Fig. 3.

a A portion of released Zika virions possess ubiquitinated envelope proteins. Zika virus grown in both human and mosquito cells are ubiquitinated to varying degrees with human grown viruses having longer poly-Ub chains while mosquito-grown viruses retain shorter poly-Ub chains. b Envelope ubiquitination by TRIM7 enhances Zika virus entry in mammalian, but not mosquito, hosts. Ubiquitination of the Zika envelope protein at site K38 is made possible by the E3 ubiquitin ligase TRIM7 allowing for enhanced Zika tissue tropism where levels of TRIM7 are high (brain, uterus, and testis). c Ubiquitination of Zika envelope promotes binding to host receptors and enhances viral entry. The K63-poly-Ub chains of Zika envelope afford for stronger interactions with host receptors (#1), virus-endosome membrane fusion (#2), and higher replication titers (#3). Upon Zika infection, TRIM7 re-localizes to the Golgi and co-localizes with Zika envelope in distinct puncta where ubiquitination presumably occurs. Infectious Zika virions with ubiquitinated envelope can be neutralized with K63-regulate innate immune responses in both a positive and negative manner. TRIM7 promotes herpes virus infection by targeting STING for K48-poly-Ub and proteasome-mediated degradation (#5) while hindering norovirus replication (#6). Additionally, TRIM7 can also enhance TLR4 signaling in macrophages during LPS challenge (#7)