Michael Abecassis, MD J Roscoe Miller Distinguished Professor Surgery and Microbiology/Immunology Chief, Division of Organ Transplantation Cytomegalovirus latency and reactivation Curricula: Immunology and Microbial Pathogenesis Molecular Biology and Genetics E-mail:   mabecass@nmh.org

Cytomegalovirus (CMV) is a herpes virus which infects the majority of adults and is able to establish a lifelong latent infection. Reactivation of the virus is frequently observed in transplant recipients, and is associated with serious morbidity and occasionally with mortality. CMV infection can be transmitted from the mother to the fetus during pregnancy and can be associated with severe congenital abnormalities or death of the fetus. Our lab studies the molecular mechanism by which CMV establishes latent infection and reactivates from latency. These studies may suggest strategies for developing drugs which prevent reactivation and its associated sequelae.

Reactivation from latency:
Mice latently infected with murine CMV are used in transplants to investigate the hypothesis that reactivation is triggered by the allogeneic response to the transplanted organ. The inflammatory cytokine TNF and the transcription factor NFkB are particular targets of investigation. Transplanted organs are analyzed for RNA expression and activation of transcription factors known to be involved in regulating viral gene expression. Transgenic and knock-out mice are used to identify cellular genes involved in reactivation of the virus. Gene therapy vectors and pharmacological agents are used to investigate new potential therapeutic agents.

Molecular mechanism of latency:
The mechanism by which CMV is able to hide in a quiescent state in latently infected cells and avoid elimination by the host immune response is unknown. Studies to investigate potential epigenetic mechanisms of transcriptional silencing, including DNA methylation and histone modifications are being explored to investigate viral latency.

Publications:

Kim, et al. (2005) Renal Ischemia/Reperfusion Injury Activates the Enhancer Domain of the Human Cytomegalovirus Major Immediate Early Promoter. American Journal of Transplantation 5 (7), 1606-1613.

Hummel, M. and Abecassis, M. (2002) A model for reactivation of CMV from latency. J. Clin. Virol. 25:S123-S136.

Hummel, M., Zhang, Z., Yan, S., DePlaen, I., Golia, P., Varghese, T.,Thomas, G., and Abecassis, M.I. (2001) Allogeneic transplantation induces expression of cytomegalovirus immediate-early genes in vivo: a model for reactivation from latency. J. Virol. 75:4814-4822.

Koffron AJ, Hummel M, Patterson BK, Yan S, Kaufman DB, Fryer JP, Stuart FP, Abecassis MI. Cellular localization of latent murine cytomegalovirus. J Virology, 72:95-103, 1998.

Abecassis MM, Koffron AJ, Kaplan B, Buckingham M, Muldoon JP, Cribbins AJ, Kaufman DB, Fryer JP, Stuart J, Stuart FP. Role of PCR in the diagnosis and management of CMV in solid organ recipients: what is the predictive value for the development of disease and should PCR be used to guide antiviral therapy? Transplantation, 63:275-9, 1997.

View Publications by Michael Abecassis listed in the National Library of Medicine (PubMed).