Cytomegalovirus latency exacerbates cardiac inflammation and tissue remodeling after myocardial infarction
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Background
Epidemiological studies have consistently associated cytomegalovirus (CMV) seropositivity with adverse cardiovascular outcomes. However, the mechanisms by which CMV infection impacts pathophysiological mechanisms in the heart remain poorly understood. In this study, we sought to dissect how latent murine CMV infection impacts cardiac immune cell dynamics at steady-state and during post-myocardial infarction (MI) repair.
Methods
Experimental MI studies were conducted in C57BL/6J mice previously infected with murine CMV (MCMV). In situ inflammatory responses were characterized by spectral flow cytometry, bulk and single-cell RNA / T cell receptor sequencing, whereas cardiac function was monitored by echocardiography and magnetic resonance imaging (cMRI). Moreover, we retrospectively assessed the CMV serostatus in a well-characterized patient cohort with longitudinal cMRI data available and performed bulk T cell receptor sequencing on peripheral blood and myocardial samples to identify CMV-specific TCRs.
Results
Our findings show that exposure to MCMV induces long-term changes in the cardiac transcriptional profile and alterations in cardiac-resident immune cell populations, including the establishment of virus-specific memory CD8 + T cell residency. Compared to infarcted controls, mice previously exposed to MCMV exhibited stronger inflammatory responses, marked by increased CD8 + T cell infiltration, and worsened cardiac function following MI. These observations in mice were supported by data from CMV-seropositive MI patients, who harbored CMV-responsive T cells in the heart.
Conclusions
Our findings demonstrate that latent CMV infection leads to long-term changes in the cardiac microenvironment, which ultimately impair post-MI healing outcomes.
