Philip E. Pellett

Home

Welcome!

Research

Directory

Alumni

	Philip E Pellett, PhD
	Professor
	6225 Scott Hall
	313-577-6494
	ppellett@med.wayne.edu

Dr. Pellett’s research is aimed at understanding the biology of human herpesviruses and improving clinical outcomes of herpesvirus infections. Dr. Pellett earned his Ph.D. in the laboratory of Dr. Bernard Roizman at the University of Chicago in 1986. He served as Chief of the Herpesvirus Section at the US Centers for Disease Control and Prevention from 1986 until 2003, and was Director of Herpesvirus Translational and Basic Research at the Cleveland Clinic prior to joining Wayne State University in 2007.

Herpesviruses: Molecular Marvels and Potent Pathogens

Of the human herpesviruses, human cytomegalovirus (HCMV) has the greatest clinical impact. It is a leading cause of congenitally acquired mental retardation and deafness, is a major pathogen in immunocompromised patients, and may contribute to the development of atherosclerosis and other inflammation-linked vascular diseases. We are engaged in basic studies of the molecular and cellular biology of HCMV, as well as in clinically oriented translational research.

HCMV Molecular and Cellular Biology

Cell biology of HCMV virion assembly. Human cytomegalovirus induces profound changes in infected-cell morphology, including formation of large cytoplasmic inclusions that correspond to the virion assembly complex (AC). We found that the AC is arranged such that Golgi- and trans-Golgi-derived vesicles are at the outer periphery of the AC and early endosome-derived vesicles are at its center. This counterintuitive arrangement nonetheless allows for a conventional order of membrane-protein biosynthesis and transport. The resulting model of AC structure suggests a mechanism by which the virus can regulate the order of tegument assembly. We are working to identify the viral proteins responsible for orchestrating the dramatic cellular remodeling and to learn how the AC works.

HCMV and cellular microRNAs. The human genome encodes approximately 500 microRNAs (miRNAs) that individually and collectively regulate many important cellular processes, such as development. We found that HCMV infection alters expression of cellular microRNA species that affect its replication, and have identified some of the cellular genes affected by the virally-regulated miRNAs. We are working to define the roles of miRNAs in HCMV biology.

HCMV gene function. In spite of intense effort, the functions of most of the >165 genes encoded by HCMV remain unknown, a significant barrier to the rational design of improved tools for preventing and treating HCMV infections. The HCMV US12 gene family is a family of ten viral genes that have sequence properties in common with G protein-coupled receptors. We have found that one of them is expressed in a segmented manner, with a portion transiting the nucleus during the course of infection, possibly playing a role in rearranging the cytoplasm to better accommodate virus assembly. We are studying the biological properties of these proteins and their roles in infection.

Translational Research

The Translational Research component of our program involves multidisciplinary collaboration between basic laboratory scientists, clinical virologists, immunologists, infectious disease specialists, epidemiologists, and biostatisticians. We are examining the pathogenic role of herpesviruses in immunocompromised patients, and are developing new methods for diagnosing and treating herpesvirus infections.

**Selected Publications**
Das, S. and P.E. Pellett. 2011. Spatial relationships between markers for secretory and endosomal machinery in human cytomegalovirus-infected cells versus those in uninfected cells. J. Virol. 85:5864-5879.
Dhuruvasan, K, G. Sivasubramanian, and P.E. Pellett. 2011. Roles of host and viral microRNAs in human cytomegalovirus biology. Virus Res. 157:180-192.
Wang, F.Z., F. Weber, C. Croce, C.-G. Liu, X. Liao, and P.E. Pellett. 2008. Human cytomegalovirus infection alters expression of cellular microRNA species that affect its replication. J. Virol. 82:9065-9074. J. Virol. Spotlight article (82:8955) and ASM Microbe Journal Highlights (3:530).
Das, S., A. Vasanji, and P.E. Pellett. 2007. Three dimensional structure of the human cytomegalovirus cytoplasmic virion assembly complex includes a reoriented secretory apparatus. J. Virol. 81:11861-11869.
Pellett, P.E. and J. Goldfarb. 2007. Multilane highway to congenital infection. J. Infect. Dis. 196:1276-1278.
Das, S. and P.E. Pellett. 2007. Members of the HCMV US12 family of predicted heptaspanning membrane proteins have unique intracellular distributions, including association with the cytoplasmic virion assembly complex. Virology 361:263-273.
Pellett, P.E. and B. Roizman. 2007. The Herpesviridae: a brief introduction. In Fields Virology, 5^th ed., Knipe et al., eds., Lippincott, Williams, & Wilkins, Philadelphia, Vol. 2, Chapt. 66: 2479-2499.
Hladik, W., S.C. Dollard, J. Mermin, A. L. Fowlkes, R. Downing, M. M. Amin, F. Banage, E. Nzaro, P. Kataaha, T.J. Dondero, P.E. Pellett, E.M. Lackritz. 2006. Transmission of human herpesvirus 8 by blood transfusion. New England J. Med., 355:1331-1338.
Lesniewski, M., S. Das, Y. Skomorovska-Prokvolit, F.-Z. Wang, and P.E. Pellett. 2006. Primate cytomegalovirus US12 gene family: a distinct and diverse clade of seven-transmembrane proteins. Virology 354:286-298.
Das, S., Y. Skomorovska-Prokvolit, F.-Z. Wang, and P.E. Pellett. 2006. Infection-dependent nuclear localization of US17, a member of the US12 family of human cytomegalovirus-encoded seven-transmembrane proteins. J. Virol. 80:1191-1203.