Longer duration of viremia and unique amino acid substitutions in a hepatitis A virus strain [corrected] associated with Guillain-Barré syndrome (GBS).
Autor(es): Joshi Madhuri S.; Cherian Sarah S.; Bhalla Shilpa; Chitambar Shobha D.
Resumo: The molecular characteristics of hepatitis A virus (HAV) have been studied widely though there is a paucity of data on the correlation with virological and serological findings. In the present study, the whole genome of an Indian HAV strain associated with Guillain-Barré syndrome (GBS) was characterized vis-à-vis two other Indian HAV genotype IIIA strains, associated with a self-limiting disease. The percentage nucleotide divergence displayed by the Indian strains (CP-IND, PN-IND, and GBS-IND) varied from 3 to 6, whereas the percentage amino acid divergence varied from 0.1 to 0.7 as compared to the other HAV IIIA strains (n = 5) available in the GenBank. The GBS-IND strain showed an increased rate of nonsynonymous substitutions as well as a larger number of unique and heterologous amino acid substitutions compared to the HAV IIIA GenBank strains. These amino acid substitutions in the GBS-IND strain were detected in a nonstructural protein (2C-251F) and the B-cell epitope regions of structural proteins (VP1-29E, VP1-91S, VP3-50Y, and VP4-5S). In a comparative analysis of HAV strains, homology-based models of the capsid proteins indicated a localized alteration in the surface charge distribution on the VP1 protein of GBS-IND strain and involvement of its unique amino acid substitutions in the predicted antigenic determinants. Overall, the study suggests that the unique amino acid substitutions in the GBS-IND strain may have contributed to neutralization escape of the virus leading to a longer duration of viremia.
Imprenta: Journal of Medical Virology, v. 82, n. 6, p. 913-919, 2010
Identificador do objeto digital: 10.1002/jmv.21757
Descritores: Guillain-Barre Syndrome - Cell ; Guillain-Barre Syndrome - Cytopathology ; Guillain-Barre Syndrome - Genome ; Guillain-Barre Syndrome - Molecular Structure ; Guillain-Barre Syndrome - Pathogenesis ; Guillain-Barre Syndrome - Proteins ; Guillain-Barre Syndrome - Inflammation ; Guillain-Barre Syndrome - Viral infections ; Guillain-Barre Syndrome - Serological diagnosis ; Guillain-Barre Syndrome - Virus ; Guillain-Barre Syndrome - Molecular screening ; Guillain-Barre Syndrome - Public health
Data de publicação: 2010
