TY - JOUR TI - Mutational resilience of antiviral restriction favors primate TRIM5α in host-virus evolutionary arms races AU - Tenthorey, Jeannette L AU - Young, Candice AU - Sodeinde, Afeez AU - Emerman, Michael AU - Malik, Harmit S A2 - Schoggins, John W A2 - Weigel, Detlef A2 - Berthoux, Lionel VL - 9 PY - 2020 DA - 2020/09/15 SP - e59988 C1 - eLife 2020;9:e59988 DO - 10.7554/eLife.59988 UR - https://doi.org/10.7554/eLife.59988 AB - Host antiviral proteins engage in evolutionary arms races with viruses, in which both sides rapidly evolve at interaction interfaces to gain or evade immune defense. For example, primate TRIM5α uses its rapidly evolving ‘v1’ loop to bind retroviral capsids, and single mutations in this loop can dramatically improve retroviral restriction. However, it is unknown whether such gains of viral restriction are rare, or if they incur loss of pre-existing function against other viruses. Using deep mutational scanning, we comprehensively measured how single mutations in the TRIM5α v1 loop affect restriction of divergent retroviruses. Unexpectedly, we found that the majority of mutations increase weak antiviral function. Moreover, most random mutations do not disrupt potent viral restriction, even when it is newly acquired via a single adaptive substitution. Our results indicate that TRIM5α’s adaptive landscape is remarkably broad and mutationally resilient, maximizing its chances of success in evolutionary arms races with retroviruses. KW - TRIM5α KW - retroviral restriction KW - evolutionary landscape KW - HIV-1 KW - SIV KW - N-MLV JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -