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Updated: Aug 15, 2026

Analysis of Simian Immunodeficiency Virus-specific CD8+ T-cells in Rhesus Macaques by Peptide-MHC-I Tetramer Staining
06:25

Analysis of Simian Immunodeficiency Virus-specific CD8+ T-cells in Rhesus Macaques by Peptide-MHC-I Tetramer Staining

Published on: December 23, 2016

A single amino acid change and truncated TM are sufficient for simian immunodeficiency virus to enter cells using

A Bonavia1, B T Bullock, K M Gisselman

  • 1Retrovirus Biology Laboratory, Department of Comparative Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Virology
|August 3, 2005
PubMed

Insights

Researchers studied Simian Immunodeficiency Virus (SIV) cell entry using a novel cell line. They found specific mutations in the SIV envelope transmembrane protein (TM) are key to CD4-independent entry and neurovirulence.

Area of Science:

  • Virology
  • Immunology
  • Molecular Biology

Background:

  • Entry of Human Immunodeficiency Virus (HIV) and Simian Immunodeficiency Virus (SIV) into host cells requires CD4 and chemokine receptors as coreceptors.
  • Understanding SIV cell entry mechanisms is crucial for developing antiviral strategies and comprehending viral pathogenesis.

Purpose of the Study:

  • To investigate the cell entry mechanisms of macrophage-tropic SIV strains.
  • To identify viral determinants responsible for CD4-independent entry and neurovirulence.

Main Methods:

  • Development of a novel SIV-susceptible reporter cell line (xKLuSIV) from human K562 cells.
  • Infection assays using macrophage-tropic SIV strains (SIV/17E-Fr and SIV/17E-Cl) with engineered xKLuSIV cells expressing CD4 and/or CCR5.
  • Analysis of viral entry mechanisms using receptor blocking (AOP-RANTES) and antibody neutralization.
  • Characterization of viral envelope (env) gene mutants, focusing on the transmembrane (TM) protein, to determine CD4 independence determinants.

Main Results:

  • xKLuSIV cells expressing both rhesus CD4 and CCR5 were susceptible to SIV infection.
  • The neurovirulent SIV/17E-Fr strain exhibited CD4-independent entry mediated by CCR5, while the non-neurovirulent SIV/17E-Cl required both CD4 and CCR5.
  • Truncation of the TM protein at amino acid 764 and a specific amino acid change (R751G) conferred CD4-independent entry to SIV/17E-Fr.

Conclusions:

  • The envelope of the neurovirulent SIV/17E-Fr strain interacts with CCR5 independently of CD4.
  • Specific alterations within the SIV TM protein are critical determinants for CD4-independent viral entry and contribute to neurovirulence.

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