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Mexican HIV-1 Protease Sequence Diversity.
Pedro G Hernandez-Sanchez1,2, Sandra E Guerra-Palomares1, J Rafael Arguello3
1Laboratorio de Genómica Viral y Humana, Facultad de Medicina, Universidad Autónoma de San Luis Potosí, San Luis Potosí, México.
AIDS Research and Human Retroviruses
|September 26, 2019
Summary
This study analyzed 777 HIV protease sequences from Mexico, finding mostly subtype B with six distinct clades. Conserved regions were identified, offering insights into protease function and potential therapeutic targets.
Area of Science:
- Virology
- Molecular Biology
- Genetics
Background:
- Human Immunodeficiency Virus (HIV) protease is crucial for viral maturation and a key target for antiretroviral therapy.
- Limited diversity analysis of HIV protease sequences exists for Latin America, hindering comprehensive understanding of viral evolution in the region.
Purpose of the Study:
- To investigate the genetic diversity of HIV protease sequences in Mexican isolates.
- To identify conserved and variable regions within the protease gene and their potential functional implications.
Main Methods:
- Phylogenetic analysis of 777 HIV protease sequences from Mexico.
- Identification and characterization of conserved, conservative, and physicochemical changes at various protease sites.
- Mapping of variable sites onto a crystallographic structure of HIV protease.
Main Results:
- Predominantly subtype B (776/777 sequences), with one CRF02_AG isolate.
- Phylogenetic analysis revealed six distinct clades with potential geospecific contributions.
- Thirty-three percent of sites were conserved, 25% had conservative substitutions, and 41% exhibited physicochemical changes.
- Conserved regions included the active site, flap domain, and a region near the 60's loop.
- A single isolate displayed an active site mutation (T26S).
Conclusions:
- HIV protease in Mexico is largely conserved, predominantly subtype B, with identifiable clades.
- Understanding protease variability and conserved regions is vital for developing effective antiretroviral therapies and monitoring drug resistance.
- Structural mapping of variable sites provides valuable insights into the functional relevance of mutations in Mexican HIV isolates.
