Enterovirus but not Parvovirus B19 is associated with idiopathic dilated cardiomyopathy and endomyocardial CD3, CD68, or HLA‐DR expression

Abstract

We assessed Enterovirus (EV) &Parvovirus B19 (PVB19) genomes and CD3, CD68&HLA-DR detection in dilated cardiomyopathies (DCM). EV&PVB19 genomes and CD3, CD68&HLA-DR were detected by PCR and immunohistochemistry assays in 115 endomyocardial biopsies obtained in 13 idiopathic DCM (iDCM) and 10 explained DCM (eDCM) patients. Results were compared with those of 47 atrial surgical samples (47 surgery controls) and 22 autoptic cardiac samples (11 healthy heart controls) (2008-2014, Reims, France). EV was detected in 23.1% of iDCM patients but not in eDCM and controls (P = 0.003) (viral load 803 copies/μg). PVB19 was detected in 76.9%, 80.0%, 63.6% and 78.2% of iDCM, eDCM, healthy heart and surgery controls (P = 0.99) with a mean viral load of 413, 346, 1,428, and 71 copies/μg. CD3, CD68 or HLA-DR were detected in 100 and 50% of EV and PVB19 "mono-infected" iDCM patients. EV was exclusively detected in iDCM cases in association with CD3, CD68, or HLA-DR indicating that EV could be an etiological cause in a subset of iDCM cases. By contrast the equal frequent detection of PVB19 in iDCM cases and controls without association with CD3, CD68, or HLA-DR suggested that PVB19 could be a bystander in many DCM cases. J. Med. Virol. 89:55-63, 2017. © 2016 Wiley Periodicals, Inc.

Revealing enterovirus infection in chronic human disorders: An integrated diagnostic approach

“…As shown in Table S4B, comparison with Ct values obtained using known copy numbers of pUC57-5UTR plasmids allowed to estimate the mean viral load of PPS samples at 177 genome copies/ml in cell culture medium (range 120–230/ml), and that of T1D samples at 470 genome copies/ml in cell culture medium (range 220–620/ml). Thus, the viral load in cell cultures exposed to samples of PPS and T1D patients is comparable to what documented in cardiac tissue of idiopathic cardiomyopathy [about 500 EV genome copies/μg of total extracted nucleic acids 15 ]. The low virus levels indicate that replication-defective agents play a role in chronic EV infection.

Figure 2Results of end-point PCR of quantitated pU57 plasmids containing the 5′UTR region of CV-A6, CV-B3, PV-1, EV-D68 (representative enteroviruses of the A, B, C, and D species).

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“…Virologists have provided evidence for naturally-occurring enteroviral isolates characterized by 5′UTR deletions in human myocardium 13, 15, 46 as well as in mouse pancreas and myocardium 32, 46 . The 5′UTR region of EVs includes the internal ribosomal entry site (IRES) consisting of five domains.…”

“…Persistent EV infections are frequently encountered in immunodeficiency 6 , but long-term infection of immunocompetent hosts is still a matter of debate. Evidence is so far limited to certain neurologic 7, 8 , endocrine 9–11 , and cardiac disorders 12–15 . It is also known that vaccine-derived polioviruses may be isolated from sewage in places where no known immunodeficient persons live, suggesting that they can be shed by healthy persons chronically infected with the virus 16 .…”

“…Though EVs are cytolytic to their host cells 19 , some studies indicate that subclinical EV infection may be associated with lifelong disorders such as the post-polio syndrome (PPS) 20, 21 , myasthenia gravis 22 , autoimmune thyroiditis 23 , type 1 diabetes (T1D) 9, 10, 18 , chronic viral cardiomyopathy (CVC) 12–15 . The hypothesis that persistent EV infection may be linked to organ-specific autoimmunity and chronic disease is supported by recent results showing an incomplete humoral response to coxsackie B viruses in children who first developed insulin autoantibodies, then type 1 diabetes 24 (T1D).…”

Immunological and pathological consequences of coxsackievirus RNA persistence in the heart

“…), and during subsequent days they did not suffer weight loss indicative of a severe infection; we speculate that these animals may represent a parallel to the well-recognized phenomenon of human DCM patients who have enterovirus RNA + cardiac biopsies without any history suggestive of acute viral myocarditis. In a recent study of 23 DCM patients (N’Guyen et al, 2017), 10 individuals were classified as having “explained” DCM (eDCM), and the remaining 13 were considered to have idiopathic DCM (iDCM). Cardiac biopsies from both DCM groups, and samples from two control groups without DCM, were evaluated for the presence of nucleic acids of six different viruses; in all four groups, >80% of hearts contained genomes from at least one virus.…”