The V1-V3 region of a brain-derived HIV-1 envelope glycoprotein determines macrophage tropism, low CD4 dependence, increased fusogenicity and altered sensitivity to entry inhibitors
2008

HIV-1 Envelope Glycoprotein's Role in Macrophage Infection

publication 10 minutes Evidence: high

Author Information

Author(s): Fiorella Rossi, Bianca Querido, Manideepthi Nimmagadda, Simon Cocklin, Sonia Navas-Martín, Julio Martín-García

Primary Institution: Drexel University College of Medicine

Hypothesis

The V1-V3 region of brain-derived HIV-1 envelope glycoproteins determines their phenotypic differences, including macrophage tropism and CD4 dependence.

Conclusion

The V1-V3 region of brain-derived envelope glycoproteins is crucial for low CD4 dependence, increased macrophage tropism, and altered sensitivity to entry inhibitors.

Supporting Evidence

  • Chimeric Env showed that the V1/V2-C2-V3 region in brain's gp120 determines low CD4 dependence.
  • Brain-derived Env had reduced sensitivity to the fusion inhibitor T-1249.
  • Most low CD4-dependent, macrophage tropic envelopes also had increased sensitivity to the novel entry inhibitor HNG-105.
  • Mutations in the N283 region did not affect the phenotypes of the Env.

Takeaway

This study found that a specific part of the HIV-1 virus helps it infect brain cells better and makes it less dependent on a key receptor, which could help in understanding how HIV affects the brain.

Methodology

Functional studies with chimeric and mutant Env were performed to investigate the viral determinants for phenotypic differences.

Limitations

The study may not fully represent all variations of HIV-1 in different individuals or environments.

Statistical Information

P-Value

p<0.05

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1186/1742-4690-5-89

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