Parvovirus B19 DNA detectable in hearts of patients with dilated cardiomyopathy, but absent or inactive in blood

Abstract

Aims Parvovirus B19 (B19V) is often assumed to be a cause of dilated cardiomyopathy (DCM), based on the quantification of B19V DNA in endomyocardial biopsies (EMB). Whether the presence of B19V DNA correlates with active infection is still debated. Application of the enzyme endonuclease to blood samples results in degradation of B19V DNA remnants but leaves viral particles intact, which enables differentiation between active and past infection. In this study, the susceptibility to degradation by endonuclease of B19V DNA in blood was compared between DCM patients and a control group of recent B19V infections. Methods and results Twenty blood samples from 20 adult patients with DCM, who previously tested positive for B19V DNA in EMB and/or blood, were tested with B19V PCR before and after application of endonuclease to the samples. Six blood samples tested positive for B19V DNA with a mean viral load of 2.3 × 10 4 IU/mL. In five samples, B19V DNA became undetectable after endonuclease (100% load reduction); in one sample DNA load showed a 23% log load reduction (viral load before endonuclease: 9.1 × 10 4 IU/mL; after: 6.5 × 10 3 IU/mL). Presence of cardiac inflammation did not differ between patients with B19V DNAemia (1/4) and patients without B19V DNAemia (6/14) (P value = 1.0). In all 18 control samples of proven recent B19V infections, DNA remained detectable after application of endonuclease, showing only a mean log load reduction of 2.3% (mean viral load before endonuclease: 8.1 × 10 11 IU/mL; after: 8.0 × 10 11 IU/mL). Load reduction differed significantly between the DCM group and the control group; indicating the presence of intact viral particles in the control group with proven active infection and the presence of DNA remnants in the DCM group (P value = 0.000). Conclusion During recent B19V infection, viral DNA levels in blood were unaffected by endonuclease. In contrast, B19V DNA in blood in patients with DCM became undetectable or strongly reduced after application of endonuclease. Circulating viral DNA in this subset of patients with presumed parvovirus-associated DCM does not consist of intact viral particles. Viral replicative activity cannot be assumed from demonstrating B19V DNA in cardiac tissue or in blood in DCM patients.

Prevalence, tropism, and activity of cutavirus in circulating blood lymphocytes, stool, and skin biopsy specimens of patients with cutaneous T‐cell lymphoma and parapsoriasis en plaques

“…Nevertheless, stool samples from CTCL or PP patients have not been studied previously, since they are not routinely collected from this patient group. Previous studies on parvovirus B19 have shown that the parvovirus capsid protects the genome against nucleases like Benzonase 30,31 . In the current study, we were able to show, with the Benzonase‐PCR assay, the presence of protecting viral capsids in CuV PCR‐positive stools of two patients (one CTCL, one PP), suggesting that the patients were excreting infectious virions in their stools—despite their infections had persisted for at least 5 years.…”

“…Previous studies on parvovirus B19 have shown that the parvovirus capsid protects the genome against nucleases like Benzonase. 30,31 In the current study, we were able to show, with the Benzonase-PCR assay, the presence possess the skin-tropic memory phenotype. 32 Furthermore, it is known that also malignant T cells in MF show great intra-tumoral genetic heterogeneity, 33 the implications of which in relation to CuV would also need to be examined.…”

Advancing Precision Medicine in Myocarditis: Current Status and Future Perspectives in Endomyocardial Biopsy-Based Diagnostics and Therapeutic Approaches

“…Viral latency and active infection may alternate in individuals, accelerating LV dysfunction and development of DCM [142]. B19V is commonly found in EMBs of patients with DCM, whereas little to no correlation was found with blood virus titers, and no detection can be achieved with imaging, underlining the need for a comprehensive biopsy-driven diagnostic workup in cases of DCM of unclear etiology to allow for sufficient patient characterization [143]. Finally, the presence of B19V in the pediatric heart likely increases the risk of graft loss [103].…”

Transient Parvovirus B19 DNAemia After Kidney Transplantation: A 2-Sided Story

“…Due to an adult seroprevalence of 60%–70%, many recipients will not be susceptible [ 13 ]. Detectable DNA may originate from intact viral particles, causing true infection, or from DNA remnants released from previously infected cells [ 10 , 14–16 ]. Application of an endonuclease-based assay can differentiate between these 2 scenarios [ 10 ].…”