HIV infection is due to the sins of the fathers
Primate genomes contain a large number of endogenous retroviruses which encode evolutionarily dynamic proteins that provide intrinsic immunity to retrovirus infections. Both chimpanzee and gorilla genomes harbor more than 100 copies of Pan troglodytes (chimpanzee) endogenous retrovirus (PtERV1), whereas it is absent from the human genome. We report the resurrection of the core protein of a 4-million-year-old endogenous virus from the chimpanzee genome and show that the human variant of the protein can actively prevent infection by this virus. Comparison of individual PtERV1 proviruses in gorilla and chimpanzee genomes suggest that this virus was active 3 to 4 million years ago, after the separation of chimpanzee and human lineages. One mechanism of restriction from retroviral infections is conferred by the TRIM5-alpha protein, which binds to the incoming retrovirus capsid (CA) core and targets it for premature disassembly or destruction. Each primate species encodes a TRIM5-alpha with a different antiviral specificity. The evolutionary branch of TRIM5-alpha leading to the human lineage shows one of the strongest signatures of positive selection, which suggests that at least one major pathogenic retroviral assailant has challenged the human lineage in the past 4 to 5 million years. Taken together, these findings suggest that TRIM5-alpha evolution was shaped by a species-specific history of ancestral retroviral challenges. We tested human TRIM5-alpha restriction of PtERV1 by infecting cells that express an exogenous copy of the gene. Our data show that resistance to PtERV1 comes at a cost because it reduces resistance to other retroviruses, such as HIV-1. Our analyses demonstrate that selection for resistance to one potential retrovirus pathogen could render a host defense gene less capable of inhibiting another virus. We speculate that fixation of a mutation in human TRIM5-alpha, which could have protected early humans from viruses such as PtERV1 in our distant evolutionary past, may be at least partially responsible for our currently poor resistance to HIV-1.
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[...] HIV infection is due to the sins of the fathers [...]