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

M. Sarah Hill, Autumn Ruiz, Erik Pacyniak, David M. Pinson, Nathan Culley, Bonnie Yen, Scott Wong, Edward B. Stephens

Research output: Contribution to journalArticle

17 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)86-97
Number of pages12
JournalVirology
Volume371
Issue number1
DOIs
StatePublished - Feb 5 2008

Fingerprint

Simian Immunodeficiency Virus
Macaca
Protein C
HIV-1
Swine
HIV
T-Lymphocytes
vpu Genes
Viruses
gag Gene Products
Viral Load
Membrane Proteins
Cell Culture Techniques
Proteins

Keywords

  • CD4 T-cell depletion
  • Macaques
  • Pathogenesis
  • SHIV
  • Subtype C HIV-1
  • Vpu

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

Cite this

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. / Hill, M. Sarah; Ruiz, Autumn; Pacyniak, Erik; Pinson, David M.; Culley, Nathan; Yen, Bonnie; Wong, Scott; Stephens, Edward B.

In: Virology, Vol. 371, No. 1, 05.02.2008, p. 86-97.

Research output: Contribution to journalArticle

Hill, M. Sarah ; Ruiz, Autumn ; Pacyniak, Erik ; Pinson, David M. ; Culley, Nathan ; Yen, Bonnie ; Wong, Scott ; Stephens, Edward B. / 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. In: Virology. 2008 ; Vol. 371, No. 1. pp. 86-97.
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