Host-Specific Restriction of Avian Influenza Virus Caused by Differential Dynamics of ANP32 Family Members
Abstract Background Influenza viruses must utilize host factors to complete their lifecycle. Species-specific differences in host factors between birds and mammals mean that avian influenza viruses (AIVs) replicate well in avian hosts but not in human hosts. Acidic nuclear phosphoprotein 32 family m...
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Published in | The Journal of infectious diseases Vol. 221; no. 1; pp. 71 - 80 |
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Main Authors | , , , , , , , , , , |
Format | Journal Article |
Language | English |
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Oxford University Press
01.01.2020
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Abstract | Abstract
Background
Influenza viruses must utilize host factors to complete their lifecycle. Species-specific differences in host factors between birds and mammals mean that avian influenza viruses (AIVs) replicate well in avian hosts but not in human hosts. Acidic nuclear phosphoprotein 32 family member A (ANP32A) has been identified as the host restriction factor for the viral polymerase (vPol) activity of AIVs. The ANP32A belongs to the conserved ANP32 family, the functional roles of which during viral replication remain unclear.
Methods
In this study, we targeted chicken ANP32A using clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-mediated genome editing to examine the functional roles of ANP32A and other members of the ANP32 family.
Results
We showed that chicken ANP32A only, not ANP32B and ANP32E, plays a pivotal role in supporting vPol activity of AIVs. Furthermore, we found that the human ANP32C, ANP32D, and ANP32E have suppressive effects on vPol activity in contrast to human ANP32A and ANP32B.
Conclusions
Chicken and human ANP32 family members had different effects on vPol activity, suggesting that species-specific vPol activity of AIVs could be caused by the differential functions and overall competency of ANP32 family members.
Genetic differences in ANP32A between chicken and humans and the differential effects of ANP32 family members on influenza virus replication could result in PB2-627 residue-dependent host restriction. |
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AbstractList | Abstract
Background
Influenza viruses must utilize host factors to complete their lifecycle. Species-specific differences in host factors between birds and mammals mean that avian influenza viruses (AIVs) replicate well in avian hosts but not in human hosts. Acidic nuclear phosphoprotein 32 family member A (ANP32A) has been identified as the host restriction factor for the viral polymerase (vPol) activity of AIVs. The ANP32A belongs to the conserved ANP32 family, the functional roles of which during viral replication remain unclear.
Methods
In this study, we targeted chicken ANP32A using clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-mediated genome editing to examine the functional roles of ANP32A and other members of the ANP32 family.
Results
We showed that chicken ANP32A only, not ANP32B and ANP32E, plays a pivotal role in supporting vPol activity of AIVs. Furthermore, we found that the human ANP32C, ANP32D, and ANP32E have suppressive effects on vPol activity in contrast to human ANP32A and ANP32B.
Conclusions
Chicken and human ANP32 family members had different effects on vPol activity, suggesting that species-specific vPol activity of AIVs could be caused by the differential functions and overall competency of ANP32 family members.
Genetic differences in ANP32A between chicken and humans and the differential effects of ANP32 family members on influenza virus replication could result in PB2-627 residue-dependent host restriction. Background Influenza viruses must utilize host factors to complete their lifecycle. Species-specific differences in host factors between birds and mammals mean that avian influenza viruses (AIVs) replicate well in avian hosts but not in human hosts. Acidic nuclear phosphoprotein 32 family member A (ANP32A) has been identified as the host restriction factor for the viral polymerase (vPol) activity of AIVs. The ANP32A belongs to the conserved ANP32 family, the functional roles of which during viral replication remain unclear. Methods In this study, we targeted chicken ANP32A using clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-mediated genome editing to examine the functional roles of ANP32A and other members of the ANP32 family. Results We showed that chicken ANP32A only, not ANP32B and ANP32E, plays a pivotal role in supporting vPol activity of AIVs. Furthermore, we found that the human ANP32C, ANP32D, and ANP32E have suppressive effects on vPol activity in contrast to human ANP32A and ANP32B. Conclusions Chicken and human ANP32 family members had different effects on vPol activity, suggesting that species-specific vPol activity of AIVs could be caused by the differential functions and overall competency of ANP32 family members. Abstract Background Influenza viruses must utilize host factors to complete their lifecycle. Species-specific differences in host factors between birds and mammals mean that avian influenza viruses (AIVs) replicate well in avian hosts but not in human hosts. Acidic nuclear phosphoprotein 32 family member A (ANP32A) has been identified as the host restriction factor for the viral polymerase (vPol) activity of AIVs. The ANP32A belongs to the conserved ANP32 family, the