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30 - KSHV manipulation of the cell cycle and programmed cell death pathways

from Part II - Basic virology and viral gene effects on host cell functions: gammaherpesviruses

Published online by Cambridge University Press:  24 December 2009

By
Patrick S. Moore
Edited by
Ann Arvin ,
Gabriella Campadelli-Fiume ,
Edward Mocarski ,
Patrick S. Moore ,
Bernard Roizman ,
Richard Whitley  and
Koichi Yamanishi
Patrick S. Moore
Affiliation:
Molecular Virology Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA USA
Ann Arvin
Affiliation:
Stanford University, California
Gabriella Campadelli-Fiume
Affiliation:
Università degli Studi, Bologna, Italy
Edward Mocarski
Affiliation:
Emory University, Atlanta
Patrick S. Moore
Affiliation:
University of Pittsburgh
Bernard Roizman
Affiliation:
University of Chicago
Richard Whitley
Affiliation:
University of Alabama, Birmingham
Koichi Yamanishi
Affiliation:
University of Osaka, Japan
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Summary

Disruptions of cell cycle and apoptotic regulatory control are primary hallmarks tumor cells. It is therefore not surprising that Kaposi's sarcoma-associated herpesvirus (KSHV/HHV8), a tumor virus, encodes viral proteins targeting these cell growth regulation mechanisms. The extent and range of KSHV genes devoted to manipulating these processes is, however, remarkable.

As described in previous chapters, herpesviral structural and replication-related genes are highly conserved among the herpesviruses, including KSHV. In contrast, regulatory genes generating proteins that modify the cellular environment – particularly during latency – are generally unique to each virus. As will become evident in this chapter, even though KSHV and EBV are closely related to each other, there are few sequence homologies among the oncogenes and non-structural regulatory genes found in the two viruses. Despite this, there is a striking functional similarity between the two viruses (Table 30.1). EBV encodes multiple highly evolved transcription factors and signaling proteins that induce many of the same cellular genes that KSHV has pirated into its genome. Further, once herpesvirus targeting of a cellular pathway has been found for one herpesvirus (e.g., HSV-1 downregulation of MHC I surface expression, Hill et al., 1994), searching for functional similarities among other herpesviruses has been particularly rewarding (e.g., Coscoy et al., 2000). It is therefore not surprising that KSHV and EBV share pathways for cell transformation although they achieve this through very different mechanisms.

Type
Chapter
Information
Human Herpesviruses
Biology, Therapy, and Immunoprophylaxis
 , pp. 540 - 558
Publisher: Cambridge University Press
Print publication year: 2007

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