doi: 10.1161/CIRCULATIONAHA.105.546168
(Circulation. 2005;112:e145.)
© 2005 American Heart Association, Inc.
Correspondence |
Letter Regarding Article by Tschöpe et al, "High Prevalence of Cardiac Parvovirus B19 Infection in Patients With Isolated Left Ventricular Diastolic Dysfunction"
Hypertension and Vascular Research Division, Henry Ford Health System, Detroit, Mich
Department of Cardio-thoracic Surgery, University Hospital Maastricht, Maastricht, The Netherlands
Tschöpe and colleagues reported a high prevalence of Parvovirus B19 (PVB19) infection in patients with unexplained diastolic dysfunction. The authors suggested that PVB19-induced endothelial dysfunction could have contributed to the development of the observed diastolic dysfunction.1 Given the highly sensitive nature of nested/quantitative polymerase chain reaction technology, the reported titer of 102 to 103 PVB19 genome equivalents per microgram of nucleic acid is modest. Therefore, it is hard to presume that this low-level genomic presence of PVB19 per se could have impaired coronary microcirculation to the extent of inducing diastolic dysfunction. As in many other viruses, the icosahedral capsid of PVB19 consists of a range of amino acids with a potential to trigger the autoimmune reaction in the tissues.2 The extent of autoantibody production depends on the amino acid sequence similarity between the virus and human proteins. In our database search, we found a sequence match of 6 amino acids between the PVB19 surface protein and human Golgi body–specific antigenic protein, golgin-160 (PVB19 VP1/2 surface protein, NEKEQLKQLQ; human golgin-160, WLKEQLKQYR).3 Therefore, the antibodies and T-lymphocytes directed against PVB19 VP1/2 surface protein potentially cross-reacted against human protein golgin-160, leading to tissue damage. Because the autoantibody production is independent of viral load, the echocardiographic and catheterization findings of diastolic dysfunction can be reconciled to low viral load in these patients. Our suggestion is to test the presence of anti-PVB19 VP1/2 surface protein antibodies in the sera obtained from the 70 patients reported in this study and perform competition ELISA to detect the antibody cross-reactivity because of the molecular mimicry between PVB19 VP1/2 surface protein and human golgin-160.
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1. Tschope C, Bock CT, Kasner M, Noutsias M, Westermann D, Schwimmbeck PL, Pauschinger M, Poller WC, Kuhl U, Kandolf R, Schultheiss HP. High prevalence of cardiac parvovirus B19 infection in patients with isolated left ventricular diastolic dysfunction. Circulation. 2005; 111: 879–886.
2. Hopp TP, Woods KR. Prediction of protein antigenic determinants from amino acid sequences. Proc Natl Acad Sci U S A. 1981; 78: 3824–3828.
3. Fritzler MJ, Hamel JC, Ochs RL, Chan EK. Molecular characterization of two human autoantigens: unique cDNAs encoding 95- and 160-kD proteins of a putative family in the Golgi complex. J Exp Med. 1993; 178: 49–62.
Department of Cardiology and Pneumology, Charité—University Medicine Berlin, Campus Benjamin Franklin, Berlin, Germany
Department of Molecular Pathology, University Hospital of Tuebingen, Tuebingen, Germany
Sharmaand colleagues provide a thoughtful discussion of one way to reconcile low cardiac parvovirus B19 (PVB19) loads with clinically significant cardiac dysfunction, with regard to our recent article in Circulation.1 We fully agree that cross-reactive humoral and/or cellular immune reactions against, for example, cellular golgin-160 and parvoviral VP1/2 surface protein may have the potential to incite a chronic autoimmune process involved in the pathogenesis of PVB19-associated cardiac dysfunction. A search for anti-PVB19 VP1/2 proteins in the patients’ sera as well as competition ELISA to detect molecular mimicry seems worthwhile. We would like to emphasize, however, that alternative/additional approaches may explain clinical disease at low virus load. First, chronic low level transcription of virus-encoded multifunctional proteins such as NS1 may dysregulate or reprogram sensitive cardiac signaling pathways in such a way that insidiously progressive cardiac dysfunction ensues. It has been shown that genetic dysfunction of such pathways may result not only in gross morphological anomalies of the heart but also in more subtle functional disturbances. A genome-wide screening for the possible induction of such disturbances in PVB19-infected cardiovascular cells may be helpful to solve this question. Second, the time course to clinically apparent cardiac dysfunction may be discontinuous in the following sense: Any chronic low virus load may be intermittently enhanced by
Response
1 order of magnitude when co-infection with a "secondary" virus occurs, which provides helper functions in trans for the "primary" parvovirus. We are investigating this scenario by evaluating the time course of clinical disease in patients harboring 2 cardiotropic viruses, as described in Kühl et al.2 In summary, all of the above approaches may shed light on the molecular links between PVB19 infections and human heart disease.
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This study was supported by the Deutsche-Forschungsgesellschaft (SFB-TR 19 to Drs Tschöpe and Bock).
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1. Tschope C, Bock CT, Kasner M, Noutsias M, Westermann D, Schwimmbeck PL, Pauschinger M, Poller WC, Kuhl U, Kandolf R, Schultheiss HP. High prevalence of cardiac parvovirus B19 infection in patients with isolated left ventricular diastolic dysfunction. Circulation. 2005; 111: 879–886.
2. 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.
Related Article:
Circulation 2005 112: 1519.
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