Abstract
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 SHIVSCVpu, in which the subtype B vpu gene from the pathogenic SHIVKU-1bMC33 was substituted with the vpu from a clinical isolate of subtype C HIV-1 (strain C.96.BW16B01). Cell culture studies revealed that SHIVSCVpu replicated with slightly reduced kinetics when compared with the parental SHIVKU-1bMC33 and that the viral Env and Gag precursor proteins were synthesized and processed similarly compared to the parental SHIVKU-1bMC33. To determine if substitution of the subtype C Vpu protein affected the pathogenesis of the virus, three pig-tailed macaques were inoculated with SHIVSCVpu and circulating CD4+ T-cell levels and viral loads were monitored for up to 44 weeks. Our results show that SHIVSCVpu caused a more gradual decline in the rate of CD4+ T cells in pig-tailed macaques compared to those inoculated with parental subtype B SHIVKU-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.
Original language | English (US) |
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Pages (from-to) | 86-97 |
Number of pages | 12 |
Journal | Virology |
Volume | 371 |
Issue number | 1 |
DOIs | |
State | Published - Feb 5 2008 |
Keywords
- CD4 T-cell depletion
- Macaques
- Pathogenesis
- SHIV
- Subtype C HIV-1
- Vpu
ASJC Scopus subject areas
- Virology