Mexican HIV-1 Protease Sequence Diversity Article uri icon

abstract

  • Protease is one of three enzymes encoded within HIV%27s pol gene, responsible for the cleavage of viral Gag-Pol polypeptide into mature viral proteins and a target of current anti-retroviral therapy. Protease diversity analysis in Latin America has been lacking in spite of extensive studies of protease-inhibitor resistance mutations. We studied the diversity of 777 Mexican protease sequences and found that all were subtype B except one (CRF02_AG). Phylogenetic analysis suggested the existence of six different clades with geospecific contributions. Thirty-three percent of sites were conserved, 25%25 had conservative substitutions, and 41%25 exhibited physicochemical changes. The most conserved regions surrounded the active site, most of the flap domain, and a region between the 60%27s loop and C-terminal triad. A single sequence exhibited an active site mutation (T26S). Variable sites were mapped to a crystallographic structure, providing further insight into the distribution and functional relevance of variable sites among Mexican isolates. © Copyright 2020, Mary Ann Liebert, Inc.
  • Protease is one of three enzymes encoded within HIV's pol gene, responsible for the cleavage of viral Gag-Pol polypeptide into mature viral proteins and a target of current anti-retroviral therapy. Protease diversity analysis in Latin America has been lacking in spite of extensive studies of protease-inhibitor resistance mutations. We studied the diversity of 777 Mexican protease sequences and found that all were subtype B except one (CRF02_AG). Phylogenetic analysis suggested the existence of six different clades with geospecific contributions. Thirty-three percent of sites were conserved, 25%25 had conservative substitutions, and 41%25 exhibited physicochemical changes. The most conserved regions surrounded the active site, most of the flap domain, and a region between the 60's loop and C-terminal triad. A single sequence exhibited an active site mutation (T26S). Variable sites were mapped to a crystallographic structure, providing further insight into the distribution and functional relevance of variable sites among Mexican isolates. © Copyright 2020, Mary Ann Liebert, Inc.

publication date

  • 2020-01-01