title: A comparative mutational analysis of HIV-1 Vpu subtypes B and C for the identification of determinants required to counteract BST-2/Tetherin and enhance viral egress.
abstract: We have undertaken a genetic strategy to map Vpu regions necessary for BST-2 antagonism and viral egress. This approach is based on our identification of an egress-defective Vpu variant encoded by an HIV-1 subtype C strain. We constructed a series of chimeric Vpu molecules made from the Vpu C variant and Vpu B from a standard laboratory strain. The TM domain from the inactive Vpu C, which contains multiple non-conserved residues, was responsible for a significant decrease in egress activity and BST-2 downregulation, confirming the functional importance of the Vpu TM domain. However, for complete inactivation, both the N-terminus and TM domain from the inactive Vpu C molecule were required, suggesting a new role for the Vpu N-terminus. In addition, determinants in the C-terminus of Vpu B that may be involved in efficient TGN accumulation were also necessary for enhanced viral egress but are missing or non-functional in Vpu C.
authors.affiliation: Vaccine and Gene Therapy Institute, Oregon Health & Science University, 505 NW 185th Ave, Beaverton, OR 97006, USA. dougljan@ohsu.edu
authors.forename: Janet L
authors.initials: JL
authors.lastname: Douglas
authors.forename: Ying
authors.initials: Y
authors.lastname: Bai
authors.forename: Jean K
authors.initials: JK
authors.lastname: Gustin
authors.forename: Ashlee V
authors.initials: AV
authors.lastname: Moses
mesh_terms: D000595:Amino Acid Sequence; D015703:Antigens, CD; D002460:Cell Line; D004252:DNA Mutational Analysis; D058851:GPI-Linked Proteins / Q000037:antagonists & inhibitors; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D054298:Human Immunodeficiency Virus Proteins / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D054334:Viral Regulatory and Accessory Proteins / 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; C094572:BST2 protein, human; D000074010:Bone Marrow Stromal Antigen 2; C514859:vpu protein, Human immunodeficiency virus 1; D000086082:Viroporin Proteins