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https://hdl.handle.net/2440/79898
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Type: | Journal article |
Title: | A chemokine-like viral protein enhances alpha interferon production by plasmacytoid dendritic cells but delays CD8⁺ T cell activation and impairs viral clearance |
Other Titles: | A chemokine-like viral protein enhances alpha interferon production by plasmacytoid dendritic cells but delays CD8(+) T cell activation and impairs viral clearance |
Author: | Wikstrom, M. Fleming, P. Comerford, I. McColl, S. Andoniou, C. Degli-Esposti, M. |
Citation: | Journal of Virology, 2013; 87(14):7911-7920 |
Publisher: | Amer Soc Microbiology |
Issue Date: | 2013 |
ISSN: | 0022-538X 1098-5514 |
Statement of Responsibility: | Matthew E. Wikstrom, Peter Fleming, Iain Comerford, Shaun R. McColl, Christopher E. Andoniou, Mariapia A. Degli-Esposti |
Abstract: | Murine 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. |
Keywords: | Spleen Dendritic Cells CD8-Positive T-Lymphocytes Animals Mice, Inbred BALB C Mice Muromegalovirus Interferon-alpha Viral Proteins Chemokines Chemokines, CC Cytokines Fluorescent Antibody Technique Enzyme-Linked Immunosorbent Assay Flow Cytometry Statistics, Nonparametric Lymphocyte Activation Immunity, Innate Adaptive Immunity Immune Evasion |
Rights: | Copyright © 2013, American Society for Microbiology. All Rights Reserved. |
DOI: | 10.1128/JVI.00187-13 |
Published version: | http://dx.doi.org/10.1128/jvi.00187-13 |
Appears in Collections: | Aurora harvest 4 Molecular and Biomedical Science publications |
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