Presence of intact vpu and nef genes in nonpathogenic SHIV is essential for acquisition of pathogenicity of this virus by serial passage in macaques

Glenn A. Mackay, Yafen Niu, Zhen Qian Liu, Sampa Mukherjee, Zhuang Li, Istvan Adany, Shilpa Buch, Wu Zhuge, Harold M. McClure, Opendra Narayan, Marilyn S. Smith

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Use of the macaque model of human immunodeficiency virus (HIV) pathogenesis has shown that the accessory genes nef and vpu are important in the pathogenicity of simian immunodeficiency virus (SIV) and simian-human immunodeficiency virus (SHIV). We examined the ability of two nonpathogenic SHIVs, SHIVPPC and ΔvpuΔnefSHIVPPC, to gain pathogenicity by rapid serial passage in macaques. In this study, each virus was passaged by blood intravenously four times at 4-week intervals in macaques. Animals were monitored for 40 weeks for levels of CD4 T cells and quantitative measures of virus infection. ΔvpuΔnefSHIVPPC maintained a limited phase of productive replication in the four animals, with no loss of CD4+ T cells, whereas SHIVPPC became more pathogenic in later passages, judging by plasma viral load and viral mRNA in lymph nodes, infectious peripheral blood mononuclear cells and CD4+ T cell loss. The nef, LTR, and env of the SHIVPPC viruses underwent numerous mutations, compared to ΔvpuΔnefSHIVPPC. This study confirms the seminal role that nef, LTR, and vpu could play in regulation of pathogenesis of HIV infection.

Original languageEnglish (US)
Pages (from-to)133-146
Number of pages14
JournalVirology
Volume295
Issue number1
DOIs
StatePublished - Jan 1 2002

Fingerprint

vpu Genes
nef Genes
Serial Passage
Simian Immunodeficiency Virus
Macaca
Virulence
HIV
Virus Diseases
Viruses
T-Lymphocytes
Viral Load
Blood Cells
Lymph Nodes
Messenger RNA
Mutation

Keywords

  • HIV
  • Pathogenicity
  • SHIV
  • Vaccine
  • nef
  • vpu

ASJC Scopus subject areas

  • Virology

Cite this

Presence of intact vpu and nef genes in nonpathogenic SHIV is essential for acquisition of pathogenicity of this virus by serial passage in macaques. / Mackay, Glenn A.; Niu, Yafen; Liu, Zhen Qian; Mukherjee, Sampa; Li, Zhuang; Adany, Istvan; Buch, Shilpa; Zhuge, Wu; McClure, Harold M.; Narayan, Opendra; Smith, Marilyn S.

In: Virology, Vol. 295, No. 1, 01.01.2002, p. 133-146.

Research output: Contribution to journalArticle

Mackay, GA, Niu, Y, Liu, ZQ, Mukherjee, S, Li, Z, Adany, I, Buch, S, Zhuge, W, McClure, HM, Narayan, O & Smith, MS 2002, 'Presence of intact vpu and nef genes in nonpathogenic SHIV is essential for acquisition of pathogenicity of this virus by serial passage in macaques', Virology, vol. 295, no. 1, pp. 133-146. https://doi.org/10.1006/viro.2002.1368
Mackay, Glenn A. ; Niu, Yafen ; Liu, Zhen Qian ; Mukherjee, Sampa ; Li, Zhuang ; Adany, Istvan ; Buch, Shilpa ; Zhuge, Wu ; McClure, Harold M. ; Narayan, Opendra ; Smith, Marilyn S. / Presence of intact vpu and nef genes in nonpathogenic SHIV is essential for acquisition of pathogenicity of this virus by serial passage in macaques. In: Virology. 2002 ; Vol. 295, No. 1. pp. 133-146.
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