The Contribution of Cytomegalovirus Infection to Immune Senescence Is Set by the Infectious Dose.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Remmerswaal, Ester B M
van der Gracht, Esmé T I
Welten, Suzanne P M
Ten Berge, Ineke J M
van Lier, René A W
van Unen, Vincent
MetadataShow full item record
AbstractThe relationship between human cytomegalovirus (HCMV) infections and accelerated immune senescence is controversial. Whereas some studies reported a CMV-associated impaired capacity to control heterologous infections at old age, other studies could not confirm this. We hypothesized that these discrepancies might relate to the variability in the infectious dose of CMV occurring in real life. Here, we investigated the influence of persistent CMV infection on immune perturbations and specifically addressed the role of the infectious dose on the contribution of CMV to accelerated immune senescence. We show in experimental mouse models that the degree of mouse CMV (MCMV)-specific memory CD8+ T cell accumulation and the phenotypic T cell profile are directly influenced by the infectious dose, and data on HCMV-specific T cells indicate a similar connection. Detailed cluster analysis of the memory CD8+ T cell development showed that high-dose infection causes a differentiation pathway that progresses faster throughout the life span of the host, suggesting a virus-host balance that is influenced by aging and infectious dose. Importantly, short-term MCMV infection in adult mice is not disadvantageous for heterologous superinfection with lymphocytic choriomeningitis virus (LCMV). However, following long-term CMV infection the strength of the CD8+ T cell immunity to LCMV superinfection was affected by the initial CMV infectious dose, wherein a high infectious dose was found to be a prerequisite for impaired heterologous immunity. Altogether our results underscore the importance of stratification based on the size and differentiation of the CMV-specific memory T cell pools for the impact on immune senescence, and indicate that reduction of the latent/lytic viral load can be beneficial to diminish CMV-associated immune senescence.
CitationThe Contribution of Cytomegalovirus Infection to Immune Senescence Is Set by the Infectious Dose. 2017, 8:1953 Front Immunol
AffiliationHelmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany.
JournalFrontiers in immunology
The following license files are associated with this item:
- Creative Commons
Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by-nc-sa/4.0/
- Immune senescence: relative contributions of age and cytomegalovirus infection.
- Authors: Mekker A, Tchang VS, Haeberli L, Oxenius A, Trkola A, Karrer U
- Issue date: 2012
- An attenuated temperature-sensitive strain of cytomegalovirus (tsm5) establishes immunity without development of CD8(+) T cell memory inflation.
- Authors: Beswick M, Pachnio A, Al-Ali A, Sweet C, Moss PA
- Issue date: 2013 Nov
- Antiviral therapy can reverse the development of immune senescence in elderly mice with latent cytomegalovirus infection.
- Authors: Beswick M, Pachnio A, Lauder SN, Sweet C, Moss PA
- Issue date: 2013 Jan
- Gammaherpesvirus latency differentially impacts the generation of primary versus secondary memory CD8+ T cells during subsequent infection.
- Authors: Barton ES, Rajkarnikar S, Langston PK, Price MJ, Grayson JM
- Issue date: 2014 Nov
- Cytomegalovirus-specific T cell immunity is maintained in immunosenescent rhesus macaques.
- Authors: Cicin-Sain L, Sylwester AW, Hagen SI, Siess DC, Currier N, Legasse AW, Fischer MB, Koudelka CW, Axthelm MK, Nikolich-Zugich J, Picker LJ
- Issue date: 2011 Aug 15