Abstract
Ebola virus (EBOV) genome and mRNAs contain long, structured regions that could hijack host RNA-binding proteins to facilitate infection. We performed RNA affinity chromatography coupled with mass spectrometry to identify host proteins that bind to EBOV RNAs and identified four high-confidence proviral host factors, including Staufen1 (STAU1), which specifically binds both 3' and 5' extracistronic regions of the EBOV genome. We confirmed that EBOV infection rate and production of infectious particles were significantly reduced in STAU1-depleted cells. STAU1 was recruited to sites of EBOV RNA synthesis upon infection and enhanced viral RNA synthesis. Furthermore, STAU1 interacts with EBOV nucleoprotein (NP), virion protein 30 (VP30), and VP35; the latter two bridge the viral polymerase to the NP-coated genome, forming the viral ribonucleoprotein (RNP) complex. Our data indicate that STAU1 plays a critical role in EBOV replication by coordinating interactions between the viral genome and RNA synthesis machinery.IMPORTANCE Ebola virus (EBOV) is a negative-strand RNA virus with significant public health importance. Currently, no therapeutics are available for Ebola, which imposes an urgent need for a better understanding of EBOV biology. Here we dissected the virus-host interplay between EBOV and host RNA-binding proteins. We identified novel EBOV host factors, including Staufen1, which interacts with multiple viral factors and is required for efficient viral RNA synthesis.
Highlights
Ebola virus (EBOV) genome and mRNAs contain long, structured regions that could hijack host RNA-binding proteins to facilitate infection
To begin testing this hypothesis, we performed an RNA affinity chromatography combined with mass spectrometry (RAC-MS) screen to identify host proteins interacting with selected EBOV RNA regions (Fig. 1A)
Our observations further imply an association of STAU1 with the EBOV RNA genome-NPVP35 complex, suggesting that regions of the EBOV genome are available for interaction with trans-acting factors in the presence of NP
Summary
Ebola virus (EBOV) genome and mRNAs contain long, structured regions that could hijack host RNA-binding proteins to facilitate infection. STAU1 interacts with EBOV nucleoprotein (NP), virion protein 30 (VP30), and VP35; the latter two bridge the viral polymerase to the NP-coated genome, forming the viral ribonucleoprotein (RNP) complex. The RNA genome is tightly encapsidated by viral nucleoprotein (NP) oligomers and closely associated with the viral RNA synthesis machinery, which is composed of the viral RNA-dependent RNA polymerase (L), the polymerase cofactor virion protein 35 (VP35), and the transcription activator VP30 [7] Together, they form a multiprotein-RNA complex, termed the viral ribonucleoprotein (RNP) complex [8]. EBOV must have evolved a comprehensive strategy to regulate its RNA synthesis, coordinating viral mRNA transcription, genome replication, and viral RNP assembly; host factors participating in these processes are poorly understood
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