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A Restriction Enzyme Based Cloning Method to Assess the In vitro Replication Capacity of HIV-1 Subtype C Gag-MJ4 Chimeric Viruses
Published on: August 31, 2014
HIV-1 Subtype C Phylodynamics in the Global Epidemic
Vlad Novitsky1,2, Rui Wang3, Stephen Lagakos3
1Department of Immunology and Infectious Diseases, Harvard School of Public Health AIDS Initiative, Harvard School of Public Health, Boston, MA, USA.
Viruses
|October 14, 2011
Summary
HIV-1 subtype C Gag protein shows remarkable stability over time, despite challenges in vaccine development. Selected sites exhibit changes, suggesting population-level selection pressures on this human immunodeficiency virus.
Area of Science:
- Virology
- Immunology
- Genetics
Background:
- Human immunodeficiency virus (HIV) diversity and rapid evolution pose significant hurdles for effective control strategies, including vaccine design.
- Intra-host viral diversification is driven by individual immune responses, while inter-patient transmission creates complex population-level diversity.
- Understanding the evolutionary dynamics of HIV, particularly subtype C, is crucial for developing broadly effective interventions.
Purpose of the Study:
- To analyze the evolutionary trends of HIV-1 subtype C gag sequences over time.
- To identify specific amino acid residues under selection pressure within the Gag protein.
- To assess the stability of HIV-1 subtype C Gag in the context of vaccine development.
Main Methods:
- Retrieved 653 unique HIV-1 subtype C gag sequences from the LANL HIV Database, spanning years <2000 to 2006.
- Grouped sequences by sampling year and analyzed site-specific amino acid residue frequencies.
- Employed phylogenetic analysis and statistical tests (aLRT, trend test, heterogeneity test) to assess sequence diversity and evolutionary changes.
Main Results:
- Median inter-sample diversity of gag sequences was 8.7%.
- Despite overall stability, 4.0% of Gag amino acid residues showed statistically significant changes in frequency over time (>10% range).
- Over half (59.2%) of these changing residues were located within known cytotoxic T-lymphocyte (CTL) epitopes.
Conclusions:
- HIV-1 subtype C Gag protein demonstrates considerable stability in circulating viruses over the past decade.
- Specific Gag sites with changing amino acid frequencies are likely under selection pressure at the population level.
- These findings have implications for HIV vaccine design, highlighting conserved regions and potential targets under immune pressure.
Keywords:
CTL epitopesGagHIV-1 subtype Camino acid frequencyconsensus sequencegag phylogenytime of MRCAMore Related Videos
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