Abstract
Stress granules (SGs) are cytoplasmic granular aggregations that are induced by cellular stress, including viral infection. SGs have opposing antiviral and proviral roles, which depend on virus species. The exact function of SGs during viral infection is not fully understood. Here, we showed that mumps virus (MuV) induced SGs depending on activation of protein kinase R (PKR). MuV infection strongly induced interferon (IFN)-λ1, 2 and 3, and IFN-β through activation of IFN regulatory factor 3 (IRF3) via retinoic acid inducible gene-I (RIG-I) and the mitochondrial antiviral signaling (MAVS) pathway. MuV-induced IFNs were strongly upregulated in PKR-knockdown cells. MuV-induced SG formation was suppressed by knockdown of PKR and SG marker proteins, Ras-GTPase-activating protein SH3-domain-binding protein 1 and T-cell-restricted intracellular antigen-1, and significantly increased the levels of MuV-induced IFN-λ1. However, viral titer was not altered by suppression of SG formation. PKR was required for induction of SGs by MuV infection and regulated type III IFN (IFN-λ1) mRNA stability. MuV-induced SGs partly suppressed type III IFN production by MuV; however, the limited suppression was not sufficient to inhibit MuV replication in cell culture. Our results provide insight into the relationship between SGs and IFN production induced by MuV infection.
Highlights
Mumps is an infectious disease caused by mumps virus (MuV) and is characterized by swelling of the parotid gland [1]
These results suggested that MuV infection led to moderate shutoff of protein translation, whereas sodium arsenite showed the strong potency of shutoff of protein translation in FL cells (Fig 1C)
Virus titer in the culture supernatants of retinoic acid inducible gene-I (RIG-I)- and mitochondrial antiviral signaling (MAVS)-KD cells significantly increased in comparison to that in control cells, while viral titer was not altered in protein kinase R (PKR)- and melanoma differentiation-associated gene 5 (MDA5)-KD cells (Fig 3D). These results indicated that MuV was recognized by RIG-I but not MDA5, and produced type I and III IFNs through a MAVSand IFN regulatory factor 3 (IRF3)-dependent signal transduction pathway that suppressed viral replication
Summary
Mumps is an infectious disease caused by mumps virus (MuV) and is characterized by swelling of the parotid gland [1]. Mumps has severe characteristic complications such as aseptic meningitis, encephalitis, severe sensory hearing loss, pancreatitis and orchitis. The disease can be prevented by vaccination with attenuated live vaccine, which is used universally in many countries around the world. MuV is an enveloped single negative strand RNA virus that belongs to the PLOS ONE | DOI:10.1371/journal.pone.0161793. Mumps Virus Induces Stress Granules the funders had any role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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