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SMRT sequencing revealed the diversity and characteristics of defective interfering RNAs in influenza A (H7N9) virus infection
Influenza defective interfering (DI) particles are replication-incompetent viruses carrying large internal deletion in the genome. The loss of essential genetic information causes abortive viral replication, which can be rescued by co-infection with a helper virus that possesses an intact genome. De...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6534226/ https://www.ncbi.nlm.nih.gov/pubmed/31084471 http://dx.doi.org/10.1080/22221751.2019.1611346 |
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author | Lui, Wing-Yu Yuen, Chun-Kit Li, Can Wong, Wan Man Lui, Pak-Yin Lin, Chi-Ho Chan, Kwok-Hung Zhao, Hanjun Chen, Honglin To, Kelvin K. W. Zhang, Anna J. X Yuen, Kwok-Yung Kok, Kin-Hang |
author_facet | Lui, Wing-Yu Yuen, Chun-Kit Li, Can Wong, Wan Man Lui, Pak-Yin Lin, Chi-Ho Chan, Kwok-Hung Zhao, Hanjun Chen, Honglin To, Kelvin K. W. Zhang, Anna J. X Yuen, Kwok-Yung Kok, Kin-Hang |
author_sort | Lui, Wing-Yu |
collection | PubMed |
description | Influenza defective interfering (DI) particles are replication-incompetent viruses carrying large internal deletion in the genome. The loss of essential genetic information causes abortive viral replication, which can be rescued by co-infection with a helper virus that possesses an intact genome. Despite reports of DI particles present in seasonal influenza A H1N1 infections, their existence in human infections by the avian influenza A viruses, such as H7N9, has not been studied. Here we report the ubiquitous presence of DI-RNAs in nasopharyngeal aspirates of H7N9-infected patients. Single Molecule Real Time (SMRT) sequencing was first applied and long-read sequencing analysis showed that a variety of H7N9 DI-RNA species were present in the patient samples and human bronchial epithelial cells. In several abundantly expressed DI-RNA species, long overlapping sequences have been identified around at the breakpoint region and the other side of deleted region. Influenza DI-RNA is known as a defective viral RNA with single large internal deletion. Beneficial to the long-read property of SMRT sequencing, double and triple internal deletions were identified in half of the DI-RNA species. In addition, we examined the expression of DI-RNAs in mice infected with sublethal dose of H7N9 virus at different time points. Interestingly, DI-RNAs were abundantly expressed as early as day 2 post-infection. Taken together, we reveal the diversity and characteristics of DI-RNAs found in H7N9-infected patients, cells and animals. Further investigations on this overwhelming generation of DI-RNA may provide important insights into the understanding of H7N9 viral replication and pathogenesis. |
format | Online Article Text |
id | pubmed-6534226 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-65342262019-06-12 SMRT sequencing revealed the diversity and characteristics of defective interfering RNAs in influenza A (H7N9) virus infection Lui, Wing-Yu Yuen, Chun-Kit Li, Can Wong, Wan Man Lui, Pak-Yin Lin, Chi-Ho Chan, Kwok-Hung Zhao, Hanjun Chen, Honglin To, Kelvin K. W. Zhang, Anna J. X Yuen, Kwok-Yung Kok, Kin-Hang Emerg Microbes Infect Original Articles Influenza defective interfering (DI) particles are replication-incompetent viruses carrying large internal deletion in the genome. The loss of essential genetic information causes abortive viral replication, which can be rescued by co-infection with a helper virus that possesses an intact genome. Despite reports of DI particles present in seasonal influenza A H1N1 infections, their existence in human infections by the avian influenza A viruses, such as H7N9, has not been studied. Here we report the ubiquitous presence of DI-RNAs in nasopharyngeal aspirates of H7N9-infected patients. Single Molecule Real Time (SMRT) sequencing was first applied and long-read sequencing analysis showed that a variety of H7N9 DI-RNA species were present in the patient samples and human bronchial epithelial cells. In several abundantly expressed DI-RNA species, long overlapping sequences have been identified around at the breakpoint region and the other side of deleted region. Influenza DI-RNA is known as a defective viral RNA with single large internal deletion. Beneficial to the long-read property of SMRT sequencing, double and triple internal deletions were identified in half of the DI-RNA species. In addition, we examined the expression of DI-RNAs in mice infected with sublethal dose of H7N9 virus at different time points. Interestingly, DI-RNAs were abundantly expressed as early as day 2 post-infection. Taken together, we reveal the diversity and characteristics of DI-RNAs found in H7N9-infected patients, cells and animals. Further investigations on this overwhelming generation of DI-RNA may provide important insights into the understanding of H7N9 viral replication and pathogenesis. Taylor & Francis 2019-05-14 /pmc/articles/PMC6534226/ /pubmed/31084471 http://dx.doi.org/10.1080/22221751.2019.1611346 Text en © 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group on behalf of Shanghai Shangyixun Cultural Communication Co., Ltd http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Lui, Wing-Yu Yuen, Chun-Kit Li, Can Wong, Wan Man Lui, Pak-Yin Lin, Chi-Ho Chan, Kwok-Hung Zhao, Hanjun Chen, Honglin To, Kelvin K. W. Zhang, Anna J. X Yuen, Kwok-Yung Kok, Kin-Hang SMRT sequencing revealed the diversity and characteristics of defective interfering RNAs in influenza A (H7N9) virus infection |
title | SMRT sequencing revealed the diversity and characteristics of defective interfering RNAs in influenza A (H7N9) virus infection |
title_full | SMRT sequencing revealed the diversity and characteristics of defective interfering RNAs in influenza A (H7N9) virus infection |
title_fullStr | SMRT sequencing revealed the diversity and characteristics of defective interfering RNAs in influenza A (H7N9) virus infection |
title_full_unstemmed | SMRT sequencing revealed the diversity and characteristics of defective interfering RNAs in influenza A (H7N9) virus infection |
title_short | SMRT sequencing revealed the diversity and characteristics of defective interfering RNAs in influenza A (H7N9) virus infection |
title_sort | smrt sequencing revealed the diversity and characteristics of defective interfering rnas in influenza a (h7n9) virus infection |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6534226/ https://www.ncbi.nlm.nih.gov/pubmed/31084471 http://dx.doi.org/10.1080/22221751.2019.1611346 |
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