Since we observed signatures of positive selection for mammalian RTP3 (Table 1) which could be consistent with a role in host defense, we assessed the antiviral potential of mammalian RTP paralogs in mice, humans, and the black flying fox, by ectopic expression in a human hepatoma cell line (Huh7.5) that is permissive to infection by diverse viruses. Here, RTP3 is linked to infection.