FIG. 5.

Fitness of HIV-1 group O and M WT and derivative drug-resistant mutants. Pairwise competitions were performed among 14 different group O viruses and also the NL4-3-derived viruses. The production of each virus in a dual infection (f₀) was divided by the initial proportion of the inocula (i₀) to determine the relative fitness (W = f₀/i₀). (A) Mean relative fitness of group O mutants relative to the wild type (blue bars) and total relative fitness (red bars). Mean relative fitness was calculated from direct competition against only the wild-type group O CMO2.41 clone, whereas mean relative fitness was derived from the average for 13 competitions performed against a specific strain. Each virus is identified by amino acid sequence at positions 181, 98, 103, and 179 but contains CMO.2.41 sequence for the remainder of the genome. Amino acids in red text represent an NNRTI-resistant codon, and black text represents an NNRTI-sensitive codon. The amino acids boxed by a green line represent the change introduced by site-directed mutagenesis. (B) Mean relative fitness of group M (NL4-3) mutants (Y181 and C181) relative to the WT and the total relative fitness are represented as blue and red bars, respectively. (C and D) Fitness rank order of HIV-1 group O NNRTI mutants is illustrated by a transitive relationship. Ten of the 14 mutants formed a transitive chain (shown in panel C), while four others formed a separate chain (D); intermediate relationships are also shown. The red, orange, and yellow arrows represent transitive relationships and point from the more fit to the less fit viruses. As indicated in the key, the “heat map” and the thickness of the arrow lines indicate the relative ability of one virus to outcompete another. The yellow, orange, and red represent transitive competitions, and the “cooler” blue arrows (light to dark blue) represent fallout competitions of this transitive chain in the pairwise competition. Six (blue arrows) of 169 competitions were responsible for the inability to form transitive chains by four viruses. Thick, thicker, and thickest arrows represent total relative fitness values of between 1 and 2, 2 and 20, and 21 and 100, respectively.