CMV immune evasion and manipulation of the immune system with aging

Sarah E. Jackson, Anke Redeker, Ramon Arens, Debbie van Baarle, Sara P.H. van Den Berg, Chris A. Benedict, Luka Čičin-Šain, Ann Hill, Mark R. Wills

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Human cytomegalovirus (HCMV) encodes numerous proteins and microRNAs that function to evade the immune response and allow the virus to replicate and disseminate in the face of a competent innate and acquired immune system. The establishment of a latent infection by CMV, which if completely quiescent at the level of viral gene expression would represent an ultimate in immune evasion strategies, is not sufficient for lifelong persistence and dissemination of the virus. CMV needs to reactivate and replicate in a lytic cycle of infection in order to disseminate further, which occurs in the face of a fully primed secondary immune response. Without reactivation, latency itself would be redundant for the virus. It is also becoming clear that latency is not a totally quiescent state, but is characterized by limited viral gene expression. Therefore, the virus also needs immune evasion strategies during latency. An effective immune response to CMV is required or viral replication will cause morbidity and ultimately mortality in the host. There is clearly a complex balance between virus immune evasion and host immune recognition over a lifetime. This poses the important question of whether long-term evasion or manipulation of the immune response driven by CMV is detrimental to health. In this meeting report, three groups used the murine model of CMV (MCMV) to examine if the contribution of the virus to immune senescence is set by the (i) initial viral inoculum, (ii) inflation of T cell responses, (iii) or the balance between functionally distinct effector CD4+ T cells. The work of other groups studying the CMV response in humans is discussed. Their work asks whether the ability to make immune responses to new antigens is compromised by (i) age and HCMV carriage, (ii) long-term exposure to HCMV giving rise to an overall immunosuppressive environment and increased levels of latent virus, or (iii) adapted virus mutants (used as potential vaccines) that have the capacity to elicit conventional and unconventional T cell responses.

Original languageEnglish (US)
Pages (from-to)1-19
Number of pages19
JournalGeroScience
DOIs
StateAccepted/In press - Jun 24 2017

Fingerprint

Immune Evasion
Immune System
Viruses
Cytomegalovirus
Viral Genes
T-Lymphocytes
Gene Expression
Economic Inflation
Immunosuppressive Agents
Infection
MicroRNAs
Vaccines
Morbidity
Antigens
Mortality
Health

Keywords

  • Aging
  • Cytomegalovirus
  • Immune evasion
  • Immune manipulation

ASJC Scopus subject areas

  • Aging
  • Geriatrics and Gerontology

Cite this

Jackson, S. E., Redeker, A., Arens, R., van Baarle, D., van Den Berg, S. P. H., Benedict, C. A., ... Wills, M. R. (Accepted/In press). CMV immune evasion and manipulation of the immune system with aging. GeroScience, 1-19. https://doi.org/10.1007/s11357-017-9986-6

CMV immune evasion and manipulation of the immune system with aging. / Jackson, Sarah E.; Redeker, Anke; Arens, Ramon; van Baarle, Debbie; van Den Berg, Sara P.H.; Benedict, Chris A.; Čičin-Šain, Luka; Hill, Ann; Wills, Mark R.

In: GeroScience, 24.06.2017, p. 1-19.

Research output: Contribution to journalArticle

Jackson, SE, Redeker, A, Arens, R, van Baarle, D, van Den Berg, SPH, Benedict, CA, Čičin-Šain, L, Hill, A & Wills, MR 2017, 'CMV immune evasion and manipulation of the immune system with aging', GeroScience, pp. 1-19. https://doi.org/10.1007/s11357-017-9986-6
Jackson SE, Redeker A, Arens R, van Baarle D, van Den Berg SPH, Benedict CA et al. CMV immune evasion and manipulation of the immune system with aging. GeroScience. 2017 Jun 24;1-19. https://doi.org/10.1007/s11357-017-9986-6
Jackson, Sarah E. ; Redeker, Anke ; Arens, Ramon ; van Baarle, Debbie ; van Den Berg, Sara P.H. ; Benedict, Chris A. ; Čičin-Šain, Luka ; Hill, Ann ; Wills, Mark R. / CMV immune evasion and manipulation of the immune system with aging. In: GeroScience. 2017 ; pp. 1-19.
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