Back to Search
Start Over
Parvovirus B19 genotype specific amino acid substitution in NS1 reduces the protein's cytotoxicity in culture.
- Source :
-
International journal of medical sciences [Int J Med Sci] 2010 May 25; Vol. 7 (3), pp. 110-9. Date of Electronic Publication: 2010 May 25. - Publication Year :
- 2010
-
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.
- Subjects :
- Amino Acid Substitution
Flow Cytometry
Genotype
Hep G2 Cells
Humans
Structure-Activity Relationship
Viral Nonstructural Proteins chemistry
Apoptosis drug effects
Parvovirus B19, Human genetics
Parvovirus B19, Human metabolism
Viral Nonstructural Proteins genetics
Viral Nonstructural Proteins toxicity
Subjects
Details
- Language :
- English
- ISSN :
- 1449-1907
- Volume :
- 7
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- International journal of medical sciences
- Publication Type :
- Academic Journal
- Accession number :
- 20567611
- Full Text :
- https://doi.org/10.7150/ijms.7.110