title: Human immunodeficiency virus-1 BF intersubtype recombinant viral protein U second α helix plays an important role in viral release and BST-2 degradation.
abstract: We previously reported a naturally occurring BF intersubtype recombinant viral protein U (Vpu) variant with an augmented capacity to enhance viral replication. Structural analysis of this variant revealed that its transmembrane domain and α-helix I in the cytoplasmic domain (CTD) corresponded to subtype B, whereas the α-helix II in the CTD corresponded to subtype F1. In this study, we aimed to evaluate the role of the Vpu cytoplasmic α-helix II domain in viral release enhancement and in the down-modulation of BST-2 and CD4 from the cell surface. In addition, as serine residues in Vpu amino acid positions 61 or 64 have been shown to regulate Vpu intracellular half-life, which in turn could influence the magnitude of viral release, we also studied the impact of these residues on the VpuBF functions, since S61 and S64 are infrequently found among BF recombinant Vpu variants. Our results showed that the exchange of Vpu α-helix II between subtypes (B→F) directly correlated with the enhancement of viral release and, to a lesser extent, with changes in the capacity of the resulting chimera to down-modulate BST-2 and CD4. No differences in viral release and BST-2 down-modulation were observed between VpuBF and VpuBF-E61S. On the other hand, VpuBF-A64S showed a slightly reduced capacity to enhance viral production, but was modestly more efficient than VpuBF in down-modulating BST-2. In summary, our observations clearly indicate that α-helix II is actively involved in Vpu viral-release-promoting activity and that intersubtype recombination between subtypes B and F1 created a protein variant with a higher potential to boost the spread of the recombinant strain that harbours it.
authors.affiliation: Instituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), Universidad de Buenos Aires, Paraguay 2155 Piso11, C1121AGB Buenos Aires, Argentina.
authors.forename: Cristian
authors.initials: C
authors.lastname: De Candia
authors.affiliation: Instituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), Universidad de Buenos Aires, Paraguay 2155 Piso11, C1121AGB Buenos Aires, Argentina.
authors.forename: Constanza
authors.initials: C
authors.lastname: Espada
authors.affiliation: Instituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), Universidad de Buenos Aires, Paraguay 2155 Piso11, C1121AGB Buenos Aires, Argentina.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Duette
authors.affiliation: Instituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), Universidad de Buenos Aires, Paraguay 2155 Piso11, C1121AGB Buenos Aires, Argentina.
authors.forename: Horacio
authors.initials: H
authors.lastname: Salomón
authors.affiliation: Instituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), Universidad de Buenos Aires, Paraguay 2155 Piso11, C1121AGB Buenos Aires, Argentina.
authors.forename: Mauricio
authors.initials: M
authors.lastname: Carobene
mesh_terms: D015703:Antigens, CD / Q000378:metabolism*; D058851:GPI-Linked Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D005838:Genotype; D015497:HIV-1 / Q000145:classification / Q000235:genetics / Q000472:pathogenicity*; D054298:Human Immunodeficiency Virus Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D059748:Proteolysis; D011995:Recombination, Genetic; D054334:Viral Regulatory and Accessory Proteins / Q000235:genetics / Q000378:metabolism*; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*; D057074:Virus Release; D000074010:Bone Marrow Stromal Antigen 2; D000086082:Viroporin Proteins
chemical_list: D015703:Antigens, CD; D058851:GPI-Linked Proteins; D054298:Human Immunodeficiency Virus Proteins; D054334:Viral Regulatory and Accessory Proteins; D037521:Virulence Factors; C094572:BST2 protein, human; D000074010:Bone Marrow Stromal Antigen 2; C514859:vpu protein, Human immunodeficiency virus 1; D000086082:Viroporin Proteins