Leu-to-Phe substitution at prM146 decreases the growth ability of Zika virus and partially reduces its pathogenicity in mice

Abstract Zika virus (ZIKV) is a mosquito-borne flavivirus that causes febrile illness. The recent spread of ZIKV from Asia to the Americas via the Pacific region has revealed unprecedented features of ZIKV, including transplacental congenital infection causing microcephaly. Amino acid changes have b...

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Autores principales:	Takuya Inagaki, Satoshi Taniguchi, Yasuhiro Kawai, Takahiro Maeki, Eri Nakayama, Shigeru Tajima, Haruko Takeyama, Chang Kweng Lim, Masayuki Saijo
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/09300819fd214340ae09e4b3ec6fa69e
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spelling	oai:doaj.org-article:09300819fd214340ae09e4b3ec6fa69e2021-12-02T19:16:11ZLeu-to-Phe substitution at prM146 decreases the growth ability of Zika virus and partially reduces its pathogenicity in mice10.1038/s41598-021-99086-22045-2322https://doaj.org/article/09300819fd214340ae09e4b3ec6fa69e2021-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-99086-2https://doaj.org/toc/2045-2322Abstract Zika virus (ZIKV) is a mosquito-borne flavivirus that causes febrile illness. The recent spread of ZIKV from Asia to the Americas via the Pacific region has revealed unprecedented features of ZIKV, including transplacental congenital infection causing microcephaly. Amino acid changes have been hypothesized to underlie the spread and novel features of American ZIKV strains; however, the relationship between genetic changes and the epidemic remains controversial. A comparison of the characteristics of a Southeast Asian strain (NIID123) and an American strain (PRVABC59) revealed that the latter had a higher replication ability in cultured cells and higher virulence in mice. In this study, we aimed to identify the genetic region of ZIKV responsible for these different characteristics using reverse genetics. A chimeric NIID123 strain in which the E protein was replaced with that of PRVABC59 showed a lower growth ability than the recombinant wild-type strain. Adaptation of the chimeric NIID123 to Vero cells induced a Phe-to-Leu amino acid substitution at position 146 of the prM protein; PRVABC59 also has Leu at this position. Leu at this position was found to be responsible for the viral replication ability and partially, for the pathogenicity in mouse testes.Takuya InagakiSatoshi TaniguchiYasuhiro KawaiTakahiro MaekiEri NakayamaShigeru TajimaHaruko TakeyamaChang Kweng LimMasayuki SaijoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Takuya Inagaki Satoshi Taniguchi Yasuhiro Kawai Takahiro Maeki Eri Nakayama Shigeru Tajima Haruko Takeyama Chang Kweng Lim Masayuki Saijo Leu-to-Phe substitution at prM146 decreases the growth ability of Zika virus and partially reduces its pathogenicity in mice
description	Abstract Zika virus (ZIKV) is a mosquito-borne flavivirus that causes febrile illness. The recent spread of ZIKV from Asia to the Americas via the Pacific region has revealed unprecedented features of ZIKV, including transplacental congenital infection causing microcephaly. Amino acid changes have been hypothesized to underlie the spread and novel features of American ZIKV strains; however, the relationship between genetic changes and the epidemic remains controversial. A comparison of the characteristics of a Southeast Asian strain (NIID123) and an American strain (PRVABC59) revealed that the latter had a higher replication ability in cultured cells and higher virulence in mice. In this study, we aimed to identify the genetic region of ZIKV responsible for these different characteristics using reverse genetics. A chimeric NIID123 strain in which the E protein was replaced with that of PRVABC59 showed a lower growth ability than the recombinant wild-type strain. Adaptation of the chimeric NIID123 to Vero cells induced a Phe-to-Leu amino acid substitution at position 146 of the prM protein; PRVABC59 also has Leu at this position. Leu at this position was found to be responsible for the viral replication ability and partially, for the pathogenicity in mouse testes.
format	article
author	Takuya Inagaki Satoshi Taniguchi Yasuhiro Kawai Takahiro Maeki Eri Nakayama Shigeru Tajima Haruko Takeyama Chang Kweng Lim Masayuki Saijo
author_facet	Takuya Inagaki Satoshi Taniguchi Yasuhiro Kawai Takahiro Maeki Eri Nakayama Shigeru Tajima Haruko Takeyama Chang Kweng Lim Masayuki Saijo
author_sort	Takuya Inagaki
title	Leu-to-Phe substitution at prM146 decreases the growth ability of Zika virus and partially reduces its pathogenicity in mice
title_short	Leu-to-Phe substitution at prM146 decreases the growth ability of Zika virus and partially reduces its pathogenicity in mice
title_full	Leu-to-Phe substitution at prM146 decreases the growth ability of Zika virus and partially reduces its pathogenicity in mice
title_fullStr	Leu-to-Phe substitution at prM146 decreases the growth ability of Zika virus and partially reduces its pathogenicity in mice
title_full_unstemmed	Leu-to-Phe substitution at prM146 decreases the growth ability of Zika virus and partially reduces its pathogenicity in mice
title_sort	leu-to-phe substitution at prm146 decreases the growth ability of zika virus and partially reduces its pathogenicity in mice
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/09300819fd214340ae09e4b3ec6fa69e
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Leu-to-Phe substitution at prM146 decreases the growth ability of Zika virus and partially reduces its pathogenicity in mice

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