{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T04:11:41Z","timestamp":1790395901667,"version":"4.1.0"},"reference-count":43,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2020,9,15]],"date-time":"2020-09-15T00:00:00Z","timestamp":1600128000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["MPY 501-19"],"award-info":[{"award-number":["MPY 501-19"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>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 \u201cpolyproline region\u201d (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\u201379 and 113\u2013118, 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.<\/jats:p>","DOI":"10.3390\/microorganisms8091417","type":"journal-article","created":{"date-parts":[[2020,9,15]],"date-time":"2020-09-15T10:24:09Z","timestamp":1600165449000},"page":"1417","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Proline-Rich Hypervariable Region of Hepatitis E Virus: Arranging the Disorder"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1178-1418","authenticated-orcid":false,"given":"Milagros","family":"Mu\u00f1oz-Chimeno","sequence":"first","affiliation":[{"name":"Hepatitis Unit, National Center of Microbiology, Carlos III Institute of Health, 28220 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0648-8353","authenticated-orcid":false,"given":"Alejandro","family":"Cenalmor","sequence":"additional","affiliation":[{"name":"Hepatitis Unit, National Center of Microbiology, Carlos III Institute of Health, 28220 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maira Alejandra","family":"Garcia-Lugo","sequence":"additional","affiliation":[{"name":"Hepatitis Unit, National Center of Microbiology, Carlos III Institute of Health, 28220 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6914-9987","authenticated-orcid":false,"given":"Marta","family":"Hernandez","sequence":"additional","affiliation":[{"name":"Laboratorio de Biolog\u00eda Molecular y Microbiolog\u00eda, Instituto Tecnol\u00f3gico Agrario de Castilla y Le\u00f3n (ITACyL), 47071 Valladolid, Spain"},{"name":"Microbiology Division, Faculty of Sciences, University of Burgos, 09001 Burgos, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8795-854X","authenticated-orcid":false,"given":"David","family":"Rodriguez-Lazaro","sequence":"additional","affiliation":[{"name":"Microbiology Division, Faculty of Sciences, University of Burgos, 09001 Burgos, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Avellon","sequence":"additional","affiliation":[{"name":"Hepatitis Unit, National Center of Microbiology, Carlos III Institute of Health, 28220 Madrid, Spain"},{"name":"CIBER Epidemiology and Public Health, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Aspinall, E.J., Couturier, E., Faber, M., Said, B., Ijaz, S., Tavoschi, L., Takkinen, J., Adlhoch, C., and The Country, E. 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