Letter Regarding Article by Kühl et al, “High Prevalence of Viral Genomes and Multiple Viral Infections in the Myocardium of Adults With ‘Idiopathic’ Left Ventricular Dysfunction”
2005; Lippincott Williams & Wilkins; Volume: 112; Issue: 15 Linguagem: Inglês
10.1161/circulationaha.105.547794
ISSN1524-4539
AutoresUmesh C. Sharma, Saraswati Pokharel, Jos G. Maessen,
Tópico(s)Cardiovascular Effects of Exercise
ResumoHomeCirculationVol. 112, No. 15Letter Regarding Article by Kühl et al, "High Prevalence of Viral Genomes and Multiple Viral Infections in the Myocardium of Adults With 'Idiopathic' Left Ventricular Dysfunction" Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBLetter Regarding Article by Kühl et al, "High Prevalence of Viral Genomes and Multiple Viral Infections in the Myocardium of Adults With 'Idiopathic' Left Ventricular Dysfunction" Umesh C. Sharma, MBBS, MSc, Saraswati Pokharel, MBBS, PhD and Jos G. Maessen, MD, PhD Umesh C. SharmaUmesh C. Sharma University Hospital Maastricht, Maastricht, The Netherlands , Saraswati PokharelSaraswati Pokharel University Hospital Maastricht, Maastricht, The Netherlands and Jos G. MaessenJos G. Maessen University Hospital Maastricht, Maastricht, The Netherlands Originally published11 Oct 2005https://doi.org/10.1161/CIRCULATIONAHA.105.547794Circulation. 2005;112:e265To the Editor:Kühl and colleagues1 reported a high prevalence of viral genomes and multiple viral infections in the myocardium of adult patients with dilated cardiomyopathy (DCM). The authors suggested that myocardial persistence of various viruses can play a role in the pathogenesis of DCM. Of the 245 DCM patients, amplification of the viral genome was possible only in 67.4%.1 Failure to detect the viral genome from the tissues of remaining 32.6% of the patients suggests an absent or undetectable viral load at the time of the tissue sampling. However, the viruses have a propensity to develop a "hit-and-run" event in which cellular transformation is initiated through an initial "hit" that results in the loss of function, followed by viral disappearance ("run").2 This concept raises the possibility of an etiologic role of viral agents in the heart even in the absence of any viral gene or protein expression at the time of biopsy. Interestingly, the immune system responds to the earliest infection by producing antibodies that are detectable in the serum even in the absence of the viruses. In agreement with this phenomenon, the authors could detect positive parvovirus B19 (PVB19) IgG antibody in 39.2% of the PVB19 PCR-negative patients.On the other hand, viruses can evade the immune system if they become integrated to the host genome before thymic education (ie, early childhood).3 This can explain the authors' observations in 4.8% of the cases in which, despite the PVB19-PCR positivity, they could not detect PVB19 IgG antibody. Therefore, it would be interesting to inquire whether these patients suffered from PVB19 infection in their early childhood.1 Kühl U, Pauschinger M, Noutsias M, Seeberg B, Bock T, Lassner D, Poller W, Kandolf R, Schultheiss HP. High prevalence of viral genomes and multiple viral infections in the myocardium of adults with "idiopathic" left ventricular dysfunction. Circulation. 2005; 111: 887–893.LinkGoogle Scholar2 Galloway DA, McDougall JK. The oncogenic potential of herpes simplex viruses: evidence for a "hit-and-run" mechanism. Nature. 1983; 302: 21–24.CrossrefMedlineGoogle Scholar3 Heath WR, Scott HS. Immunology: education and promiscuity. Nature. 2002; 420: 468–469.CrossrefMedlineGoogle ScholarcirculationahaCirculationCirculationCirculation0009-73221524-4539Lippincott Williams & WilkinsResponseKühl Uwe, , PhD, MD, Pauschinger Matthias, , MD, Noutsias Michel, , MD, Seeberg Bettina, , MD, Lassner Dirk, , PhD, Poller Wolfgang, , MD, Schultheiss Heinz-Peter, , MD, Bock Thomas, , PhD, and Kandolf Reinhard, , PhD, MD11102005With respect to the interesting comments of Sharma et al about our article,1 we would like to make the 2 following points. First, the "hit-and-run" hypothesis is of interest. Virus-induced loss of function followed by virus elimination but lack of functional restoration may be either due to irreversibility of the damage (eg, cardiomyocyte loss and/or fibrosis) or to persistent nonviral damage such as that imposed by chronic autoimmunity. We agree with Sharma et al in this respect; however, the mere existence of PVB19 IgG antibody allows no conclusion that the virus has indeed entered the heart at any time. The determinants of organ and tissue targeting of PVB19 in humans are unknown so far, and there may be specific individual factors that are required to allow cardiac entry of the virus. We are currently trying to shed some light on such factors (virus receptors, etc), but virus targeting mechanisms are usually very complex in vivo.Second, viruses may indeed evade the immune system when integrating into the host genome before thymic education. Whereas genomic integration at variable (usually very low) rates has been shown for many other viruses, there is so far no evidence for such events in PVB19. For other parvoviruses, however, the adeno-associated viruses (AAVs), which in contrast to PVB19 are dependent on helper functions from other viruses (eg, adenoviruses, herpesviruses), rare integration events have been documented, but AAVs have not been detected in human hearts so far. Immune evasion as discussed by Sharma et al would be plausible for PVB19 only if genomic integration were documented for this virus species, too. Currently, there is no evidence whatsoever for such events. Previous Back to top Next FiguresReferencesRelatedDetailsCited By Benedetto U, Raja S, Albanese A, Amrani M, Biondi-Zoccai G and Frati G (2014) Searching for the second best graft for coronary artery bypass surgery: a network meta-analysis of randomized controlled trials, European Journal of Cardio-Thoracic Surgery, 10.1093/ejcts/ezu111, 47:1, (59-65), Online publication date: 1-Jan-2015. Bajpai V and Andreadis S (2012) Stem Cell Sources for Vascular Tissue Engineering and Regeneration, Tissue Engineering Part B: Reviews, 10.1089/ten.teb.2011.0264, 18:5, (405-425), Online publication date: 1-Oct-2012. Peng H, Liu J, Andreadis S and Swartz D (2011) Hair Follicle-Derived Smooth Muscle Cells and Small Intestinal Submucosa for Engineering Mechanically Robust and Vasoreactive Vascular Media, Tissue Engineering Part A, 10.1089/ten.tea.2010.0109, 17:7-8, (981-990), Online publication date: 1-Apr-2011. de Oliveira E and Ellis S (2008) Myocyte Regeneration Reperfusion Therapy for Acute Myocardial Infarction, 10.3109/9781420019179.018, (300-315), Online publication date: 1-Mar-2008. October 11, 2005Vol 112, Issue 15 Advertisement Article InformationMetrics https://doi.org/10.1161/CIRCULATIONAHA.105.547794PMID: 16216969 Originally publishedOctober 11, 2005 PDF download Advertisement SubjectsCardiomyopathyContractile FunctionHeart Failure
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