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Zika virus (ZIKV), a mosquito-borne positive-stranded RNA virus of the family Flaviviridae (genus Flavivirus), is now causing an unprecedented large-scale outbreak in the Americas. Historically, ZIKV spread eastward from equatorial Africa and Asia to the Pacific Islands during the late 2000s to early 2010s, invaded the Caribbean and Central and South America in 2015, and reached North America in 2016. Although ZIKV infection generally causes no symptoms or only a mild self-limiting illness, it has recently been linked to a rising number of severe neurological diseases, including microcephaly and Guillain-Barré syndrome. Because of the continuous geographic expansion of both the virus and its mosquito vectors, ZIKV poses a serious threat to public health around the globe. However, there are no vaccines or antiviral therapies available against this pathogen. This review summarizes a fast-growing body of literature on the history, epidemiology, transmission, and clinical presentation of ZIKV and highlights the urgent need for the development of efficient control strategies for this emerging pathogen.

The tripartite motif (TRIM) protein family comprises more than 60 members that have diverse functions in various biological processes. Although a small number of TRIM proteins have been shown to regulate innate immunity, much remains to be learned about the functions of the majority of the TRIM proteins. Here we identify TRIM56 as a cellular protein associated with the N-terminal protease (N pro ) of bovine viral diarrhea virus (BVDV), a pestiviral interferon antagonist which degrades interferon regulatory factor 3 (IRF3) through the proteasome. We found that TRIM56 was constitutively expressed in most tissues, and its abundance was further upregulated moderately by interferon or virus. The manipulation of TRIM56 abundance did not affect the protein turnover of N pro and IRF3. Rather, ectopic expression of TRIM56 substantially impaired, while knockdown of TRIM56 expression greatly enhanced, BVDV replication in cell culture. The antiviral activity of TRIM56 depended on its E3 ubiquitin ligase activity as well as the integrity of its C-terminal region but was not attributed to a general augmentation of the interferon antiviral response. Overexpression of TRIM56 did not inhibit the replication of vesicular stomatitis virus or hepatitis C virus, a virus closely related to BVDV. Together, our data demonstrate that TRIM56 is a novel antiviral host factor that restricts pestivirus infection.The tripartite motif (TRIM) protein family consists of more than 60 members that have diverse functions in a broad range of biological processes, including, but not limited to, cell proliferation, differentiation, development, apoptosis, and immunity (19,21). Proteins of the TRIM family share the characteristic tripartite (also known as RBCC) motif that comprises a RING finger, one or two B boxes, and a coiled-coil domain at the N-terminal region. The C-terminal half, however, is variable among different TRIM proteins and can have or not have one or more specific domains that determine the function specificity of some TRIM members. Based on the C-terminal domain composition of the N-terminal RBCC motif, the human TRIMs are classified into 11 subfamilies, subfamilies C-I to C-XI, with the C-IV group having the largest number of members, all of which contain the SPRY/B30.2-like domain, a conserved region whose function remains unclear but is thought to be involved in protein-protein interactions or RNA binding (21,22,29).The functions of the majority of the TRIM proteins are poorly understood. Based on the presence of the RING domain, it was proposed that the TRIM proteins represent a novel class of single-RING-finger E3 ubiquitin (Ub) ligases that mediate the posttranslational modification of different substrates (18). By self-association via the coiled-coil domains, the TRIM proteins oligomerize and act as a scaffold for the assembly of multiprotein complexes that occupy specific cellular compartments (24). TRIM proteins have been shown to be involved in neurological diseases, genetic disorders, and carcinogenesis (18) and have rece...

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