Rat cytomegalovirus-accelerated transplant vascular sclerosis is reduced with mutation of the chemokine-receptor R33

Daniel N. Streblow, Craig N. Kreklywich, Patricia Smith, Jordana L. Soule, Christine Meyer, Michael Yin, Patrick Beisser, Cornelis Vink, Jay A. Nelson, Susan L. Orloff

Research output: Contribution to journalArticle

47 Scopus citations

Abstract

Cytomegalovirus (CMV) infection accelerates transplant vascular sclerosis (TVS) and chronic rejection (CR) in both human and animal solid organ transplantation models. The host/viral mechanisms involved in this process are unclear. We examine the role of the rat CMV (RCMV)-encoded chemokine-receptor R33 in the development of TVS using a rat heart transplantation/CR model. F344 heart grafts were transplanted heterotopically into Lewis recipients. The ability of RCMV lacking the R33 gene (RCMV-Δr33) to accelerate CR/TVS (neointimal index, NI) was compared to wild-type (WT) RCMV. Allograft recipients were infected with 1 × 105 pfu RCMV or RCMV-Δr33 on postoperative day (POD) 1. Grafts from RCWV-Δr33-infected recipients demonstrated an accelerated time to allograft CR compared to grafts from uninfected recipients (POD = 56 vs. 90), this was slower than that seen in grafts from WT-RCMV-infected recipients (POD = 45). Similarly, the degree of graft TVS formation at terminal rejection in RMCV-Δr33 infected recipients was more severe than uninfected recipients (NI = 63 vs. 45), yet not as severe as in WT-RCMV infected recipients (NI = 83). In parallel, RCMV-Δr33 failed to induce vascular smooth muscle cell (SMC) migration in vitro, whereas WT-RCMV induced substantial migration. The RCMV-encoded chemokine-recepfor r33 is critical for RCMV-accelerated TVS/CR and vascular SMC migration.

Original languageEnglish (US)
Pages (from-to)436-442
Number of pages7
JournalAmerican Journal of Transplantation
Volume5
Issue number3
DOIs
StatePublished - Mar 1 2005

Keywords

  • Chemokine receptor
  • Cytomegalovirus
  • Transplant vascular sclerosis (TVS)
  • Transplant vasculopathy

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

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