title: The membrane-proximal intracytoplasmic tyrosine residue of HIV-1 envelope glycoprotein is critical for basolateral targeting of viral budding in MDCK cells.
abstract: Budding of retroviruses from polarized epithelial Madin-Darby canine kidney cells (MDCK) takes place specifically at the basolateral membrane surface. This sorting event is suspected to require a specific signal harbored by the viral envelope glycoprotein and it was previously shown that, as for most basolateral proteins, the intracytoplasmic domain plays a crucial role in this targeting phenomenon. It is well known that tyrosine-based motifs are a central element in basolateral targeting signals. In the present study, site-directed mutagenesis was used to generate conservative or non-conservative substitutions of each four intracytoplasmic tyrosines of the human immunodeficiency virus (HIV-1) envelope glycoprotein. This approach revealed that the membrane-proximal tyrosine is essential to ensure both the basolateral localization of envelope glycoprotein and the basolateral targeting of HIV-1 virions. Substitutions of the membrane-proximal tyrosine did not appear to affect incorporation of envelope glycoprotein into the virions, as assayed by virion infectivity and protein content, nor its capability to ensure its role in viral infection, as determined by viral multiplication kinetics. Altogether, these results indicate that the intracytoplasmic domain of the HIV-1 envelope glycoprotein harbors a unique, tyrosine-based, basolateral targeting signal. Such a tyrosine-based targeting signal may play a fundamental role in HIV transmission and pathogenesis.
authors.affiliation: Département de Microbiologie et Immunologie, Université de Montréal,Québec, Canada.
authors.forename: R
authors.initials: R
authors.lastname: Lodge
authors.forename: J P
authors.initials: JP
authors.lastname: Lalonde
authors.forename: G
authors.initials: G
authors.lastname: Lemay
authors.forename: E A
authors.initials: EA
authors.lastname: Cohen
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002460:Cell Line; D002462:Cell Membrane / Q000821:virology; D016764:Cell Polarity; D004285:Dogs; D015700:HIV Envelope Protein gp41 / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D019169:Jurkat Cells / Q000821:virology; D007668:Kidney; D008562:Membrane Glycoproteins; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D014443:Tyrosine; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism; D014771:Virion / Q000378:metabolism; D014779:Virus Replication / Q000502:physiology*
chemical_list: C028391:G protein, vesicular stomatitis virus; D015700:HIV Envelope Protein gp41; D008562:Membrane Glycoproteins; D014759:Viral Envelope Proteins; D014443:Tyrosine