Cytomegalovirus CC chemokine promotes immune cell migration

Jennifer Vomaske, Michael Denton, Craig Kreklywich, Takeshi Andoh, Jessica M. Osborn, Daniel Chen, Ilhem Messaoudi, Susan Orloff, Daniel Streblow

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Cytomegaloviruses manipulate the host chemokine/receptor axis by altering cellular chemokine expression and by encoding multiple chemokines and chemokine receptors. Similar to human cytomegalovirus (HCMV), rat cytomegalovirus (RCMV) encodes multiple CC chemokine-analogous proteins, including r129 (HCMV UL128 homologue) and r131 (HCMV UL130 and MCMV m129/130 homologues). Although these proteins play a role in CMV entry, their function as chemotactic cytokines remains unknown. In the current study, we examined the role of the RCMV chemokine r129 in promoting cellular migration and in accelerating transplant vascular sclerosis (TVS) in our rat heart transplant model. We determined that r129 protein is released into culture supernatants of infected cells and is expressed with late viral gene kinetics during RCMV infection and highly expressed in heart and salivary glands during in vivo rat infections. Using the recombinant r129 protein, we demonstrated that r129 induces migration of lymphocytes isolated from rat peripheral blood, spleen, and bone marrow and from a rat macrophage cell line. Using antibody-mediated cell sorting of rat splenocytes, we demonstrated that r129 induces migration of naïve/central memory CD4+ T cells. Through ligand-binding assays, we determined that r129 binds rat CC chemokine receptors CCR3, CCR4,CCR5, and CCR7. In addition, mutational analyses identified functional domains of r129 resulting in recombinant proteins that fail to induce migration (r129-δNT and -C31A) or alter the chemotactic ability of the chemokine (r129-F43A). Two of the mutant proteins (r129-C31A and -δNT) also act as dominant negatives by inhibiting migration induced by wild-type r129. Furthermore,infection of rat heart transplant recipients with RCMV containing the r129-δNT mutation prevented CMV-induced acceleration of TVS. Together our findings indicate that RCMV r129 is highly chemotactic, which has important implications during RCMV infection and reactivation and acceleration of TVS.

Original languageEnglish (US)
Pages (from-to)11833-11844
Number of pages12
JournalJournal of Virology
Volume86
Issue number21
DOIs
StatePublished - Nov 2012

Fingerprint

Murid herpesvirus 2
Cytomegalovirus
CC Chemokines
Muromegalovirus
cell movement
Cell Movement
chemokines
Chemokines
Human herpesvirus 5
rats
Arteriosclerosis
sclerosis
blood vessels
heart transplant
Transplants
Chemokine Receptors
Cytomegalovirus Infections
Recombinant Proteins
recombinant proteins
CCR Receptors

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Vomaske, J., Denton, M., Kreklywich, C., Andoh, T., Osborn, J. M., Chen, D., ... Streblow, D. (2012). Cytomegalovirus CC chemokine promotes immune cell migration. Journal of Virology, 86(21), 11833-11844. https://doi.org/10.1128/JVI.00452-12

Cytomegalovirus CC chemokine promotes immune cell migration. / Vomaske, Jennifer; Denton, Michael; Kreklywich, Craig; Andoh, Takeshi; Osborn, Jessica M.; Chen, Daniel; Messaoudi, Ilhem; Orloff, Susan; Streblow, Daniel.

In: Journal of Virology, Vol. 86, No. 21, 11.2012, p. 11833-11844.

Research output: Contribution to journalArticle

Vomaske, J, Denton, M, Kreklywich, C, Andoh, T, Osborn, JM, Chen, D, Messaoudi, I, Orloff, S & Streblow, D 2012, 'Cytomegalovirus CC chemokine promotes immune cell migration', Journal of Virology, vol. 86, no. 21, pp. 11833-11844. https://doi.org/10.1128/JVI.00452-12
Vomaske J, Denton M, Kreklywich C, Andoh T, Osborn JM, Chen D et al. Cytomegalovirus CC chemokine promotes immune cell migration. Journal of Virology. 2012 Nov;86(21):11833-11844. https://doi.org/10.1128/JVI.00452-12
Vomaske, Jennifer ; Denton, Michael ; Kreklywich, Craig ; Andoh, Takeshi ; Osborn, Jessica M. ; Chen, Daniel ; Messaoudi, Ilhem ; Orloff, Susan ; Streblow, Daniel. / Cytomegalovirus CC chemokine promotes immune cell migration. In: Journal of Virology. 2012 ; Vol. 86, No. 21. pp. 11833-11844.
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