title: Impact of natural polymorphism within the gp41 cytoplasmic tail of human immunodeficiency virus type 1 on the intracellular distribution of envelope glycoproteins and viral assembly.
abstract: The motifs involved in the various functions of the human immunodeficiency virus type 1 (HIV-1) gp41 cytoplasmic tail (CT), particularly those related to the intracellular trafficking and assembly of envelope glycoproteins (Env) onto core particles, have generally been assessed with a restricted panel of T-cell laboratory-adapted virus strains. Here, we investigated gp41 CT sequences derived from individuals infected with HIV-1 viruses of various subtypes. We identified four patients harboring HIV variants with a natural polymorphism in the membrane-proximal tyrosine-based signal Y(712)SPL or the Y(802)W(803) diaromatic motif, which are two major determinants of Env intracellular trafficking. Confocal microscopy showed that the intracellular distribution of Env with a mutation in the tyrosine or diaromatic motif differed from that of Env with no mutation in these motifs. Surprisingly, the gp41 CTs of the primary viruses also had differential effects on the intracellular distribution of Env, independently of mutations in the tyrosine or diaromatic motifs, suggesting the involvement of additional determinants. Furthermore, analyses of virus replication kinetics indicated that the effects of mutations in the tyrosine or diaromatic motifs on viral replication depended on the gp41 CT context. These effects were at least partly due to differences in the efficiency of Env incorporation into virions. Thus, polymorphisms in primary HIV-1 gp41 CTs at the quasispecies or subtype level can influence the intracellular distribution of Env, its incorporation into virions, and viral replication capacity.
authors.affiliation: Université François Rabelais, Tours, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Lambelé
authors.forename: Béatrice
authors.initials: B
authors.lastname: Labrosse
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Roch
authors.forename: Alain
authors.initials: A
authors.lastname: Moreau
authors.forename: Bernard
authors.initials: B
authors.lastname: Verrier
authors.forename: Francis
authors.initials: F
authors.lastname: Barin
authors.forename: Philippe
authors.initials: P
authors.lastname: Roingeard
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Mammano
authors.forename: Denys
authors.initials: D
authors.lastname: Brand
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D015686:Gene Products, env / Q000032:analysis*; D015683:Gene Products, gag / Q000378:metabolism; D015700:HIV Envelope Protein gp41 / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D015658:HIV Infections / Q000821:virology; D015497:HIV-1 / Q000235:genetics* / Q000502:physiology / Q000648:ultrastructure; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D021381:Protein Transport; D016415:Sequence Alignment; D014771:Virion / Q000378:metabolism; D019065:Virus Assembly / Q000235:genetics*; D014779:Virus Replication
chemical_list: D015686:Gene Products, env; D015683:Gene Products, gag; D015700:HIV Envelope Protein gp41