International Journal of Medical Sciences

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18 December 2017

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Int J Med Sci 2010; 7(3):110-119. doi:10.7150/ijms.7.110

Research Paper

Parvovirus B19 Genotype Specific Amino Acid Substitution in NS1 Reduces the Protein's Cytotoxicity in Culture

Violetta Kivovich1,2, Leona Gilbert2, Matti Vuento2, Stanley J. Naides3

1. Pennsylvania State College of Medicine/ Milton S. Hershey Medical Center, Hershey, PA, U.S.A.;
2. Department of Biological and Environmental Science and Nanoscience Center, University of Jyväskylä, Jyväskylä, Finland;
3. Quest Diagnostics Nichols Institute, San Juan Capistrano, CA, U.S.A.

Abstract

A clinical association between idiopathic liver disease and parvovirus B19 infection has been observed. Fulminant liver failure, not associated with other liver-tropic viruses, has been attributed to B19 in numerous reports, suggesting a possible role for B19 components in the extensive hepatocyte cytotoxicity observed in this condition. A recent report by Abe and colleagues (Int J Med Sci. 2007;4:105-9) demonstrated a link between persistent parvovirus B19 genotype I and III infection and fulminant liver failure. The genetic analysis of isolates obtained from these patients demonstrated a conservation of key amino acids in the nonstructural protein 1 (NS1) of the disease-associated genotypes. In this report we examine a conserved residue identified by Abe and colleagues and show that substitution of isoleucine 181 for methionine, as occurs in B19 genotype II, results in the reduction of B19 NS1-induced cytotoxicity of liver cells. Our results support the hypothesis that in the setting of persistent B19 infection, direct B19 NS1-induced cytotoxicity may play a role in idiopathic fulminant liver failure.

Keywords: Parvovirus, B19, Fulminant Liver Failure, Cytotoxicity, Apoptosis

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How to cite this article:
Kivovich V, Gilbert L, Vuento M, Naides SJ. Parvovirus B19 Genotype Specific Amino Acid Substitution in NS1 Reduces the Protein's Cytotoxicity in Culture. Int J Med Sci 2010; 7(3):110-119. doi:10.7150/ijms.7.110. Available from http://www.medsci.org/v07p0110.htm