Modulation of the severe CD4⁺ T-cell loss caused by a pathogenic simian–human immunodeficiency virus by replacement of the subtype B vpu with the vpu from a subtype C HIV-1 clinical isolate

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• 作者：M. Sarah Hill ; Autumn Ruiz ; Erik Pacyniak ; David M. Pinson ; Nathan Culley ; Bonnie Yen ; Scott W. Wong ; Edward B. Stephens
• 关键词：Vpu ; SHIV ; Macaques ; Pathogenesis ; Subtype C HIV-1 ; CD4⁺ T-cell depletion
• 刊名：Virology
• 出版年：2008
• 出版时间：5 February 2008
• 年：2008
• 卷：371
• 期：1
• 页码：86-97
• 全文大小：1766 K

文摘

Previously, we showed that the Vpu protein from subtype C human immunodeficiency virus type 1 (HIV-1) was efficiently targeted to the cell surface, suggesting that this protein has biological properties that differ from the well-studied subtype B Vpu protein. In this study, we have further analyzed the biological properties of the subtype C Vpu protein. Flow cytometric analysis revealed that the subtype B Vpu (strain HXB2) was more efficient at down-regulating CD4 surface expression than the Vpu proteins from four subtype C clinical isolates. We constructed a simian-human immunodeficiency virus virus, designated as SHIV_SCVpu, in which the subtype B vpu gene from the pathogenic SHIV_KU-1bMC33 was substituted with the vpu from a clinical isolate of subtype C HIV-1 (strain C.96.BW16B01). Cell culture studies revealed that SHIV_SCVpu replicated with slightly reduced kinetics when compared with the parental SHIV_KU-1bMC33 and that the viral Env and Gag precursor proteins were synthesized and processed similarly compared to the parental SHIV_KU-1bMC33. To determine if substitution of the subtype C Vpu protein affected the pathogenesis of the virus, three pig-tailed macaques were inoculated with SHIV_SCVpu and circulating CD4⁺ T-cell levels and viral loads were monitored for up to 44 weeks. Our results show that SHIV_SCVpu caused a more gradual decline in the rate of CD4⁺ T cells in pig-tailed macaques compared to those inoculated with parental subtype B SHIV_KU-1bMC33. These results show for the first time that different Vpu proteins of HIV-1 can influence the rate at which CD4⁺ T-cell loss occurs in the SHIV/pig-tailed macaque model.