Mutagenesis of tyrosine and di-leucine motifs in the HIV-1 envelope cytoplasmic domain results in a loss of Env-mediated fusion and infectivity
2011

Mutations in HIV-1 Envelope Affect Fusion and Infectivity

publication 10 minutes Evidence: high

Author Information

Author(s): Sushma Bhakta, Liang Shang, Jessica L Prince, Daniel T Claiborne, Eric Hunter

Primary Institution: Emory Vaccine Center at the Yerkes National Primate Research Center and Department of Pathology and Laboratory Medicine, Emory University

Hypothesis

The conserved tyrosine and di-leucine motifs in the HIV-1 envelope cytoplasmic domain contribute to Env functionality in the viral life cycle.

Conclusion

Mutations in the Y- and LL-motifs of HIV-1 Env can significantly impair viral replication and infectivity.

Supporting Evidence

  • Sequential mutagenesis of the Y- and LL-motifs resulted in a progressive decrease in Env fusogenicity.
  • The Y712C mutation led to a significant increase in surface expression of Env.
  • Mutants with multiple changes in the LLP2 region exhibited the most dramatic effects on viral infectivity.

Takeaway

Scientists changed some parts of the HIV virus to see how it affects its ability to infect cells, and found that certain changes made it much harder for the virus to work.

Methodology

The study used progressive mutagenesis to alter the Y- and LL-motifs in the HIV-1 Env cytoplasmic domain and assessed the effects on surface expression, fusogenicity, and viral infectivity.

Limitations

The study primarily focused on specific motifs and may not account for all factors influencing HIV-1 Env functionality.

Statistical Information

P-Value

p<0.001

Statistical Significance

p<0.001

Digital Object Identifier (DOI)

10.1186/1742-4690-8-37

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