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The Anti-apoptotic Murine Cytomegalovirus Protein vMIA-m38.5 Induces Mast Cell Degranulation.


ABSTRACT: Mast cells (MC) represent "inbetweeners" of the immune system in that they are part of innate immunity by acting as first-line sentinels for environmental antigens but also provide a link to adaptive immunity by secretion of chemokines that recruit CD8 T cells to organ sites of infection. An interrelationship between MC and cytomegalovirus (CMV) has been a blank area in science until recently when the murine model revealed a role for MC in the resolution of pulmonary infection by murine CMV (mCMV). As to the mechanism, MC were identified as a target cell type of mCMV. Infected MC degranulate and synthesize the CC-chemokine ligand-5 (CCL-5), which is released to attract protective virus-specific CD8 T cells to infected host tissue for confining and eventually resolving the productive, cytopathogenic infection. In a step forward in our understanding of how mCMV infection of MC triggers their degranulation, we document here a critical role for the mCMV m38.5 gene product, a mitochondria-localized inhibitor of apoptosis (vMIA). We show an involvement of mCMV vMIA-m38.5 in MC degranulation by two reciprocal approaches: first, by enhanced degranulation after m38.5 gene transfection of bone marrow-derived cell culture-grown MC (BMMC) and, second, by reduced degranulation of MC in peritoneal exudate cell populations infected ex corpore or in corpore with mutant virus mCMV-?m38.5. These studies thus reveal a so far unknown function of mCMV vMIA-m38.5 and offer a previously unconsidered but biologically relevant cell system for further analyzing functional analogies between vMIAs of different CMV species.

SUBMITTER: Schmiedeke JK 

PROVIDER: S-EPMC7477074 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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The Anti-apoptotic Murine Cytomegalovirus Protein vMIA-m38.5 Induces Mast Cell Degranulation.

Schmiedeke Julia K JK   Hartmann Ann-Kathrin AK   Ruckenbrod Teresa T   Stassen Michael M   Reddehase Matthias J MJ   Lemmermann Niels A NA  

Frontiers in cellular and infection microbiology 20200825


Mast cells (MC) represent "inbetweeners" of the immune system in that they are part of innate immunity by acting as first-line sentinels for environmental antigens but also provide a link to adaptive immunity by secretion of chemokines that recruit CD8 T cells to organ sites of infection. An interrelationship between MC and cytomegalovirus (CMV) has been a blank area in science until recently when the murine model revealed a role for MC in the resolution of pulmonary infection by murine CMV (mCM  ...[more]

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