Aspects of Human Cytomegalovirus Latency and Reactivation - Human Cytomegalovirus - page 289

Aspects of Human Cytomegalovirus
Latency and Reactivation
M. Reeves , J. Sinclair ( ü )
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 298
Latency, Carriage and Reactivation of HCMV in the Cells of the Myeloid Lineage . . . . . . . 298
Models of HCMV Latency Using Experimental Infection . . . . . . . . . . . . . . . . . . . . . . . . . . . 300
Viral Gene Expression Associated with HCMV Latency . . . . . . . . . . . . . . . . . . . . . . . . . . . . 301
Key Aspects of HCMV Latency and Reactivation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 302
The Establishment of HCMV Latency. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 302
The Maintenance of HCMV Latency. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 304
Reactivation of HCMV from Latency . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 305
Other Sites of HCMV Latency . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 308
Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 309
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 309
Abstract Primary infection of healthy individuals with human cytomegalovirus
(HCMV) is usually asymptomatic and results in the establishment of a lifelong
latent infection of the host. Although no overt HCMV disease is observed in healthy
carriers, due to effective immune control, severe clinical symptoms associated with
HCMV reactivation are observed in immunocompromised transplant patients and
HIV sufferers. Work from a number of laboratories has identified the myeloid lineage
as one important site for HCMV latency and reactivation and thus has been the
subject of extensive study. Attempts to elucidate the mechanisms controlling viral
latency have shown that cellular transcription factors and histone proteins influence
HCMV gene expression profoundly and that the type of cellular environment virus
encounters upon infection may have a critical role in determining a lytic or latent
infection and subsequent reactivation from latency. Furthermore, the identification
of a number of viral gene products expressed during latent infection suggests a
more active role for HCMV during latency. Defining the role of these viral proteins
in latently infected cells will be important for our full understanding of HCMV
latency and reactivation in vivo.
J. Sinclair
Department of Medicine , University of Cambridge, Addenbrooke's Hospital Cambridge,
CB2 2QQ , UK
[e-mail]