{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,8]],"date-time":"2025-11-08T12:18:50Z","timestamp":1762604330582,"version":"build-2065373602"},"reference-count":28,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,7,20]],"date-time":"2022-07-20T00:00:00Z","timestamp":1658275200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"China Medical University, Taiwan","award":["CMU110-S-03","CMU110-MF-61","CMU109-MF-57","CMU109-S-09","MOST108-2320-B-039-039-MY3","MOST110-2923-B-039-001-MY3"],"award-info":[{"award-number":["CMU110-S-03","CMU110-MF-61","CMU109-MF-57","CMU109-S-09","MOST108-2320-B-039-039-MY3","MOST110-2923-B-039-001-MY3"]}]},{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["CMU110-S-03","CMU110-MF-61","CMU109-MF-57","CMU109-S-09","MOST108-2320-B-039-039-MY3","MOST110-2923-B-039-001-MY3"],"award-info":[{"award-number":["CMU110-S-03","CMU110-MF-61","CMU109-MF-57","CMU109-S-09","MOST108-2320-B-039-039-MY3","MOST110-2923-B-039-001-MY3"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Zika virus (ZIKV) is a positive-sense single-stranded RNA virus in the Flaviviridae, which is classified into two different lineages Asian and African. The outbreak of ZIKV Asian lineage isolates in 2015\u20132016 is associated with the increase in cases with prenatal microcephaly and Guillain\u2013Barr\u00e9 syndrome, and has sparked attention throughout the world. Genome sequence alignment and the analysis of Asian and African lineage isolates indicate that amino acid changes, particular in positively charged amino acid substitutions in the pr region of prM protein might involve a phenotypic change that links with the global outbreak of ZIKV Asian-lineage. The study generated and characterized the virological properties of wild type and mutants of single-round infectious particles (SRIPs) and infectious clones (i.c.s) of ZIKV Asian-lineage Natal RGN strain, and then identified the function of amino acid substitutions at the positions 139 [Asn139\u2192Ser139 (N139S)] and 143 [Glu143\u2192Lys143 (E143K)] in ZIKV polyproteins (located within the pr region of prM protein) in the infectivity and cytopathogenicity. The E143K SRIP and i.c. of Natal RGN strain exhibited relatively higher levels of cytopathic effect, EGFP reporter, viral RNA and protein synthesis, and virus yield in three types of human cell lines, TE617, SF268 and HMC3, compared to wild type (WT), N139S SRIPs and i.c.s, which displayed more efficiency in replication kinetics. Additionally, E143K Natal RGN i.c. had greater activities of virus attachment and entry, yielded higher titers of intracellular and extracellular virions, and assembled the E proteins near to the plasma membrane in infected cells than the other i.c.s. The results indicate that the positively charged amino acid residue Lys143, a conserved residue in the pr region of prM of ZIKV African lineages, plays a crucial role in viral replication kinetics, including viral attachment, entry, assembly and egress. Thus, the negatively charged amino acid residue Glu143 within the pr region of prM leads to an alteration of the phenotypes, in particular, a lower replication efficiency of ZIKV Asian-lineage isolates with the attenuation of infectivity and cytopathicity.<\/jats:p>","DOI":"10.3390\/v14071572","type":"journal-article","created":{"date-parts":[[2022,7,22]],"date-time":"2022-07-22T03:58:44Z","timestamp":1658462324000},"page":"1572","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["A Reverse Mutation E143K within the PrM Protein of Zika Virus Asian Lineage Natal RGN Strain Increases Infectivity and Cytopathicity"],"prefix":"10.3390","volume":"14","author":[{"given":"Chen-Sheng","family":"Lin","sequence":"first","affiliation":[{"name":"Division of Gastroenterology, Kuang Tien General Hospital, No. 117, Shatian Rd, Shalu District, Taichung 433, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei-Jing","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Science and Biotechnology, China Medical University, No. 100, Sec. 1, Jingmao Rd., Beitun Dist., Taichung 404, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chih-Yi","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Science and Biotechnology, China Medical University, No. 100, Sec. 1, Jingmao Rd., Beitun Dist., Taichung 404, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ju-Ying","family":"Kan","sequence":"additional","affiliation":[{"name":"The PhD Program of Biotechnology and Biomedical Industry, China Medical University, No. 100, Sec. 1, Jingmao Rd., Beitun Dist., Taichung 404, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Szu-Hao","family":"Kung","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Laboratory Science in Medicine, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Su-Hua","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Science and Biotechnology, Asia University, No. 500, Lioufeng Rd., Wufeng, Taichung 41354, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hsueh-Chou","family":"Lai","sequence":"additional","affiliation":[{"name":"Division of Hepato-Gastroenterology, Department of Internal Medicine, China Medical University Hospital, No. 2, Yude Rd., North Dist., Taichung 404, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0165-2652","authenticated-orcid":false,"given":"Cheng-Wen","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Science and Biotechnology, China Medical University, No. 100, Sec. 1, Jingmao Rd., Beitun Dist., Taichung 404, Taiwan"},{"name":"The PhD Program of Biotechnology and Biomedical Industry, China Medical University, No. 100, Sec. 1, Jingmao Rd., Beitun Dist., Taichung 404, Taiwan"},{"name":"Department of Medical Laboratory Science and Biotechnology, Asia University, No. 500, Lioufeng Rd., Wufeng, Taichung 41354, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2099","DOI":"10.1016\/S0140-6736(17)31450-2","article-title":"An update on Zika virus infection","volume":"390","author":"Baud","year":"2017","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2940","DOI":"10.1093\/gbe\/evx223","article-title":"The Diversification of Zika Virus: Are There Two Distinct Lineages?","volume":"9","author":"Gong","year":"2017","journal-title":"Genome Biol. 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