Second, control co-culture PERV transmission events were exceptionally diverse, as 11 unique pol sequences were detected and only 4 were found multiple times (Online Figure S4) . These data suggested that PK-15 cells have at least 11 active PERVs capable of infecting human 293T cells, a number consistent with previous studies that reported the existence of approximately 17-50 PERV copies in total (with only a fraction being replicationcompetent; [11, 12] ). In contrast, the rare PERV sequences derived from the APOBEC3G co-culture experiments showed a much lower genetic complexity. Only three unique sequences were recovered, each differing by a single nucleotide (Online Figure S4) . In parallel experiments with HIV-based viruses, this APOBEC3G expression construct caused approximately 30 G-to-A hypermutations per 1000 bases analyzed (e.g., [41] ). Thus, approximately 12 G-to-A transitions should have been recovered in these PERV DNA analyses (nearly 90 if multiply recovered sequences would have been considered). The absence of hypermutated PERV proviral DNA provided further support for a deaminase-independent mechanism of restriction, which may share features with other instances described previously (e.g., [27] [28] [29] [30] ).