015683:Gene Products, gag; D054311:nef Gene Products, Human Immunodeficiency Virus; C514837:nef protein, Human immunodeficiency virus 1