Functional analyses of glycosylated gag molecules derived from different gammaretroviruses

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Background Nef is a regulatory lentiviral protein crucial for sustained virus replication in vivo and for disease progression. Among its many activity, Nef downregulates CD4 and MHC-I, activates cellular kinases and enhances virus infectivity. While Nef is uniquely found in the genome of primate lentiviruses, glycosylated gag of MoMLV is an infectivity factor functionally related to Nef, which can rescue the activity of Nef-defective HIV-1. Since ap utative ORF-encoding glycosylated gag can be found in the genome of diverse exogenous and endogenous gammaretroviruses, we investigated whether the Nef-like activity on retrovirus infectivity is conserved in different glycosylated gag alleles and whether such activity can be linked to a conserved featured of the aminoacid sequence. Additionally we are searching for Nef-like factors in other lymphotropic retroviruses which display pathogenic features similar to HIV. Materials and methods We have tested the ability of diverse gammaretroviruses to encode glycosylated gag molecules and analyzed their ability to increase retrovirus infectivity. The activity of glycosylated gag was tested both either in the context of proviral expression or as ectopically over-expressed molecules in HIV-1 producing cells. Expression level and intracellular localization were also studied and compared.