PT  - JOURNAL ARTICLE
AU  - Abhilash I. Chiramel
AU  - Nicholas R. Meyerson
AU  - Kristin L. McNally
AU  - Rebecca M. Broeckel
AU  - Vanessa R. Montoya
AU  - Omayra Méndez-Solís
AU  - Shelly J. Robertson
AU  - Gail L. Sturdevant
AU  - Kirk J. Lubick
AU  - Vinod Nair
AU  - Brian H. Youseff
AU  - Robin M. Ireland
AU  - Catharine M. Bosio
AU  - Kyusik Kim
AU  - Jeremy Luban
AU  - Vanessa M. Hirsch
AU  - R. Travis Taylor
AU  - Fadila Bouamr
AU  - Sara L. Sawyer
AU  - Sonja M. Best
TI  - TRIM5α restricts flavivirus replication by targeting the viral protease for proteasomal degradation
AID  - 10.1101/605345
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 605345
4099  - http://biorxiv.org/content/early/2019/04/11/605345.short
4100  - http://biorxiv.org/content/early/2019/04/11/605345.full
AB  - Tripartite motif-containing protein 5α (TRIM5α) functions as a cellular antiviral restriction factor with exquisite specificity towards the capsid lattices of retroviruses. The relative avidity of TRIM5α binding to retrovirus capsids directly impacts primate species susceptibility to infection, but the antiviral role of TRIM5α is thought limited to retroviruses. In contrast to this current understanding, here we show that both human and rhesus TRIM5α possess potent antiviral function against specific flaviviruses through interaction with the viral protease (NS2B/3) to inhibit virus replication. Importantly, TRIM5α was essential for the antiviral function of IFN-I against sensitive flaviviruses in human cells. However, TRIM5α was ineffective against mosquito-borne flaviviruses (yellow fever, dengue, and Zika viruses) that establish transmission cycles in humans following emergence from non-human primates. Thus, TRIM5α is revealed to possess remarkable plasticity in recognition of diverse virus families, with potential to influence human susceptibility to emerging flaviviruses of global concern.