CMV immune evasion and manipulation of the immune system with aging

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...

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Bibliographic Details
Published in:GeroScience 2017-06, Vol.39 (3), p.273-291
Main Authors: Jackson, Sarah E., Redeker, Anke, Arens, Ramon, van Baarle, Debbie, van den Berg, Sara P. H., Benedict, Chris A., Čičin-Šain, Luka, Hill, Ann B., Wills, Mark R.
Format: Article
Language:English
Subjects:
Aged
Aging
Aging - immunology
Animal models
Animals
Antigens
Biomedical and Life Sciences
CD4 antigen
Cell Biology
Congresses as Topic
Cytomegalovirus
Cytomegalovirus - genetics
Cytomegalovirus - immunology
Cytomegalovirus Infections - genetics
Cytomegalovirus Infections - immunology
Effector cells
Gene expression
Geriatrics/Gerontology
Humans
Immune evasion
Immune Evasion - immunology
Immune response
Immune system
Immunologic Memory - immunology
Immunosuppression
Inoculum
Latency
Latent infection
Life Sciences
Lymphocytes T
Mice
miRNA
Molecular Medicine
Morbidity
Senescence
Vaccines
Virus Latency
Virus Replication
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Summary: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.
ISSN:2509-2715
2509-2723
DOI:10.1007/s11357-017-9986-6