A chemokine-like viral protein enhances alpha interferon production by plasmacytoid dendritic cells but delays CD8⁺ T cell activation and impairs viral clearance

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dc.contributor.authorWikstrom, M.
dc.contributor.authorFleming, P.
dc.contributor.authorComerford, I.
dc.contributor.authorMcColl, S.
dc.contributor.authorAndoniou, C.
dc.contributor.authorDegli-Esposti, M.
dc.date.issued2013
dc.description.abstractMurine cytomegalovirus encodes numerous proteins that act on a variety of pathways to modulate the innate and adaptive immune responses. Here, we demonstrate that a chemokine-like protein encoded by murine cytomegalovirus activates the early innate immune response and delays adaptive immunity, thereby impairing viral clearance. The protein, m131/129 (also known as MCK-2), is not required to establish infection in the spleen; however, a mutant virus lacking m131/129 was cleared more rapidly from this organ. In the absence of m131/129 expression, there was enhanced activation of dendritic cells (DC), and virus-specific CD8+ T cells were recruited into the immune response earlier. Viral mutants lacking m131/129 elicited weaker production of alpha interferon (IFN-α) at 40 h postinfection, indicating that this protein exerts its effects during early rounds of viral replication in the spleen. Furthermore, while wild-type and mutant viruses activated plasmacytoid dendritic cells (pDC) equally at this time, as measured by the upregulation of costimulatory molecules, the presence of m131/129 stimulated more pDC to secrete IFN-α, accounting for the stronger IFN-α response than from the wild-type virus. These data provide evidence for a novel immunomodulatory function of a viral chemokine and expose the multifunctionality of immune evasion proteins. In addition, these results broaden our understanding of the interplay between innate and adaptive immunity.
dc.description.statementofresponsibilityMatthew E. Wikstrom, Peter Fleming, Iain Comerford, Shaun R. McColl, Christopher E. Andoniou, Mariapia A. Degli-Esposti
dc.identifier.citationJournal of Virology, 2013; 87(14):7911-7920
dc.identifier.doi10.1128/JVI.00187-13
dc.identifier.issn0022-538X
dc.identifier.issn1098-5514
dc.identifier.orcidMcColl, S. [0000-0003-0949-4660]
dc.identifier.urihttp://hdl.handle.net/2440/79898
dc.language.isoen
dc.publisherAmer Soc Microbiology
dc.rightsCopyright © 2013, American Society for Microbiology. All Rights Reserved.
dc.source.urihttps://doi.org/10.1128/jvi.00187-13
dc.subjectSpleen
dc.subjectDendritic Cells
dc.subjectCD8-Positive T-Lymphocytes
dc.subjectAnimals
dc.subjectMice, Inbred BALB C
dc.subjectMice
dc.subjectMuromegalovirus
dc.subjectInterferon-alpha
dc.subjectViral Proteins
dc.subjectChemokines
dc.subjectChemokines, CC
dc.subjectCytokines
dc.subjectFluorescent Antibody Technique
dc.subjectEnzyme-Linked Immunosorbent Assay
dc.subjectFlow Cytometry
dc.subjectStatistics, Nonparametric
dc.subjectLymphocyte Activation
dc.subjectImmunity, Innate
dc.subjectAdaptive Immunity
dc.subjectImmune Evasion
dc.titleA chemokine-like viral protein enhances alpha interferon production by plasmacytoid dendritic cells but delays CD8⁺ T cell activation and impairs viral clearance
dc.title.alternativeA chemokine-like viral protein enhances alpha interferon production by plasmacytoid dendritic cells but delays CD8(+) T cell activation and impairs viral clearance
dc.typeJournal article
pubs.publication-statusPublished

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