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Dissecting Host-virus Interaction in Lytic Replication of a Model Herpesvirus
Published on: October 7, 2011
The V protein of mumps virus plays a critical role in pathogenesis
Pei Xu1, Priya Luthra, Zhuo Li
1Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, Georgia, USA.
Abstract:
Mumps virus (MuV) causes an acute infection in humans characterized by a wide array of symptoms ranging from relatively mild manifestations, such as parotitis, to more-severe complications, such as meningitis and encephalitis. Widespread mumps vaccination has reduced mumps incidence dramatically; however, outbreaks still occur in vaccinated populations. The V protein of MuV, when expressed in cell culture, blocks interferon (IFN) expression and signaling and interleukin-6 (IL-6) signaling. In this work, we generated a recombinant MuV incapable of expressing the V protein (rMuVΔV). The rescued MuV was derived from a clinical wild-type isolate from a recent outbreak in the United States (MuV(Iowa/US/06), G genotype). Analysis of the virus confirmed the roles of V protein in blocking IFN expression and signaling and IL-6 signaling. We also found that the rMuV(Iowa/US/06)ΔV virus induced high levels of IL-6 expression in vitro, suggesting that V plays a role in reducing IL-6 expression. In vivo, the rMuV(Iowa/US/06)ΔV virus was highly attenuated, indicating that the V protein plays an essential role in viral virulence.
Insights
Mumps virus (MuV) V protein blocks interferon and IL-6 signaling. Removing V protein (rMuVΔV) from a clinical isolate enhanced IL-6 and reduced viral virulence, highlighting V
Area of Science:
- Virology
- Immunology
Background:
- Mumps virus (MuV) causes diverse symptoms, from parotitis to meningitis.
- Mumps outbreaks persist despite widespread vaccination.
- The MuV V protein inhibits interferon (IFN) and interleukin-6 (IL-6) signaling.
Purpose of the Study:
- To investigate the role of the MuV V protein in viral pathogenesis.
- To generate and characterize a recombinant MuV lacking V protein expression (rMuVΔV).
Main Methods:
- Generated a recombinant MuV (rMuVΔV) from a wild-type US isolate (MuV(Iowa/US/06)).
- Analyzed the impact of V protein deletion on IFN and IL-6 signaling in vitro.
- Assessed the virulence of rMuVΔV in vivo.
Main Results:
- The V protein was confirmed to block IFN and IL-6 signaling.
- rMuVΔV induced significantly higher IL-6 expression in vitro.
- rMuVΔV exhibited marked attenuation in vivo, demonstrating the V protein's essential role in virulence.
Conclusions:
- The MuV V protein is crucial for viral virulence.
- The V protein suppresses IL-6 expression and contributes to pathogenesis.
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