Cargando…

Tolerance of Senecavirus A to Mutations in Its Kissing-Loop or Pseudoknot Structure Computationally Predicted in 3′ Untranslated Region

Senecavirus A (SVA) is an emerging virus that belongs to the genus Senecavirus in the family Picornaviridae. Its genome is a positive-sense and single-stranded RNA, containing two untranslated regions (UTRs). The 68-nt-long 3′ UTR is computationally predicted to possess two higher-order RNA structur...

Descripción completa

Detalles Bibliográficos
Autores principales: Liu, Fuxiao, Zhao, Di, Wang, Ning, Li, Ziwei, Dong, Yaqin, Liu, Shuang, Zhang, Feng, Cui, Jin, Meng, Hailan, Ni, Bo, Wei, Rong, Shan, Hu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9189406/
https://www.ncbi.nlm.nih.gov/pubmed/35707163
http://dx.doi.org/10.3389/fmicb.2022.889480
_version_ 1784725581827407872
author Liu, Fuxiao
Zhao, Di
Wang, Ning
Li, Ziwei
Dong, Yaqin
Liu, Shuang
Zhang, Feng
Cui, Jin
Meng, Hailan
Ni, Bo
Wei, Rong
Shan, Hu
author_facet Liu, Fuxiao
Zhao, Di
Wang, Ning
Li, Ziwei
Dong, Yaqin
Liu, Shuang
Zhang, Feng
Cui, Jin
Meng, Hailan
Ni, Bo
Wei, Rong
Shan, Hu
author_sort Liu, Fuxiao
collection PubMed
description Senecavirus A (SVA) is an emerging virus that belongs to the genus Senecavirus in the family Picornaviridae. Its genome is a positive-sense and single-stranded RNA, containing two untranslated regions (UTRs). The 68-nt-long 3′ UTR is computationally predicted to possess two higher-order RNA structures: a kissing-loop interaction and an H-type-like pseudoknot, both of which, however, cannot coexist in the 3′ UTR. In this study, we constructed 17 full-length SVA cDNA clones (cD-1 to -17): the cD-1 to -7 contained different point mutations in a kissing-loop-forming motif (KLFM); the cD-8 to -17 harbored one single or multiple point mutations in a pseudoknot-forming motif (PFM). These 17 mutated cDNA clones were independently transfected into BSR-T7/5 cells for rescuing recombinant SVAs (rSVAs), named rSVA-1 to −17, corresponding to cD-1 to −17. The results showed that the rSVA-1, -2, -3, -4, -5, -6, -7, -9, -13, and -15 were successfully rescued from their individual cDNA clones. Moreover, all mutated motifs were genetically stable during 10 viral passages in vitro. This study unveiled viral abilities of tolerating mutations in the computationally predicted KLFM or PFMs. It can be concluded that the putative kissing-loop structure, even if present in the 3′ UTR, is unnecessary for SVA replication. Alternatively, if the pseudoknot formation potentially occurs in the 3′ UTR, its deformation would have a lethal effect on SVA propagation.
format Online
Article
Text
id pubmed-9189406
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-91894062022-06-14 Tolerance of Senecavirus A to Mutations in Its Kissing-Loop or Pseudoknot Structure Computationally Predicted in 3′ Untranslated Region Liu, Fuxiao Zhao, Di Wang, Ning Li, Ziwei Dong, Yaqin Liu, Shuang Zhang, Feng Cui, Jin Meng, Hailan Ni, Bo Wei, Rong Shan, Hu Front Microbiol Microbiology Senecavirus A (SVA) is an emerging virus that belongs to the genus Senecavirus in the family Picornaviridae. Its genome is a positive-sense and single-stranded RNA, containing two untranslated regions (UTRs). The 68-nt-long 3′ UTR is computationally predicted to possess two higher-order RNA structures: a kissing-loop interaction and an H-type-like pseudoknot, both of which, however, cannot coexist in the 3′ UTR. In this study, we constructed 17 full-length SVA cDNA clones (cD-1 to -17): the cD-1 to -7 contained different point mutations in a kissing-loop-forming motif (KLFM); the cD-8 to -17 harbored one single or multiple point mutations in a pseudoknot-forming motif (PFM). These 17 mutated cDNA clones were independently transfected into BSR-T7/5 cells for rescuing