Functional domains within the human immunodeficiency virus type 2 envelope protein required to enhance virus production.
Primate lentiviruses code for a protein that stimulates virus production. In human immunodeficiency virus type 1 (HIV-1), the activity is provided by the accessory protein, Vpu, while in HIV-2 and simian immunodeficiency virus it is a property of the envelope (Env) glycoprotein. Using a group of diverse retroviruses and cell types, we have confirmed the functional equivalence of the two proteins. However, despite these similarities, the two proteins have markedly different functional domains. While the Vpu activity is associated primarily with its membrane-spanning region, we have determined that the HIV-2 Env activity requires both the cytoplasmic tail and ectodomain of the protein, with the membrane-spanning domain being less important. Within the Env cytoplasmic tail, we further defined the necessary sequence as a membrane-proximal tyrosine-based motif. Providing the two Env regions separately as distinct CD8 chimeric proteins did not increase virus release. This suggests that the two domains must be either contained within a single protein or closely associated within a multiprotein oligomer, such as the Env trimer, in order to function. Finally, we observed that wild-type levels of incorporation of the HIV-2 Env into budding viruses were not required for this activity.
Abada
Paolo
P
Department of Biochemistry and Molecular Biology, Childrens Hospital Los Angeles, 4650 Sunset Blvd., Mailstop 62, Los Angeles, CA 90027, USA.
Noble
Beth
B
Cannon
Paula M
PM
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002459:Cell Fusion; D002460:Cell Line; D015686:Gene Products, env / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D015498:HIV-2 / Q000235:genetics* / Q000254:growth & development*; D006367:HeLa Cells; D054298:Human Immunodeficiency Virus Proteins; D006801:Humans; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D054334:Viral Regulatory and Accessory Proteins / Q000235:genetics / Q000502:physiology; D014771:Virion / Q000378:metabolism; D014779:Virus Replication; D000086082:Viroporin Proteins
D015686:Gene Products, env; D054298:Human Immunodeficiency Virus Proteins; D054334:Viral Regulatory and Accessory Proteins; C514859:vpu protein, Human immunodeficiency virus 1; D000086082:Viroporin Proteins
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