Faculty Collaboration Database

Murine cytomegalovirus immediate-early 1 gene expression correlates with increased GVHD after allogeneic hematopoietic cell transplantation in recipients reactivating from latent infection. PLoS One 2013;8(4):e61841

Date

04/19/2013

Pubmed ID

23596528

Pubmed Central ID

PMC3626592

DOI

10.1371/journal.pone.0061841

Scopus ID

2-s2.0-84876195809 (requires institutional sign-in at Scopus site)   11 Citations

Abstract

The success of allogeneic (allo) hematopoietic cell transplantation (HCT) is limited by its treatment related complications, mostly graft versus host disease (GVHD) and fungal and viral infections. CMV reactivation after HCT has been associated with increased morbidity and mortality, and a causal relation between GVHD, immunosuppressive therapy and vice versa has been postulated. Using a low GVHD severity murine HCT model, we assessed the role of MCMV reactivation and GVHD development. BALB/c mice were infected with either murine CMV (MCMV) or mock and monitored for 25 weeks to establish latency, followed by sublethal irradiation conditioning and infusion of bone marrow plus splenocytes from either syngeneic (syn) BALB/c or allo B10.D2 donors. Engraftment of allo donor cells was confirmed by PCR for D2Mit265 gene product size. Day+100 mortality and overall GVHD severity in allo MCMV pre-infected recipients was higher than in allo mock controls. Pathologic changes of lung and liver GVHD in immediate-early gene 1 (IE1) positive recipients were significantly increased compared to mock controls, and were only slightly increased in IE1 negative. No significant gut injury was seen in any group. Aggravated lung injury in IE1 positive recipients correlated with higher BAL cell counts both for total cells and for CD4+ T cells when compared with mock controls, and also with protein expression of lung IFN-gamma and liver TNF. No evidence for CMV specific morphologic changes was seen on histopathology in any organ of IE1 positive recipients, suggesting that CMV reactivation is related to increased GVHD severity but does not require active CMV disease, strengthening the concept of a reciprocal relationship between CMV and GVHD.

Author List

Palaniyandi S, Radhakrishnan SV, Karlsson FJ, Stokes KY, Kittan N, Huber E, Hildebrandt GC

Author

Sabarinath Venniyil Radhakrishnan MD Assistant Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Antibodies, Viral
Chemokines
Chimerism
Female
Gene Expression
Genes, Immediate-Early
Graft vs Host Disease
Hematopoietic Stem Cell Transplantation
Herpesviridae Infections
Immunoglobulin G
Inflammation
Liver
Lung
Mice
Muromegalovirus
Polymorphism, Genetic
Transplantation, Homologous
Virus Activation
Virus Latency