Carroll Feist Endowed Chair of Viral Oncology
Office Phone: 318-675-8332
Laboratory Phone: 318-675-8331
Office Fax: 318-675-5764
Postdoctoral Study, University of North Carolina at Chapel Hill School of Medicine
Ph.D., Immunology - Macrophage Biology, 1990, Virginia Tech
B.S., Biochemistry and Biology, 1985, Virginia Tech
Mechanisms of Human Cytomegalovirus Dissemination and Pathogenesis
(I) We are examining the biological events in human monocytes following HCMV infection because of the critical role these cells play in viral dissemination and the ensuing pathogenesis in AIDS and transplant patients, as well as congenitally infected infants, where HCMV is the leading infectious cause of birth defects. We are addressing from a molecular standpoint, how viral infection of monocytes forces these cells to serve as Trojan Horses for viral spread from the blood into peripheral tissues and then as a source of long-term viral persistence in these tissues. We showed that HCMV specifically activates monocytes and induces monocyte-to-macrophage differentiation and that these viral-induced macrophages become permissive for viral replication, suggesting that HCMV utilizes a novel mechanism for viral dissemination and persistence. Future studies include the examination of the mechanisms responsible for the viral-directed differentiation of monocytes, as well as the functional changes that occur in infected macrophages.
(II) HCMV is also a primary viral candidate in the etiology of atherosclerosis, as evidence links HCMV infection to the development and severity of atherosclerotic disease. The cells associated with disease pathology (endothelial cells, monocytes, and smooth muscle cells) are primary in vivo targets for the virus. Endothelial cells line blood vessels, separating blood from the vessel wall; they provide a non-thrombogenic layer, make key cytokines and growth factors, and are the first cells to be altered/damaged during disease progression. We now have the evidence that direct HCMV infection of endothelial cells induces proliferation, migration, and tubular morphogenesis in the infected endothelial cells, all hallmarks of angiogenesis. Future studies will examine the mechanisms by which HCMV infection of endothelial cells promotes a pro-angiogenic environment.
Collins-McMillen D., J.H. Kim, M.T. Nogalski, E.V. Stevenson, G.C. Chan, J.R. Caskey, S.J. Cieply, A.D. Yurochko. 2016. The role of cellular Bcl-2 in the long-term survival of HCMV-infected monocytes/macrophages. J. Virol. 90:2356-2371. (J. Virol. Spotlight).
Kim, J.H., D. Collins-McMillen, P. Caposio, and A.D. Yurochko. 2016. Viral binding induced signaling drives a unique and extended intracellular trafficking pattern during infection of primary monocytes. Proc. Natl. Acad. Sci. U.S.A. 113:8819-8824.
Campadelli-Fiume, G, D. Collins-McMillen, T. Gianni, and A.D. Yurochko. 2016. Integrins as Herpesviruses’ Receptors and Mediators of the Host Signalosome. Annual Review of Virology. 3:215-236.
Kim, J.H., D. Collins-McMillen, F.D. Goodrum, and A.D. Yurochko. 2017. HCMV requires EGFR and PI(3)K signaling to enter and establish latency in CD34+ human progenitor cells. J. Virol. 91: e01206-16.
Finney, A.C., S.D. Funk, J.M. Green, A. Yurdagul Jr., M.A. Rana, R. Pistorius, M. Henry, A.D. Yurochko, C.B. Patillo, J.G. Traylor, J. Chen, M.D. Woolard, C.G. Kevil, and A.W. Orr. 2017. EphA2 Expression Regulates Inflammation and Fibroproliferative Remodeling in Atherosclerosis. Circulation. 136:566-582.
Yurochko, A.D. 2017. New mechanism by which human cytomegalovirus microRNAs negate the proinflammatory response to infection. mBio. 8:e00505-17.
Collins-McMillen, D., E.V. Stevenson, J.H. Kim, B.-J. Lee, S.J. Cieply, M.T. Nogalski, G.C. Chan, R.W. Frost, III, C.R. Spohn, and A.D. Yurochko. 2017. Human cytomegalovirus utilizes a nontraditional signal transducer and activator of transcription 1 activation cascade via signaling through epidermal growth factor receptor and integrins to efficiently promote the motility, differentiation, and polarization of infected monocytes. J. Virol. 91:e00622-17. (J. Virol. Spotlight).
Crawford, L.B., J.H. Kim, D. Collins-McMillen, B.-J. Lee I. Landais, C. Held, A.D. Yurochko, and P. Caposio. 2018. HCMV encodes a novel FLT3 receptor ligand necessary for hematopoietic cell differentiation and viral reactivation. mBio. Submitted.
All Publications: PubMed