Журнал микробного патогенеза

Crimean-Congo hemorrhagic fever virus nucleocapsid protein augments mRNA translation

Abstract

Mohammad A Mir

Crimean-Congo hemorrhagic fever virus (CCHFV) is a tickborne
nairovirus of the Bunyaviridae family, causing severe
illness with high mortality rates in humans. Here, we
demonstrate that CCHFV nucleocapsid protein (CCHFV-NP)
augments mRNA translation. CCHFV-NP binds to the viral
mRNA 5' untranslated region (UTR) with high affinity. It
facilitates the translation of reporter mRNA both in vivo and in
vitro with the assistance of the viral mRNA 5' UTR. CCHFVNP
equally favors the translation of both capped and
uncapped mRNAs, demonstrating the independence of this
translation strategy on the 5' cap. Unlike the canonical host
translation machinery, inhibition of eIF4F complex, an
amalgam of three initiation factors, eIF4A, eIF4G, and eIF4E,
by the chemical inhibitor 4E1RCat did not impact the CCHFVNP-
mediated translation mechanism. However, the proteolytic
degradation of eIF4G alone by the human Rhinovirus 2A
protease abrogated this translation strategy. Our results
demonstrate that eIF4F complex formation is not required but
eIF4G plays a critical role in this translation mechanism. Our
results suggest that CCHFV has adopted a unique translation
mechanism to facilitate the translation of viral mRNAs in the
host cell cytoplasm where cellular transcripts are competing
or the same translation apparatus.