title: The tyrosine-based YXXØ targeting motif of murine leukemia virus envelope glycoprotein affects pathogenesis.
abstract: Retroviruses, such as human and simian immunodeficiency viruses (HIV and SIV), and murine leukemia viruses (MuLV), harbor a tyrosine-based motif in the intracytoplasmic domain of their envelope glycoprotein. This motif can act as an endocytosis signal or as a targeting signal, restricting viral budding at specific cell surface membrane domains. In the present study, proviral DNA of the ecotropic Cas-Br-E strain of MuLV was modified by substitution or deletion of the critical tyrosine residue. Mutant viruses lost basolateral targeting in polarized MDCK epithelial cells while expression level of the glycoprotein at the cell surface was not affected. This suggests that the tyrosine-based motif in MuLV does not act as an endocytosis signal. Only a small delay in the appearance of disease was observed in inoculated mice. In contrast, a striking change in the pathology was observed with enlarged thymus and lymph nodes in animals inoculated with mutant viruses.
authors.affiliation: Département de Microbiologie et Immunologie, Université de Montréal, Montréal, Québec, Canada.
authors.forename: Carole
authors.initials: C
authors.lastname: Danis
authors.forename: Julie
authors.initials: J
authors.lastname: Deschambeault
authors.forename: Sonia
authors.initials: S
authors.lastname: Do Carmo
authors.forename: Eric A
authors.initials: EA
authors.lastname: Cohen
authors.forename: Eric
authors.initials: E
authors.lastname: Rassart
authors.forename: Guy
authors.initials: G
authors.lastname: Lemay
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D016764:Cell Polarity; D004705:Endocytosis; D009052:Leukemia Virus, Murine / Q000737:chemistry / Q000472:pathogenicity*; D051379:Mice; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D014443:Tyrosine; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000502:physiology; D014771:Virion / Q000472:pathogenicity; D014779:Virus Replication
chemical_list: D014759:Viral Envelope Proteins; D014443:Tyrosine