Rinderpest virus blocks type I and type II interferon action: role of structural and nonstructural proteins.
Rinderpest virus (RPV) is a paramyxovirus closely related to the human pathogen Measles virus. It causes severe disease in cattle, buffalo, and some wild animals; although it can infect humans, it does not cause disease. Here, we demonstrate that RPV blocks the action of both type I (alpha) and type II (gamma) interferons (IFNs) by blocking the phosphorylation and nuclear translocation of STAT1 and STAT2 and that this block is not related to species specificity. In addition, both wild-type virulent and vaccine strains of the virus blocked IFN action. Unlike the case with some other paramyxoviruses, neither STAT1 nor STAT2 is degraded upon virus infection. STAT1 is bound by both the viral structural protein P, and thereby recruited to concentrations of viral protein in the cell, and the nonstructural protein V. Although both P and V proteins bind to STAT1 and can block IFN action when expressed in transfected cells, the IFN antagonist activity of the P protein is weaker than that of the V protein. The viral C protein also seems to weakly block IFN-induced activation of STAT1 in transfection experiments. However, studies with knockout viruses showed that the viral V protein appears to be the dominant inhibitor of IFN signaling in the context of virus infection, since prevention of viral V expression restored the IFN sensitivity of infected cells. Although a change in the distribution pattern of STAT2 was observed in virus-infected cells, STAT2 was not bound by any viral protein.
Nanda
Sambit K
SK
Institute for Animal Health, Ash Road, Pirbright, Surrey GU24 0NF, United Kingdom.
Baron
Michael D
MD
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002417:Cattle; D002467:Cell Nucleus; D002522:Chlorocebus aethiops; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000378:metabolism / Q000821:virology; D010766:Phosphorylation; D021381:Protein Transport; D012302:Rinderpest virus / Q000502:physiology*; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D012867:Skin / Q000166:cytology / Q000378:metabolism / Q000821:virology; D014709:Vero Cells / Q000378:metabolism / Q000821:virology; D017361:Viral Nonstructural Proteins / Q000502:physiology*; D015678:Viral Structural Proteins / Q000502:physiology*; D014779:Virus Replication
D000998:Antiviral Agents; D016898:Interferon-alpha; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D017361:Viral Nonstructural Proteins; D015678:Viral Structural Proteins; D007371:Interferon-gamma