title: The non-pathogenic Henipavirus Cedar paramyxovirus phosphoprotein has a compromised ability to target STAT1 and STAT2.
abstract: Immune evasion by the lethal henipaviruses, Hendra (HeV) and Nipah virus, is mediated by its interferon (IFN) antagonist P gene products, phosphoprotein (P), and the related V and W proteins, which can target the signal transducer and activator of transcription 1 (STAT1) and STAT2 proteins to inhibit IFN/STAT signaling. However, it is not clear if the recently identified non-pathogenic Henipavirus, Cedar paramyxovirus (CedPV), is also able to antagonize the STAT proteins. We performed comparative studies between the HeV P gene products (P/V/W) and CedPV-P (CedPV does not encode V or W) and demonstrate that differences exist in their ability to engage the STAT proteins using immunoprecipitation and quantitative confocal microscopic analysis. In contrast to HeV-P gene encoded proteins, the ability of CedPV-P to interact with and relocalize STAT1 or STAT2 is compromised, correlating with a reduced capacity to inhibit the mRNA synthesis of IFN-inducible gene MxA. Furthermore, infection studies with HeV and CedPV demonstrate that HeV is more potent than CedPV in inhibiting the IFN-α-mediated nuclear accumulation of STAT1. These results strongly suggest that the ability of CedPV to counteract the IFN/STAT response is compromised compared to HeV.
authors.affiliation: Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Microbiology, Monash University, Clayton, Victoria, Australia.
authors.forename: Kim G
authors.initials: KG
authors.lastname: Lieu
authors.affiliation: CSIRO Biosecurity Flagship, Australian Animal Health Laboratory, Geelong, Australia.
authors.forename: Glenn A
authors.initials: GA
authors.lastname: Marsh
authors.affiliation: CSIRO Biosecurity Flagship, Australian Animal Health Laboratory, Geelong, Australia; Program in Emerging Infectious Diseases, Duke-NUS Graduate Medical School, Singapore.
authors.forename: Lin-Fa
authors.initials: LF
authors.lastname: Wang
authors.affiliation: Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Microbiology, Monash University, Clayton, Victoria, Australia. Electronic address: hans.netter@monash.edu.
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Netter
mesh_terms: D000595:Amino Acid Sequence; D057809:HEK293 Cells; D006367:HeLa Cells; D045403:Henipavirus / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D045464:Henipavirus Infections / Q000378:metabolism / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000276:immunology / Q000378:metabolism; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000187:drug effects; D060888:Real-Time Polymerase Chain Reaction; D050794:STAT1 Transcription Factor / Q000037:antagonists & inhibitors / Q000378:metabolism*; D050795:STAT2 Transcription Factor / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
chemical_list: D016898:Interferon-alpha; D010750:Phosphoproteins; D012333:RNA, Messenger; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050795:STAT2 Transcription Factor; C494084:STAT2 protein, human; D014764:Viral Proteins
keywords: Cedar virus; Hendra virus; Henipavirus; Innate immunity; Interferon; Pathogenesis; Signal transducers and activators of transcription