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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Main Authors: Milagros Muñoz-Chimeno, Alejandro Cenalmor, Maira Alejandra Garcia-Lugo, Marta Hernandez, David Rodriguez-Lazaro, Ana Avellon
Format: Article
Language:English
Published: MDPI AG 2020-09-01
Series:Microorganisms
Subjects:
Online Access:https://www.mdpi.com/2076-2607/8/9/1417
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author Milagros Muñoz-Chimeno
Alejandro Cenalmor
Maira Alejandra Garcia-Lugo
Marta Hernandez
David Rodriguez-Lazaro
Ana Avellon
author_facet Milagros Muñoz-Chimeno
Alejandro Cenalmor
Maira Alejandra Garcia-Lugo
Marta Hernandez
David Rodriguez-Lazaro
Ana Avellon
author_sort Milagros Muñoz-Chimeno
collection DOAJ
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 doaj.art-87bec504889148f89f418674f0a1dd802023-11-20T13:46:55ZengMDPI AGMicroorganisms2076-26072020-09-0189141710.3390/microorganisms8091417Proline-Rich Hypervariable Region of Hepatitis E Virus: Arranging the DisorderMilagros Muñoz-Chimeno0Alejandro Cenalmor1Maira Alejandra Garcia-Lugo2Marta Hernandez3David Rodriguez-Lazaro4Ana Avellon5Hepatitis Unit, National Center of Microbiology, Carlos III Institute of Health, 28220 Madrid, SpainHepatitis Unit, National Center of Microbiology, Carlos III Institute of Health, 28220 Madrid, SpainHepatitis Unit, National Center of Microbiology, Carlos III Institute of Health, 28220 Madrid, SpainLaboratorio de Biología Molecular y Microbiología, Instituto Tecnológico Agrario de Castilla y León (ITACyL), 47071 Valladolid, SpainMicrobiology Division, Faculty of Sciences, University of Burgos, 09001 Burgos, SpainHepatitis Unit, National Center of Microbiology, Carlos III Institute of Health, 28220 Madrid, SpainThe 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.https://www.mdpi.com/2076-2607/8/9/1417hepatitis E virusHEVPPRHVRhypervariablehyper-proline
spellingShingle Milagros Muñoz-Chimeno
Alejandro Cenalmor
Maira Alejandra Garcia-Lugo
Marta Hernandez
David Rodriguez-Lazaro
Ana Avellon
Proline-Rich Hypervariable Region of Hepatitis E Virus: Arranging the Disorder
Microorganisms
hepatitis E virus
HEV
PPR
HVR
hypervariable
hyper-proline
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 hepatitis E virus
HEV
PPR
HVR
hypervariable
hyper-proline
url https://www.mdpi.com/2076-2607/8/9/1417
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