The membrane-proximal intracytoplasmic tyrosine residue of HIV-1 envelope glycoprotein is critical for basolateral targeting of viral budding in epithelial cells.
Int Conf AIDS 1996 Jul 7-12; 11:228 (abstract no. Tu.A.495) Cohen EA, Lodge R, Lalonde JP, Lemay G; Department de Microbiologie et Immunologie, Universite de Montreal, Montreal, Quebec, Canada. Fax: 514-343-5995.
Budding of retroviruses from infected cells takes place specifically at the basolateral membrane surface of polarized epithelial Madin-Darby canine kidney cells (MDCK). This sorting event is suspected to require a specific signal harbored by the viral glycoprotein envelope and we previously showed 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, we used site-directed mutagenesis to generate conservative or non-conservative substitution of each four envelope glycoprotein intracytoplasmic tyrosines of human immunodeficiency virus (HIV-1). The membrane-proximal tyrosine is essential to ensure basolateral targeting of HIV-1 virions. Substitutions of the membrane-proximal tyrosine did not appear to affect incorporation of envelope glycoprotein to the virions nor its capability to ensure its role in viral infection. The effect of the four accessory HIV-1 proteins nef, vif, vpu and vpr was also examined and it was clearly shown that they are not involved in basolateral targeting.
Keywords: AEGIS, HIV-1, Tyrosine, Glycoproteins, Virion, Epithelial Cells, Cell Line, Protein Transport, Biological Transport, Cell Membrane, Membranes, Mutagenesis, Site-Directed, Animal, Dogs, Human, virology, ICA11
