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

Wikstrom, M.Fleming, P.Comerford, I.McColl, S.Andoniou, C.Degli-Esposti, M.2013-09-112013-09-112013Journal of Virology, 2013; 87(14):7911-79200022-538X1098-5514http://hdl.handle.net/2440/79898Murine 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.enCopyright © 2013, American Society for Microbiology. All Rights Reserved.SpleenDendritic CellsCD8-Positive T-LymphocytesAnimalsMice, Inbred BALB CMiceMuromegalovirusInterferon-alphaViral ProteinsChemokinesChemokines, CCCytokinesFluorescent Antibody TechniqueEnzyme-Linked Immunosorbent AssayFlow CytometryStatistics, NonparametricLymphocyte ActivationImmunity, InnateAdaptive ImmunityImmune EvasionA chemokine-like viral protein enhances alpha interferon production by plasmacytoid dendritic cells but delays CD8⁺ T cell activation and impairs viral clearanceA chemokine-like viral protein enhances alpha interferon production by plasmacytoid dendritic cells but delays CD8(+) T cell activation and impairs viral clearanceJournal article002013097510.1128/JVI.00187-130003210177000132-s2.0-8488030727918503McColl, S. [0000-0003-0949-4660]