Longer duration of viremia and unique amino acid substitutions in a hepatitis A virus strain [corrected] associated with Guillain-Barré syndrome (GBS).
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.
Joshi
Madhuri S
MS
National Institute of Virology, Pune, Maharashtra, India.
Cherian
Sarah S
SS
Bhalla
Shilpa
S
Chitambar
Shobha D
SD
D019943:Amino Acid Substitution; D016000:Cluster Analysis; D018985:Epitopes, B-Lymphocyte / Q000235:genetics; D016679:Genome, Viral; D020275:Guillain-Barre Syndrome / Q000150:complications*; D006506:Hepatitis A / Q000473:pathology / Q000821:virology*; D030041:Hepatitis A virus / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D007194:India; D008958:Models, Molecular; D020125:Mutation, Missense; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D017385:Sequence Homology; D055672:Static Electricity; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics*; D014766:Viremia
D018985:Epitopes, B-Lymphocyte; D014764:Viral Proteins