Legend for Supplemental Material

Fig. S1. Central Memory CD4+ T cell gating strategy. To determine the percentage of central memory CD4+ T cell population in peripheral blood mononuclear cells, peripheral blood was stained with antibodies against CD3, CD4, CD8, CD28, CD95, CCR5, and CCR7.

Representative flow cytometric gating strategy to identify central memory CD4+ T cells

(CD3+CD4+CD28+CD95+CCR7+CCR5-) is shown.

Fig. S2. Composite SIVsmE660 tree from all monkeys with permissive TRIM5 alleles. The maximum-likelihood tree depicts the transmitted/founder virus lineages in each infected monkey that are distributed throughout a diverse set of inoculum sequences (black circles). Most viruses from early infection are represented by a monophyletic lineage, except 4236 (grey) and AV48

(blue). Animal designations are indicated. Square symbols represent sequences from monkeys in the heterozygous permissive group, while the circles denote sequences from monkeys in the homozygous permissive group. Sequences from each monkey are displayed as similarly colored symbols. env sequences at ramp-up viremia are denoted by open symbols, while sequences at peak viremia are represented by closed symbols. Asterisks indicate monkeys that were infected with homogeneous T/F viruses.

Sequences in animal AV33 (pink) formed a single lineage in this tree. However, the level of viral diversity in this animal, even after correction for APOBEC mutations, suggests that it may have been infected by 2 or more closely related viral quasispecies (see Table 1).

Occasional long branches, representing 5 or more base changes from the transmitted virus, were observed among the homogeneous monkeys such as 8E9 and 9E9. In these monkeys, a long branch from the most recent common ancestor of the lineages (the T/F virus) was a consequence of APOBEC mediated G-to-A hypermutation. Multiple sequences in 2 of the 10 animals (DBME and AV33X) were extensively hypermutated, thus accounting for the diversity observed in these 2 animals.

Fig. S3. Maximum likelihood and Highlighter analyses of env sequences from monkey

4236. In the maximum likelihood tree, sequences from ramp-up (open symbol) or peak (closed symbol) or from the inoculum (black circles). In the Highlighter alignment, nucleotide polymorphisms are indicated by a colored tic mark (thymine in red, guanine in orange, adenine in green, and cytosine in blue). Monkey 4236 shows evidence of infection by two closely related variants, as indicated by black bars.

Fig. S4. Maximum likelihood and Highlighter analyses of env sequences from monkey

AV48. In the maximum likelihood tree, sequences from ramp-up (open symbol) or peak (closed symbol) or from the inoculum (black circles). In the Highlighter alignment, nucleotide polymorphisms are indicated by a colored tic mark. Monkey AV48 shows evidence of infection by at least 4 viruses in addition to inter-lineage recombinants, as indicated by black bars. R denotes the recombinant lineage clade.