Abstract
The positive-sense, single-stranded RNA alphaviruses pose a potential epidemic threat. Understanding the complex interactions between the viral and the host cell proteins is crucial for elucidating the mechanisms underlying successful virus replication strategies and for developing specific antiviral interventions. Here we present the first comprehensive protein-protein interaction map between the proteins of Semliki Forest Virus (SFV), a mosquito-borne member of the alphaviruses, and host cell proteins. Among the many identified cellular interactors of SFV proteins, the enrichment of factors involved in translation and nonsense-mediated mRNA decay (NMD) was striking, reflecting the virus' hijacking of the translation machinery and indicating viral countermeasures for escaping NMD by inhibiting NMD at later time points during the infectious cycle. In addition to observing a general inhibition of NMD about 4 hours post infection, we also demonstrate that transient expression of the SFV capsid protein is sufficient to inhibit NMD in cells, suggesting that the massive production of capsid protein during the SFV reproduction cycle is responsible for NMD inhibition.
Highlights
As we live through the current SARS-COV2 pandemic, the world is reminded of the unpredictable nature of viral epidemics and the importance of studying potential emerging viral threats
Elucidating these viral–host cell protein interactions is key for understanding the mechanisms that a virus applies to successfully hijack the host cell
This study provides the first comprehensive protein– protein interaction map between the proteins of Semliki Forest Virus (SFV), a positivestrand, single-stranded RNA virus of the alphavirus family
Summary
As we live through the current SARS-COV2 pandemic, the world is reminded of the unpredictable nature of viral epidemics and the importance of studying potential emerging viral threats. The outbreak potential of alphaviruses has already been showcased by the two worldwide epidemics caused by Chikungunya virus (CHIKV) that affected more than 8 million people in over 50 countries and could be attributed to a single point mutation leading to a 100-fold increase in infectious virus in the salivary glands of urban mosquitoes [1,2]. This demonstrates that small genetic alterations can cause dramatic changes in human transmissibility and infection. Though mostly associated with mild febrile illness or asymptomaticity in humans, SFV is endemic to African regions [1] and a handful of studies indicate serious disease relevant symptoms associated with SFV in humans, including encephalitis, myalgia and arthralgia [5,6,7,8]
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