Hiding the evidence: two strategies for innate immune evasion by hemorrhagic fever viruses

► Structural studies demonstrate different mechanisms of viral immune evasion. ► Ebola virus VP35 forms a novel, asymmetric dimer that masks double-stranded RNA. ► Lassa virus NP is, unexpectedly, a double-stranded RNA-specific exonuclease. The innate immune system is one of the first lines of defense against invading pathogens. Pathogens have, in turn, evolved different strategies to counteract these responses. Recent studies have illuminated how the hemorrhagic fever viruses Ebola and Lassa fever prevent host sensing of double-stranded RNA (dsRNA), a key hallmark of viral infection. The ebolavirus protein VP35 adopts a unique bimodal configuration to mask key cellular recognition sites on dsRNA. Conversely, the Lassa fever virus nucleoprotein actually digests the dsRNA signature. Collectively, these structural and functional studies shed new light on the mechanisms of pathogenesis of these viruses and provide new targets for therapeutic intervention.