title: Processing, fusogenicity, virion incorporation and CXCR4-binding activity of a feline immunodeficiency virus envelope glycoprotein lacking the two conserved N-glycosylation sites at the C-terminus of the V3 domain.
abstract: The process of feline immunodeficiency virus (FIV) entry into its target cells is initiated by the association of the surface (SU) subunit of the viral envelope glycoprotein (Env) with the cellular receptors CD134 and CXCR4. This event is followed by the fusion of the viral and cellular membranes, which is mediated by the transmembrane (TM) subunit of Env. We and others have previously demonstrated that the V3 domain of the SU subunit of Env is essential for CXCR4 binding. Of note, there are two contiguous and highly conserved potential N-glycosylation sites ((418)NST(420) and (422)NLT(424)) located at the C-terminal side of the V3 domain. We therefore decided to study the relevance for Env functions of these N-glycosylation motifs and found that disruption of both of them by introducing the N418Q/N422Q double amino acid substitution drastically impairs Env processing into the SU and TM subunits. Moreover, the simultaneous mutation of these N-glycosylation sites prevents Env incorporation into virions and Env-mediated cell-to-cell fusion. Notably, a recombinant soluble version of the SU glycoprotein carrying the double amino acid replacement N418Q/N422Q at the V3 C-terminal side binds to CXCR4 with an efficiency similar to that of wild-type SU.
authors.affiliation: Laboratorio de Virología, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), University of Belgrano (UB), Villanueva 1324, C1426BMJ, Buenos Aires, Argentina.
authors.forename: Silvia A
authors.initials: SA
authors.lastname: González
authors.affiliation: Laboratorio de Virología, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), University of Belgrano (UB), Villanueva 1324, C1426BMJ, Buenos Aires, Argentina. jose.affranchino@comunidad.ub.edu.ar.
authors.forename: José L
authors.initials: JL
authors.lastname: Affranchino
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D002415:Cats; D016181:Feline Acquired Immunodeficiency Syndrome / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D006031:Glycosylation; D016089:Immunodeficiency Virus, Feline / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D000072417:Protein Domains; D046188:Protein Modification, Translational; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism*; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D008562:Membrane Glycoproteins; D019718:Receptors, CXCR4; D014759:Viral Envelope Proteins