Retroviral origins of antiviral proteins
Sequences of retroviral origins are abundant in the human genome, but their functional significance remains poorly understood. Frank et al. identified a pool of sequences derived from retroviral envelopes (which normally facilitate viral entry into cells) that are expressed during human fetal development, viral infection, and immune stimulation (see the Perspective by Padilla Del Valle and McLaughlin). The authors hypothesized that some of these sequences encode proteins with antiviral activity by binding to and competing for cell surface receptors targeted by infectious viruses. Genetic manipulation in cell culture showed that one such protein, SUPYN, was capable of restricting infection by type D retroviruses circulating in several mammals. —DJ
Abstract
Endogenous retroviruses are abundant components of mammalian genomes descended from ancient germline infections. In several mammals, the envelope proteins encoded by these elements protect against exogenous viruses, but this activity has not been documented with endogenously expressed envelopes in humans. We report that the human genome harbors a large pool of envelope-derived sequences with the potential to restrict retroviral infection. To test this, we characterized an envelope-derived protein, Suppressyn. We found that Suppressyn is expressed in human preimplantation embryos and developing placenta using its ancestral retroviral promoter. Cell culture assays showed that Suppressyn, and its hominoid orthologs, could restrict infection by extant mammalian type D retroviruses. Our data support a generalizable model of retroviral envelope co-option for host immunity and genome defense.
