Proline-Rich Hypervariable Region of Hepatitis E Virus: Arranging the Disorder
2020
Milagros Muñoz-Chimeno | Alejandro Cenalmor | Maira Alejandra Garcia-Lugo | Marta Hernandez | David Rodriguez-Lazaro | Ana Avellon
The hepatitis E virus (HEV) hypervariable region (HVR) presents the highest divergence of the entire HEV genome. It is characteristically rich in proline, and so is also known as the &ldquo:polyproline region&rdquo: (PPR). HEV genotype 3 (HEV-3) exhibits different PPR lengths due to insertions, PPR and/or RNA-dependent RNA polymerase (RdRp) duplications and deletions. A total of 723 PPR-HEV sequences were analyzed, of which 137 HEV-3 sequences were obtained from clinical specimens (from acute and chronic infection) by Sanger sequencing. Eight swine stool/liver samples were also analyzed. N- and C-terminal fragments were confirmed as being conserved, but they harbored differences between genotypes and were not proline-plentiful regions. The genuine PPR is the intermediate region between them. HEV-3 PPR contains a higher percentage (30.4%) of prolines than other genotypes. We describe for the first time: (1) the specific placement of HEV-3 PPR rearrangements in sites 1 to 14 of the PPR, noting that duplications are more frequently attached to sites 11 and 12 (AAs 74&ndash:79 and 113&ndash:118, respectively): (2) the cadence of repetitions follows a circular-like pattern of blocks A to J, with F, G, H, and I being the most frequent: (3) a previously unreported insertion homologous to apolipoprotein C1: and (4) the increase in frequency of potential N-glycosylation sites and differences in AAs composition related to duplications.
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