Recent advances in CMV tropism, latency, and diagnosis during aging

Abstract

Human cytomegalovirus (CMV) is one of the largest viruses known to cause human diseases. Chronic CMV infection, as defined by anti-CMV IgG serology, increases with age and is highly prevalent in older adults. It has complex biology with significant immunologic and health consequences. This article aims to summarize research findings presented at the 6th International Workshop on CMV and Immunosenescence that relate to advances in the areas of CMV tropism, latency, CMV manipulation of cell metabolism, and T cell memory inflation, as well as novel diagnostic evaluation and translational research of chronic CMV infection in older adults. Information summarized here represents the current state of knowledge in these important fields. Investigators have also identified a number of areas that deserve further and more in-depth investigation, including building more precise parallels between mouse CMV (mCMV) and human CMV (HCMV) research. It is hoped that this article will also stimulate engaging discussion on strategies and direction to advance the science to the next level.

The (gradual) rise of memory inflation

“…The accumulation of these with time is not so evident within an individual; although, they do appear to accumulate with age looking at populations cross‐sectionally. Thus, although they are by no means identical, the word “inflationary” has also been used to describe immune responses to HCMV, even though these are much more complex and diverse 14, 18, 19, 20. This is reasonable, given the very distinct features of both the mouse and human response, which overlap in many ways—but it depends on what is meant by memory “inflation” hence the attempt at a definition below.…”

“…This has been reviewed elsewhere and chiefly in the context of the role of CMV 20. There is quite conflicting evidence of the impact of CMV although newer data focusing on subsets of CMV‐seropositive aged populations who have poor control over the virus provide a more convincing association between infection and clinical outcomes 14, 90, 91.…”

“…89 This has been reviewed elsewhere and chiefly in the context of the role of CMV. 20 There is quite conflicting evidence of the impact of CMV although newer data focusing on subsets of CMV-seropositive aged populations who have poor control over the virus provide a more convincing association between infection and clinical outcomes. 14,90,91 Since at a minimum, memory inflation is driven by antigen, a loss of control over virus (as evidenced, for example indirectly via higher IgG levels or directly by detection in monocytes or in urine) should be manifest as enhanced inflation.…”

Cerebral venous congestion promotes blood-brain barrier disruption and neuroinflammation, impairing cognitive function in mice

“…Both rodent (Adamski et al 2018) and canine models of age-related heart failure could be quite relevant in that regard (Urfer et al 2017;Labinskyy et al 2007;Lei et al 2004;Lionetti et al 2005). Studies investigating the interaction of cerebral venous congestion-induced neuroinflammation and activation of inflammatory mechanisms by other comorbid conditions (Csiszar et al 2017;Tucsek et al 2014a, b;Leng et al 2017;Tucsek et al 2017;Toth et al 2013;Van Skike et al 2018) are also warranted. Prospective clinical studies on heart failure patients that include in the study design endpoints that reflect jugular venous reflux, cerebral venous pressure, microvascular damage, and neuroinflammation as well as cognitive performance (Carlson et al 2018) are also needed.…”

Advances and challenges in geroscience research: An update

“…Novel findings suggest that chronic infection with human cytomegalovirus (CMV) might be altering the balance of immune responses in aging. This is of particular interest to the geroscience community, since over 90% of adults 80 years of age or older exhibit persistent infection with CMV (1,24,31,44,54), which replicates in the vascular endothelial cells and may contribute to a number of multiorgan age-related microvascular pathologies.…”