Few amino acid signatures distinguish HIV-1 subtype B pandemic and non-pandemic strains

The Human Immunodeficiency Virus Type I (HIV-1) subtype B comprises approximately 10% of all HIV infections in the world. The HIV-1 subtype B epidemic comprehends a pandemic variant (named B(PANDEMIC)) disseminated worldwide and non-pandemic variants (named B(CAR)) that are mostly restricted to the Caribbean. The goal of this work was the identification of amino acid signatures (AAs) characteristic to the B(CAR) and B(PANDEMIC) variants. To this end, we analyzed HIV-1 subtype B full-length (n = 486) and partial (n = 814) genomic sequences from the Americas classified within the B(CAR) and B(PANDEMIC) clades and reconstructed the sequences of their most recent common ancestors (MRCA). Analysis of contemporary HIV-1 sequences revealed 13 AAs between B(CAR) and B(PANDEMIC) variants (four on Gag, three on Pol, three on Rev, and one in Vif, Vpu, and Tat) of which only two (one on Gag and one on Pol) were traced to the MRCA. All AAs correspond to polymorphic sites located outside essential functional proteins domains, except the AAs in Tat. The absence of stringent AAs inherited from their ancestors between modern B(CAR) and B(PANDEMIC) variants support that ecological factors, rather than viral determinants, were the main driving force behind the successful spread of the B(PANDEMIC) strain.