Document 0506 DOCN M9480506 TI The intracytoplasmic domain of gp41 mediates polarized budding of human immunodeficiency virus type 1 in MDCK cells. DT 9410 AU Lodge R; Gottlinger H; Gabuzda D; Cohen EA; Lemay G; Departement de Microbiologie et Immunologie, Universite de; Montreal, Quebec, Canada. SO J Virol. 1994 Aug;68(8):4857-61. Unique Identifier : AIDSLINE MED/94309148 AB Human immunodeficiency virus type 1 (HIV-1) has been shown to exhibit a specific basolateral release in polarized epithelial cells. Previous investigators have used vaccinia virus recombinants expressing HIV proteins to demonstrate that virus release is nonpolarized in the absence of viral envelope glycoproteins. In this study, we developed a transient expression system which allows the use of Madin-Darby canine kidney polarized epithelial cells directly grown on semipermeable membranes. This procedure allowed us to investigate polarized HIV viral budding following introduction of proviral DNA constructs. Expression of env gene products in trans demonstrated the ability to polarize env-negative viruses in a dose-dependent manner. The targeting signal for polarized virus release was shown to be present in the envelope gp41 transmembrane protein and absent from the gp120 portion of env. At least part of this signal is within the gp41 intracytoplasmic domain. Mutants of the p17gag matrix protein were shown to be nonpolarized only when unable to interact with the envelope glycoproteins. Together, these data are consistent with a model of polarized virus budding in which capsid proteins, lacking a targeting signal, are targeted for specific basolateral release via an interaction of p17 with the envelope glycoprotein containing the polarization signal in its intracytoplasmic domain. DE Animal Biological Transport Cell Line Cloning, Molecular Cytoplasm/METABOLISM Dogs Gene Products, env/PHYSIOLOGY Gene Products, gag/GENETICS/METABOLISM HIV Antigens/GENETICS/METABOLISM HIV Envelope Protein gp41/GENETICS/*PHYSIOLOGY HIV-1/*PHYSIOLOGY Mutation Protein Precursors/PHYSIOLOGY Signal Peptides/METABOLISM Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Virus Replication JOURNAL ARTICLE SOURCE: National Library of Medicine. NOTICE: This material may be protected by Copyright Law (Title 17, U.S.Code).