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Article

Platelet-endothelial associations may promote cytomegalovirus replication in the salivary gland in mice

ORCID Icon, , , , , , , , , , , , , , & show all
Pages 860-868 | Received 13 Sep 2019, Accepted 31 Oct 2019, Published online: 14 Nov 2019
 

Abstract

Platelet decline is a feature of many acute viral infections, including cytomegalovirus (CMV) infection in humans and mice. Platelet sequestration in association with other cells, including endothelium and circulating leukocytes, can contribute to this decline and influence the immune response to and pathogenesis of viral infection. We sought to determine if platelet-endothelial associations (PEAs) contribute to platelet decline during acute murine CMV (mCMV) infection, and if these associations affect viral load and production. Male BALB/c mice were infected with mCMV (Smith strain), euthanized at timepoints throughout acute infection and compared to uninfected controls. An increase in PEA formation was confirmed in the salivary gland at all post-inoculation timepoints using immunohistochemistry for CD41+ platelets co-localizing with CD34+ vessels. Platelet depletion did not change amount of viral DNA or timecourse of infection, as measured by qPCR. However, platelet depletion reduced viral titer of mCMV in the salivary glands while undepleted controls demonstrated robust replication in the tissue by plaque assay. Thus, platelet associations with endothelium may enhance the ability of mCMV to replicate within the salivary gland. Further work is needed to determine the mechanisms behind this effect and if pharmacologic inhibition of PEAs may reduce CMV production in acutely infected patients.

Acknowledgements

Victoria Baxter, Elizabeth Engle, Erin Shirk, Samuel Brill, Andrew Johanson and Megan McCarron for advice in assay development. Suzanne Queen, Brandon Bullock and Ming Li for management of shared lab areas, and Sarah Beck, Janice Clements, and Joseph Mankowski for use of shared lab equipment.

Author Contributions

Conceptualization, K.M.N., R.B. and K.A.M.P.; Data curation, A.M.B., A.L.C. and C.E.L.; Formal analysis, A.M.B. and K.A.M.P.; Funding acquisition, R.A.B. and K.A.M.P.; Investigation, A.M.B., A.L.C., K.M.N., J.K.B., K.T.J., C.E.L., B.D., C.G.C., S.V., G.C., S.M.G.M., K.M. and S.A.A.; Methodology, A.L.C., K.M.N., J.K.B, K.T.J., C.E.L., Y.P.S. and R.A.B.; Project administration, K.A.M.P.; Resources, Y.P.S. and R.A.B.; Supervision, A.M.B., C.E.L, and K.A.M.P.; Visualization, A.M.B.; Writing – original draft, A.M.B. and K.A.M.P.; Writing – review & editing, A.M.B, R.A.B. and K.A.M.P.

Disclosures

The authors declare no conflict of interest.

Supplementary material

Supplementary data for this article can be accessed here.

Additional information

Funding

This work was supported by NIH under P30 MH075673 and a Johns Hopkins University STAR award, and salary support from NIH under T32 OD011089 (A. Braxton), Johns Hopkins University STAR award (A. Chalmin), Merial Veterinary Scholars Program (J. Brockhurst), Johns Hopkins University PURA award (K. Johnson), NIH under R01DC013550 (R. Arav-Boger), NIH under 1R01AI093701 (R. Arav-Boger), and NIH under K01 OD018244 (K. Metcalf Pate);National Institutes of Health [1R01AI093701,K01 OD018244,P30 MH075673,R01DC013550,T32 OD011089].

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