recombinant SVAs (rSVAs), named rSVA-1 to −17, corresponding to cD-1 to −17. The results showed that the rSVA-1, -2, -3, -4, -5, -6, -7, -9, -13, and -15 were successfully rescued from their individual cDNA clones. Moreover, all mutated motifs were genetically stable during 10 viral passages in vitro. This study unveiled viral abilities of tolerating mutations in the computationally predicted KLFM or PFMs. It can be concluded that the putative kissing-loop structure, even if present in the 3′ UTR, is unnecessary for SVA replication. Alternatively, if the pseudoknot formation potentially occurs in the 3′ UTR, its deformation would have a lethal effect on SVA propagation. Frontiers Media S.A. 2022-05-30 /pmc/articles/PMC9189406/ /pubmed/35707163 http://dx.doi.org/10.3389/fmicb.2022.889480 Text en Copyright © 2022 Liu, Zhao, Wang, Li, Dong, Liu, Zhang, Cui, Meng, Ni, Wei and Shan. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Liu, Fuxiao
Zhao, Di
Wang, Ning
Li, Ziwei
Dong, Yaqin
Liu, Shuang
Zhang, Feng
Cui, Jin
Meng, Hailan
Ni, Bo
Wei, Rong
Shan, Hu
Tolerance of Senecavirus A to Mutations in Its Kissing-Loop or Pseudoknot Structure Computationally Predicted in 3′ Untranslated Region
title Tolerance of Senecavirus A to Mutations in Its Kissing-Loop or Pseudoknot Structure Computationally Predicted in 3′ Untranslated Region
title_full Tolerance of Senecavirus A to Mutations in Its Kissing-Loop or Pseudoknot Structure Computationally Predicted in 3′ Untranslated Region
title_fullStr Tolerance of Senecavirus A to Mutations in Its Kissing-Loop or Pseudoknot Structure Computationally Predicted in 3′ Untranslated Region
title_full_unstemmed Tolerance of Senecavirus A to Mutations in Its Kissing-Loop or Pseudoknot Structure Computationally Predicted in 3′ Untranslated Region
title_short Tolerance of Senecavirus A to Mutations in Its Kissing-Loop or Pseudoknot Structure Computationally Predicted in 3′ Untranslated Region
title_sort tolerance of senecavirus a to mutations in its kissing-loop or pseudoknot structure computationally predicted in 3′ untranslated region
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9189406/
https://www.ncbi.nlm.nih.gov/pubmed/35707163
http://dx.doi.org/10.3389/fmicb.2022.889480
work_keys_str_mv AT liufuxiao toleranceofsenecavirusatomutationsinitskissinglooporpseudoknotstructurecomputationallypredictedin3untranslatedregion
AT zhaodi toleranceofsenecavirusatomutationsinitskissinglooporpseudoknotstructurecomputationallypredictedin3untranslatedregion
AT wangning toleranceofsenecavirusatomutationsinitskissinglooporpseudoknotstructurecomputationallypredictedin3untranslatedregion
AT liziwei toleranceofsenecavirusatomutationsinitskissinglooporpseudoknotstructurecomputationallypredictedin3untranslatedregion
AT dongyaqin toleranceofsenecavirusatomutationsinitskissinglooporpseudoknotstructurecomputationallypredictedin3untranslatedregion
AT liushuang toleranceofsenecavirusatomutationsinitskissinglooporpseudoknotstructurecomputationallypredictedin3untranslatedregion
AT zhangfeng toleranceofsenecavirusatomutationsinitskissinglooporpseudoknotstructurecomputationallypredictedin3untranslatedregion
AT cuijin toleranceofsenecavirusatomutationsinitskissinglooporpseudoknotstructurecomputationallypredictedin3untranslatedregion
AT menghailan toleranceofsenecavirusatomutationsinitskissinglooporpseudoknotstructurecomputationallypredictedin3untranslatedregion
AT nibo toleranceofsenecavirusatomutationsinitskissinglooporpseudoknotstructurecomputationallypredictedin3untranslatedregion
AT weirong toleranceofsenecavirusatomutationsinitskissinglooporpseudoknotstructurecomputationallypredictedin3untranslatedregion
AT shanhu toleranceofsenecavirusatomutationsinitskissinglooporpseudoknotstructurecomputationallypredictedin3untranslatedregion