Antiviral therapy can reverse the development of immune senescence in elderly mice with latent cytomegalovirus infection

Beswick, Mark (2013). Antiviral therapy can reverse the development of immune senescence in elderly mice with latent cytomegalovirus infection. University of Birmingham. Ph.D.

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Abstract

Immune responses towards Cytomegalovirus (CMV) often increase in magnitude with age; a phenomenon termed ‘memory inflation’. Elevated CMV-specific immunity is correlated with an increased mortality rate in elderly individuals and there is considerable interest in therapeutic approaches that may reverse this. Latent CMV infection is characterised by intermittent episodes of subclinical viral reactivation which may play a role in boosting CMV- specific immunity however, the relative importance of reactivation in the development of "memory inflation" is currently uncertain. In order to investigate these questions valaciclovir was administered as to aged mice with established murine CMV (MCMV) infection to block stochastic lytic reactivation from latency. Following 12 months of treatment there were highly significant reductions in the frequency of the MCMV-specific CD8\(^+\) T-lymphocytes and the residual MCMV-tetramer specific response exhibited a less differentiated phenotype. The accumulation of memory cells associated with untreated MCMV infection suppressed the proportion of naïve CD8\(^+\) T-cells by 60%, whereas antiviral treatment was able to completely restore this effect. Furthermore, valaciclovir treatment of MCMV reduced the elevated viral load that followed influenza virus challenge demonstrating that anti-MCMV treatment can lead to improved immunity to other pathogens in old age.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

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