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Proline-Rich Hypervariable Region of Hepatitis E Virus: Arranging the Disorder

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 “polyproline region” (PPR). HEV genotype 3 (HEV-3) exhibits different PPR lengths due to insertions, PPR and/or RNA-d...

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Autores principales: Muñoz-Chimeno, Milagros, Cenalmor, Alejandro, Garcia-Lugo, Maira Alejandra, Hernandez, Marta, Rodriguez-Lazaro, David, Avellon, Ana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7564002/
https://www.ncbi.nlm.nih.gov/pubmed/32942608
http://dx.doi.org/10.3390/microorganisms8091417
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author Muñoz-Chimeno, Milagros
Cenalmor, Alejandro
Garcia-Lugo, Maira Alejandra
Hernandez, Marta
Rodriguez-Lazaro, David
Avellon, Ana
author_facet Muñoz-Chimeno, Milagros
Cenalmor, Alejandro
Garcia-Lugo, Maira Alejandra
Hernandez, Marta
Rodriguez-Lazaro, David
Avellon, Ana
author_sort Muñoz-Chimeno, Milagros
collection PubMed
description 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 “polyproline region” (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 74–79 and 113–118, 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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spelling pubmed-75640022020-10-27 Proline-Rich Hypervariable Region of Hepatitis E Virus: Arranging the Disorder Muñoz-Chimeno, Milagros Cenalmor, Alejandro Garcia-Lugo, Maira Alejandra Hernandez, Marta Rodriguez-Lazaro, David Avellon, Ana Microorganisms Article 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 “polyproline region” (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 74–79 and 113–118, 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. MDPI 2020-09-15 /pmc/articles/PMC7564002/ /pubmed/32942608 http://dx.doi.org/10.3390/microorganisms8091417 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Muñoz-Chimeno, Milagros
Cenalmor, Alejandro
Garcia-Lugo, Maira Alejandra
Hernandez, Marta
Rodriguez-Lazaro, David
Avellon, Ana
Proline-Rich Hypervariable Region of Hepatitis E Virus: Arranging the Disorder
title Proline-Rich Hypervariable Region of Hepatitis E Virus: Arranging the Disorder
title_full Proline-Rich Hypervariable Region of Hepatitis E Virus: Arranging the Disorder
title_fullStr Proline-Rich Hypervariable Region of Hepatitis E Virus: Arranging the Disorder
title_full_unstemmed Proline-Rich Hypervariable Region of Hepatitis E Virus: Arranging the Disorder
title_short Proline-Rich Hypervariable Region of Hepatitis E Virus: Arranging the Disorder
title_sort proline-rich hypervariable region of hepatitis e virus: arranging the disorder
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7564002/
https://www.ncbi.nlm.nih.gov/pubmed/32942608
http://dx.doi.org/10.3390/microorganisms8091417
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