Genomic Changes and Compartmentalization After a Chimpanzee-to-Human SFV Spillover

Investigators describe a closely linked chimpanzee-to-human simian foamy virus transmission pair (B1–Case 6) with longitudinal, multi-compartment sampling and sequencing to examine viral change after chimpanzee-to-human SFV spillover.

Using complete genomes generated from tissue-culture isolates (including human peripheral blood lymphocytes and throat sampling) and complete genomes obtained from the infected worker (Case 6; sampled in 1998 and 2000) and the source chimpanzee (B1), the authors describe near identity between the human virus (SFVptr_hu6) and the source chimpanzee virus (SFVptr_B1). They report 99.94% nucleotide identity and 99.85% amino-acid identity between the paired complete genomes. Alongside this consensus-level similarity, the paper also describes compartment-specific bet-region variants and regulatory-region changes observed across follow-up specimens.

Genome-to-genome comparisons within the human recipient were presented as showing little short-term divergence over the sampled interval. In complete-genome datasets derived from 1998 and 2000 collections, the authors report only 1–2 SNPs separating SFVptr_hu6 genomes when contrasting peripheral blood lymphocyte–derived sequences with those from throat, or with later blood-derived sequences. They interpret this pattern as high genomic stability across timepoints and across the compartments represented in the complete-genome sampling, while keeping the observation bounded to the years examined. Taken together, these longitudinal comparisons were framed as limited change over that interval.

Within-host diversity analyses then focused on subgenomic bet sequences obtained by nested PCR with clonal sequencing from multiple body sites sampled over several years. The authors report that both network clustering and Bayesian phylogenetic approaches identified a urine-derived bet clade in Case 6 and, separately, a semen-associated cluster that included semen clones along with oral cavity sequences and some peripheral blood lymphocyte sequences. Specimen coverage in these analyses included peripheral blood lymphocytes, throat and saliva (with some collections combined as an oral cavity specimen), as well as urine and semen, with additional chimpanzee specimens used for comparison. The paper presents these patterns as evidence of compartmentalized variant populations within the human host.

To examine whether host editing might contribute to the observed patterns, the investigators analyzed substitution profiles in bet sequences and describe G-to-A substitutions in GG and GA contexts consistent with APOBEC-associated editing, with a higher number of sites in the urine specimen and fewer sites in other Case 6 and chimpanzee specimens. They report a positive association between GG- and GA-context counts (R2 = 0.71) in regression analysis. In the authors’ interpretation, this pattern is consistent with heterogeneous APOBEC-associated editing that differed between hosts (B1 versus Case 6) and also varied by anatomical compartment within Case 6. They characterize these signatures as unevenly distributed across specimens rather than reflecting uniform drift.

Regulatory-region screening added a second layer of within-host heterogeneity in the human recipient. The authors report ΔU3 LTR deletions (282–479 nt) detected in Case 6 peripheral blood lymphocytes starting in 1998, alongside wild-type sequences, with these ΔU3 variants described as absent in other Case 6 body sites and in B1 peripheral blood lymphocytes. They also report a 301-nt Δtas variant in Case 6 detected in semen (1/12/20), peripheral blood lymphocytes (2002 and 2003), and oral cavity (2002), while describing B1 peripheral blood lymphocytes as wild-type for tas with Δtas observed in tissue culture. Across follow-up specimens from Case 6, pol qPCR proviral loads were reported to range from approximately 1.34×10^2 to 1.11×10^4 copies/μg DNA over five years, which the authors describe as generally low and stable. In their synthesis, the authors link near-genome identity, low/stable proviral loads, heterogeneous APOBEC-like signatures, and LTR/tas changes to compartmental replication and persistence and to their discussion of why secondary human-to-human transmission was not observed in this case.

Key Takeaways:

• The authors report near-identical paired complete genomes between a source chimpanzee (B1) and a human recipient (Case 6), alongside limited short-term divergence across the years sampled in complete-genome comparisons.
• Clonal bet analyses were reported to show compartmentalized variant clusters (including urine- and semen-associated patterns) and APOBEC-consistent G-to-A signatures that the authors describe as differing by host and by specimen site.
• ΔU3 LTR and Δtas variants were detected in specific Case 6 specimens/timepoints, and these findings were presented alongside low/stable proviral loads and the authors’ suggestion that the observed changes may contribute to an apparent lack of person-to-person transmission in this case.