Parvovirus B19 genotype specific amino acid substitution in NS1 reduces the protein's cytotoxicity in culture.
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.
Kivovich
Violetta
V
Pennsylvania State College of Medicine, Hershey, PA, USA.
Gilbert
Leona
L
Vuento
Matti
M
Naides
Stanley J
SJ
D019943:Amino Acid Substitution; D017209:Apoptosis / Q000187:drug effects*; D005434:Flow Cytometry; D005838:Genotype; D056945:Hep G2 Cells; D006801:Humans; D016732:Parvovirus B19, Human / Q000235:genetics* / Q000378:metabolism*; D013329:Structure-Activity Relationship; D017361:Viral Nonstructural Proteins / Q000737:chemistry / Q000235:genetics* / Q000633:toxicity*
D017361:Viral Nonstructural Proteins