Cytomegalovirus latency

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

The strategies of human cytomegalovirus (HCMV) to establish latency with the capability of reactivation include viral latency in certain undifferentiated cells, followed by reactivation of the virus upon differentiation of the same cells, escape from recognition by the immune system, and resistance to apoptosis of the latently infected cells. Bone marrow-derived cells of the myeloid lineage, CD34+ and CD33+ progenitors, and CD14+ monocytes are the major natural sites of HCMV latency. The latent HCMV is reactivated and exhibits productive replication in the terminally differentiated macrophages and dendritic cells. Model systems have been established for the investigation of the differentiation-dependent replication. The HCMV major immediate-early (MIE) gene is not transcribed in undifferentiated NTera-2 embryonal carcinoma (EC) cells, but it is transcribed in their differentiated derivatives, offering an in vitro model with which to study the developmental regulation of the activity of a viral gene during the differentiation of these cells. After natural or experimental infection, latency-associated transcripts are present in a few of the cells of the myeloid lineage, but their role in the development and maintenance of latency, or in viral reactivation, is not clear. The molecular mechanisms involved in the blockade of the MIE gene expression in undifferentiated cells include covalent closure of the circular conformation of the viral genome, silencing of the viral MIE promoter (MIEP) by histone deacetylation, and increases in the expression of negatively regulating transcription factors responsible for the recruitment of histone deacetylases around the MIEP. In HCMV-infected differentiated NTera2 cells, and in the terminally differentiated cells of the myeloid lineage, the MIEP becomes associated with hyperacetylated histones; this results in an open structure of chromatin, enhancing the access of DNA-binding factors that positively regulate MIE gene expression and viral replication. These model systems contribute to an understanding of HCMV latency and reactivation in vivo. Further strategies whereby HCMV establishes lifelong latency in the host include the development of mechanisms for surviving against the primed immune system. In this fight, the virus has evolved gene products to avoid immune surveillance. Encoded in the US region of the HCMV genome, five glycoproteins impede the MHC class I presentation pathway by independent mechanisms. Moreover, some of these and others can block MHC class II presentation of the viral antigens to CD4+ T cells. Decrease in the MHC class I molecules on the cell surface results in the susceptibility of infected cells to attack by natural killer (NK) cells. It is not surprising, however, that HCMV has also evolved strategies to escape NK cell immune surveillance.

Original languageEnglish
Title of host publicationLatency Strategies of Herpesviruses
PublisherSpringer US
Pages55-85
Number of pages31
ISBN (Print)9780387341279, 038732464X, 9780387324647
DOIs
Publication statusPublished - 2007

Fingerprint

Cytomegalovirus
Immediate-Early Genes
Cell Lineage
Natural Killer Cells
Histones
Cell Differentiation
Immune System
Virus Latency
Viruses
Embryonal Carcinoma Stem Cells
Gene Expression
Histone Deacetylases
Viral Genes
Viral Antigens
Viral Genome
Human Genome
Bone Marrow Cells
Dendritic Cells
Chromatin
Monocytes

ASJC Scopus subject areas

  • Medicine(all)
  • Immunology and Microbiology(all)

Cite this

Burián, K., & Gönczöl, E. (2007). Cytomegalovirus latency. In Latency Strategies of Herpesviruses (pp. 55-85). Springer US. https://doi.org/10.1007/978-0-387-34127-9-3

Cytomegalovirus latency. / Burián, K.; Gönczöl, E.

Latency Strategies of Herpesviruses. Springer US, 2007. p. 55-85.

Research output: Chapter in Book/Report/Conference proceedingChapter

Burián, K & Gönczöl, E 2007, Cytomegalovirus latency. in Latency Strategies of Herpesviruses. Springer US, pp. 55-85. https://doi.org/10.1007/978-0-387-34127-9-3
Burián K, Gönczöl E. Cytomegalovirus latency. In Latency Strategies of Herpesviruses. Springer US. 2007. p. 55-85 https://doi.org/10.1007/978-0-387-34127-9-3
Burián, K. ; Gönczöl, E. / Cytomegalovirus latency. Latency Strategies of Herpesviruses. Springer US, 2007. pp. 55-85
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