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Rat Cytomegalovirus‐Accelerated Transplant Vascular Sclerosis Is Reduced with Mutation of the Chemokine‐Receptor R33
Author(s) -
Streblow Daniel N.,
Kreklywich Craig N.,
Smith Patricia,
Soule Jordana L.,
Meyer Christine,
Yin Michael,
Beisser Patrick,
Vink Cornelis,
Nelson Jay A.,
Orloff Susan L.
Publication year - 2005
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/j.1600-6143.2004.00711.x
Subject(s) - medicine , chemokine receptor , cytomegalovirus , chemokine , multiple sclerosis , mutation , receptor , immunology , virology , herpesviridae , virus , viral disease , genetics , gene , biology
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 × 10 5 pfu RCMV or RCMV‐Δr33 on postoperative day (POD) 1.Grafts from RCMV‐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‐receptor r33 is critical for RCMV‐accelerated TVS/CR and vascular SMC migration.