25 Years of Ebola Virus VP35 Research

Ebola virus (EBOV) is a highly virulent non-segmented, negative-sense RNA virus and a causative agent of severe, often fatal disease in humans. EBOV encodes 7 genes and viral protein 35 (VP35) plays a key role in EBOV pathogenesis. VP35 is an EBOV polymerase cofactor that facilitates host immune evasion, viral RNA synthesis, and nucleocapsid assembly. Over the past 25 years since the first recognition that VP35 can antagonize innate immune responses, considerable progress has been made to define the molecular mechanisms by which VP35 mediates its multiple functions and interactions with host factors. Much of this work is based on our understanding of the VP35 sequence and structure as it relates to function. Here, we will provide a comprehensive review of the VP35 structure and known insights into function. Given its significant role, VP35 has also emerged as a therapeutic target for the development of countermeasures against EBOV.