Nguyen, LeAnn
LeAnn is in the Immunity, Microbes, & Molecular Pathogenesis home area of the MBIDP, and joined the CMB training program in 2019. She received a B.S. in Molecular, Cellular, and Developmental Biology from the University of Washington.
Mentor: Dr. Melody Li
The type I (α/β) interferon response forms the crucial first line of defense against pathogens. Host cells produce interferon upon detection of viral invasion, which stimulate expression of antiviral genes known as IFN-stimulated genes (ISGs). One such ISG is the zinc finger antiviral protein (ZAP), which inhibits replication of alphaviruses, retroviruses, filoviruses, and hepatitis B viruses. Known functions of ZAP include recruitment of mRNA degradation machineries and inhibition of viral mRNA translation, as well as recognition and binding of CG dinucleotides. However, the exact mechanism by which ZAP recognizes a specific yet broad range of viruses is still elusive. Among alphaviruses, there is a diversity of sensitivity to the antiviral effects of ZAP: Ross river virus (RRV) and Sindbis virus (SINV) are more sensitive to ZAP than Venezuelan equine encephalitis virus (VEEV), o’nyong’nyong virus (ONNV), and chikungunya virus (CHIKV). Resistant alphaviruses likely contain sequence elements that escape detection by ZAP, but the exact viral sequence elements that are recognized by ZAP remain unknown, as CG dinucleotide motifs are not sufficient to confer sensitivity to ZAP. Additionally, resistant alphaviruses might encode a viral factor that antagonizes ZAP inhibitory activity. Using our panel of related alphaviruses, we will test our hypothesis that ZAP-resistant alphaviruses have evolved strategies to escape detection by ZAP and/or directly antagonize ZAP. Defining viral determinants that confer differential sensitivity to ZAP will elucidate ZAP antiviral mechanism and reveal novel viral strategies of immune defense evasion.
