Heat Shock Protein 70 Family Members Interact with Crimean-Congo Hemorrhagic Fever Virus and Hazara Virus Nucleocapsid Proteins and Perform a Functional Role in the Nairovirus Replication Cycle

摘要: ABSTRACT The Nairovirus genus of the Bunyaviridae family contains serious human and animal pathogens classified within multiple serogroups species. Of these serogroups, Crimean-Congo hemorrhagic fever virus (CCHFV) serogroup comprises sole members CCHFV Hazara (HAZV). is an emerging zoonotic that causes often-fatal in infected humans for which preventative or therapeutic strategies are not available. In contrast, HAZV nonpathogenic to thus represents excellent model study aspects biology under conditions more-accessible biological containment. three RNA segments form nairovirus genome encapsidated by viral nucleocapsid protein (N) ribonucleoprotein (RNP) complexes substrates synthesis packaging into particles. We used quantitative proteomics identify cellular interaction partners N identified robust interactions with chaperones. These were validated using immunological methods, specific between native chaperones HSP70 was confirmed during live infection. Using infectious HAZV, we showed first time N-HSP70 association maintained both cells particles, where assembled as RNPs. Reduction active levels use small-molecule inhibitors significantly reduced titers, a chaperone function context high genetic variability proposed. results suggest required replication represent genetically stable target preventing nairovirus-mediated disease. IMPORTANCE Nairoviruses compose group viruses transmitted ticks associated fatal One member (CCHFV), responsible disease recognized threat Europe response climate change. No against currently Here show related interact protein, HSP70, intracellular extracellular stages life cycle. block reduces titers up 1,000-fold, suggesting this important cycle may potent antinairovirus therapies cannot easily develop resistance.