Genetic diversity, haplotype analysis, and risk factor assessment of hepatitis A virus isolates from the West Bank, Palestine during the period between 2014 and 2016

Abstract

Background Hepatitis A virus (HAV) infection is one of the major causes of acute viral hepatitis. HAV genotypes and its genetic diversity is rarely investigated in our region as well as worldwide. Aims The aims of the present study were to determine the HAV genotypes and its risk factors and to investigate the genetic diversity of the HAV isolates in the West Bank, Palestine. Study design A cohort of 161 clinically and laboratory-confirmed HAV (IgM-positive) cases and 170 apparently healthy controls from all the districts of the West Bank, Palestine during the period of 2014 to 2016 were tested for HAV infection using IgM antibodies, RT-PCR and sequence analysis of the VP3/VP1 junction region of the HAV genome. Phylogenetic analysis, genetic diversity and haplotypes analysis were used to characterize the VP3/VP1 sequences. Results All the 34 sequences of the HAV were found to be of HAV-IB sub-genotype. The phylogenetic analysis showed four main clusters with cluster III exclusively consisting of 18 Palestinian isolates (18/23-78%), but with weak bootstrap values. A high haplotype diversity (Hd) and low nucleotide diversity (π) were observed. Cluster III showed high number of haplotypes (h = 8), but low haplotype (gene) diversity (Hd = 0.69). A total of 28 active haplotypes with some consisting of more than one sequence were observed using haplotype network analysis. The Palestinian haplotypes are characterized by closely related viral haplotypes with one SNV away from each other which ran parallel to cluster III in the phylogenetic tree. A smaller Palestinian haplotype (4 isolates) was three SNVs away from the major haplotype cluster (n = 10) and closer to others haplotypes from Iran, Spain, and South Africa. Young age, low level of parent’s education, infrequent hand washing before meals, and drinking of un-treated water were considered the major HAV risk factors in the present study. Conclusion Haplotype network analysis revealed haplotype variation among the HAV Palestinian sequences despite low genetic variation and nucleotide diversity. In addition, this study reconfirmed that age and parent’s level of education as HAV risk factors, while hand washing and treating drinking water as protective factors.

The Evolutionary Landscape of SARS-CoV-2 Variant B.1.1.519 and Its Clinical Impact in Mexico City

“…Additionally, an MJN will infer additional sequence types that minimize the inferred length; such inferred sequences can be considered biologically as unseen or extinct sequences. The distance between two sequence types will equal the number of nucleotide differences observed between them (Hamming distance) [43][44][45].…”

The evolutionary landscape of SARS-CoV-2 variant B.1.1.519 and its clinical impact in Mexico City

“…Additionally, an MJN will infer additional sequence types that minimize the inferred length; such inferred sequences can be considered biologically as unseen or extinct sequences. The distance between two sequence types will equal the number of nucleotide differences observed between them (Hamming distance) [38][39][40] . Similarly, the Alpha VOC has been associated with an increased risk of hospitalization and greater disease severity or death 46,47 .…”

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“…Haplotype combination and analysis is a useful statistical analysis strategy that combines multi-loci together to discover genetic predictors of disease incidence risk [ 27 , 28 ]. Our study found that both haplotypes, including AT at rs1057141 and rs2228396 and AAT at rs1057141, rs1135216 and rs2228396, were significantly associated with increased PTB risk.…”