HIV patients, healthy aging and transplant recipients can reveal the hidden footprints of CMV

Abstract

Cytomegalovirus (CMV) is a β-herpesvirus. Latent infections are common in all populations. However age-associated increases in levels of CMV-reactive antibody are testament to repeated reactivations and periods of viral replication. CMV has been associated with several diseases of aging, including vasculopathy and neurocognitive impairment. These conditions occur at a younger age in persons with particularly high burdens of CMV - transplant recipients and people living with HIV. Here we define the "clinical footprints" as immunopathologies triggered by CMV that develop over many years. A high burden of CMV also drives accumulation of multifunctional terminally-differentiated αβ T-cells, a novel population of Vδ2 γδ T-cells, and a population of CD56 NK cells lacking a key regulatory molecule. An understanding of these "immunological footprints" of CMV may reveal how they collectively promote the "clinical footprints" of the virus. This is explored here in transplant recipients, HIV patients and healthy aging.

A high burden of cytomegalovirus marks poor vascular health in transplant recipients more clearly than in the general population

“…Indeed, reactivations from latency are rare in otherwise healthy individuals of this age group, but more common in the elderly . Overall, our data support a model whereby CMV lysate antibody levels are a useful surrogate marker of cumulative viral burden throughout an individual's lifetime, whereas the detection of CMV DNA is rare and stochastic …”

“…22 Overall, our data support a model whereby CMV lysate antibody levels are a useful surrogate marker of cumulative viral burden throughout an individual's lifetime, whereas the detection of CMV DNA is rare and stochastic. 23 Links between CMV reactivations and inflammation or stress are often cited, but clinical evidence is scant. One study associated CMV antibody levels with TNF-a and IL-6 in sera from young and elderly individuals.…”

Functional and clinical consequences of changes to natural killer cell phenotypes driven by chronic cytomegalovirus infections

“…However, there is an unmet need for a reliable metric of the burden of CMV in an individual that would predict vascular risk—especially in the general population where detection of CMV DNA is rare. NK cell phenotypes warrant consideration as a way to achieve this . In addition, NK cells may affect vascular endothelial function directly .…”

“…CMV can establish latency, so most people harbor CMV as a persistent life‐long infection with reactivations triggered by infection, immunosuppression, and stress or inflammation . CMV can cause severe disease in transplant recipients, newborns, and HIV‐infected patients, and has been associated with age‐related diseases . In our study of renal transplant recipients (RTR), CMV antibody levels are an independent marker of poor vascular endothelial function assessed using flow‐mediated dilatation (FMD).…”

“…3 CMV can cause severe disease in transplant recipients, newborns, and HIV-infected patients, and has been associated with age-related diseases. 4 In our study of renal transplant recipients (RTR), CMV antibody levels are an independent marker of poor vascular endothelial function assessed using flowmediated dilatation (FMD). The association with CMV antibodies was stronger than any plasma markers of vascular health (eg., ICAM-1, VCAM-1) in RTR (Lee et al, submitted for publication).…”