functional roles of which during viral replication remain unclear. Methods In this study, we targeted chicken ANP32A using clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-mediated genome editing to examine the functional roles of ANP32A and other members of the ANP32 family. Results We showed that chicken ANP32A only, not ANP32B and ANP32E, plays a pivotal role in supporting vPol activity of AIVs. Furthermore, we found that the human ANP32C, ANP32D, and ANP32E have suppressive effects on vPol activity in contrast to human ANP32A and ANP32B. Conclusions Chicken and human ANP32 family members had different effects on vPol activity, suggesting that species-specific vPol activity of AIVs could be caused by the differential functions and overall competency of ANP32 family members. BACKGROUNDInfluenza viruses must utilize host factors to complete their lifecycle. Species-specific differences in host factors between birds and mammals mean that avian influenza viruses (AIVs) replicate well in avian hosts but not in human hosts. Acidic nuclear phosphoprotein 32 family member A (ANP32A) has been identified as the host restriction factor for the viral polymerase (vPol) activity of AIVs. The ANP32A belongs to the conserved ANP32 family, the functional roles of which during viral replication remain unclear. METHODSIn this study, we targeted chicken ANP32A using clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-mediated genome editing to examine the functional roles of ANP32A and other members of the ANP32 family. RESULTSWe showed that chicken ANP32A only, not ANP32B and ANP32E, plays a pivotal role in supporting vPol activity of AIVs. Furthermore, we found that the human ANP32C, ANP32D, and ANP32E have suppressive effects on vPol activity in contrast to human ANP32A and ANP32B. CONCLUSIONSChicken and human ANP32 family members had different effects on vPol activity, suggesting that species-specific vPol activity of AIVs could be caused by the differential functions and overall competency of ANP32 family members. |
Author | Rengaraj, Deivendran Lee, Ji-Ho Park, Young Hyun Lee, Hong Jo Chungu, Kelly Lee, Su Bin Song, Chang-Seon Cho, Ho Yeon Woo, Seung Je Lim, Jeong Mook Han, Jae Yong |
Author_xml | – sequence: 1 givenname: Young Hyun surname: Park fullname: Park, Young Hyun organization: Department of Agricultural Biotechnology and Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul, Republic of Korea – sequence: 2 givenname: Kelly surname: Chungu fullname: Chungu, Kelly organization: Department of Agricultural Biotechnology and Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul, Republic of Korea – sequence: 3 givenname: Su Bin surname: Lee fullname: Lee, Su Bin organization: Department of Agricultural Biotechnology and Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul, Republic of Korea – sequence: 4 givenname: Seung Je surname: Woo fullname: Woo, Seung Je organization: Department of Agricultural Biotechnology and Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul, Republic of Korea – sequence: 5 givenname: Ho Yeon surname: Cho fullname: Cho, Ho Yeon organization: Department of Agricultural Biotechnology and Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul, Republic of Korea – sequence: 6 givenname: Hong Jo surname: Lee fullname: Lee, Hong Jo organization: Department of Agricultural Biotechnology and Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul, Republic of Korea – sequence: 7 givenname: Deivendran surname: Rengaraj fullname: Rengaraj, Deivendran organization: Department of Agricultural Biotechnology and Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul, Republic of Korea – sequence: 8 givenname: Ji-Ho surname: Lee fullname: Lee, Ji-Ho organization: Avian Diseases Laboratory, College of Veterinary Medicine, Konkuk University, Seoul, Republic of Korea – sequence: 9 givenname: Chang-Seon surname: Song fullname: Song, Chang-Seon organization: Avian Diseases Laboratory, College of Veterinary Medicine, Konkuk University, Seoul, Republic of Korea – sequence: 10 givenname: Jeong Mook surname: Lim fullname: Lim, Jeong Mook organization: Department of Agricultural Biotechnology and Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul, Republic of Korea – sequence: 11 givenname: Jae Yong orcidid: 0000-0003-3413-3277 surname: Han fullname: Han, Jae Yong email: jaehan@snu.ac.kr organization: Department of Agricultural Biotechnology and Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul, Republic of Korea |
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Copyright_xml | – notice: The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com. 2019 – notice: The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com. |
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Background
Influenza viruses must utilize host factors to complete their lifecycle. Species-specific differences in host factors between birds and... Background Influenza viruses must utilize host factors to complete their lifecycle. Species-specific differences in host factors between birds and mammals mean... BACKGROUNDInfluenza viruses must utilize host factors to complete their lifecycle. Species-specific differences in host factors between birds and mammals mean... |
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SubjectTerms | Avian flu CRISPR Genome editing Genomes Influenza |
Title | Host-Specific Restriction of Avian Influenza Virus Caused by Differential Dynamics of ANP32 Family Members |
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