Rabies Virus Populations in Humans and Mice Show Minor Inter-Host Variability within Various Central Nervous System Regions and Peripheral Tissues

Rabies virus (RABV) has a broad host range and infects multiple cell types throughout the infection cycle. Next-generation sequencing (NGS) and minor variant analysis are powerful tools for studying virus populations within specific hosts and tissues, leading to novel insights into the mechanisms of...

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Main Authors: Carmen W. E. Embregts, Elmoubashar A. B. A. Farag, Devendra Bansal, Marjan Boter, Anne van der Linden, Vincent P. Vaes, Ingeborg van Middelkoop-van den Berg, Jeroen. IJpelaar, Hisham Ziglam, Peter V. Coyle, Imad Ibrahim, Khaled A. Mohran, Muneera Mohammed Saleh Alrajhi, Md. Mazharul Islam, Randa Abdeen, Abdul Aziz Al-Zeyara, Nidal Mahmoud Younis, Hamad Eid Al-Romaihi, Mohammad Hamad J. AlThani, Reina S. Sikkema, Marion P. G. Koopmans, Bas B. Oude Munnink, Corine H. GeurtsvanKessel
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Language:English
Published: MDPI AG 2022-11-01
Series:Viruses
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Online Access:https://www.mdpi.com/1999-4915/14/12/2661
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author Carmen W. E. Embregts
Elmoubashar A. B. A. Farag
Devendra Bansal
Marjan Boter
Anne van der Linden
Vincent P. Vaes
Ingeborg van Middelkoop-van den Berg
Jeroen. IJpelaar
Hisham Ziglam
Peter V. Coyle
Imad Ibrahim
Khaled A. Mohran
Muneera Mohammed Saleh Alrajhi
Md. Mazharul Islam
Randa Abdeen
Abdul Aziz Al-Zeyara
Nidal Mahmoud Younis
Hamad Eid Al-Romaihi
Mohammad Hamad J. AlThani
Reina S. Sikkema
Marion P. G. Koopmans
Bas B. Oude Munnink
Corine H. GeurtsvanKessel
author_facet Carmen W. E. Embregts
Elmoubashar A. B. A. Farag
Devendra Bansal
Marjan Boter
Anne van der Linden
Vincent P. Vaes
Ingeborg van Middelkoop-van den Berg
Jeroen. IJpelaar
Hisham Ziglam
Peter V. Coyle
Imad Ibrahim
Khaled A. Mohran
Muneera Mohammed Saleh Alrajhi
Md. Mazharul Islam
Randa Abdeen
Abdul Aziz Al-Zeyara
Nidal Mahmoud Younis
Hamad Eid Al-Romaihi
Mohammad Hamad J. AlThani
Reina S. Sikkema
Marion P. G. Koopmans
Bas B. Oude Munnink
Corine H. GeurtsvanKessel
author_sort Carmen W. E. Embregts
collection DOAJ
description Rabies virus (RABV) has a broad host range and infects multiple cell types throughout the infection cycle. Next-generation sequencing (NGS) and minor variant analysis are powerful tools for studying virus populations within specific hosts and tissues, leading to novel insights into the mechanisms of host-switching and key factors for infecting specific cell types. In this study we investigated RABV populations and minor variants in both original (non-passaged) samples and in vitro-passaged isolates of various CNS regions (hippocampus, medulla oblongata and spinal cord) of a fatal human rabies case, and of multiple CNS and non-CNS tissues of experimentally infected mice. No differences in virus populations were detected between the human CNS regions, and only one non-synonymous single nucleotide polymorphism (SNP) was detected in the fifth in vitro passage of virus isolated from the spinal cord. However, the appearance of this SNP shows the importance of sequencing newly passaged virus stocks before further use. Similarly, we did not detect apparent differences in virus populations isolated from different CNS and non-CNS tissues of experimentally infected mice. Sequencing of viruses obtained from pharyngeal swab and salivary gland proved difficult, and we propose methods for improving sampling.
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spelling doaj.art-41e54fea7bcc41a683f43c727af8dddd2023-11-24T18:37:24ZengMDPI AGViruses1999-49152022-11-011412266110.3390/v14122661Rabies Virus Populations in Humans and Mice Show Minor Inter-Host Variability within Various Central Nervous System Regions and Peripheral TissuesCarmen W. E. Embregts0Elmoubashar A. B. A. Farag1Devendra Bansal2Marjan Boter3Anne van der Linden4Vincent P. Vaes5Ingeborg van Middelkoop-van den Berg6Jeroen. IJpelaar7Hisham Ziglam8Peter V. Coyle9Imad Ibrahim10Khaled A. Mohran11Muneera Mohammed Saleh Alrajhi12Md. Mazharul Islam13Randa Abdeen14Abdul Aziz Al-Zeyara15Nidal Mahmoud Younis16Hamad Eid Al-Romaihi17Mohammad Hamad J. AlThani18Reina S. Sikkema19Marion P. G. Koopmans20Bas B. Oude Munnink21Corine H. GeurtsvanKessel22Department of Viroscience, Erasmus Medical Centre, 3015 GD Rotterdam, The NetherlandsMinistry of Public Health, Doha P.O. Box 42, QatarMinistry of Public Health, Doha P.O. Box 42, QatarDepartment of Viroscience, Erasmus Medical Centre, 3015 GD Rotterdam, The NetherlandsDepartment of Viroscience, Erasmus Medical Centre, 3015 GD Rotterdam, The NetherlandsDepartment of Viroscience, Erasmus Medical Centre, 3015 GD Rotterdam, The NetherlandsDepartment of Viroscience, Erasmus Medical Centre, 3015 GD Rotterdam, The NetherlandsDepartment of Viroscience, Erasmus Medical Centre, 3015 GD Rotterdam, The NetherlandsHamad Medical Corporation, Doha P.O. Box 3050, QatarHamad Medical Corporation, Doha P.O. Box 3050, QatarHamad Medical Corporation, Doha P.O. Box 3050, QatarDepartment of Animal Resources, Ministry of Municipality, Doha P.O. Box 35081, QatarDepartment of Animal Resources, Ministry of Municipality, Doha P.O. Box 35081, QatarDepartment of Animal Resources, Ministry of Municipality, Doha P.O. Box 35081, QatarDepartment of Animal Resources, Ministry of Municipality, Doha P.O. Box 35081, QatarDepartment of Animal Resources, Ministry of Municipality, Doha P.O. Box 35081, QatarDepartment of Animal Resources, Ministry of Municipality, Doha P.O. Box 35081, QatarMinistry of Public Health, Doha P.O. Box 42, QatarMinistry of Public Health, Doha P.O. Box 42, QatarDepartment of Viroscience, Erasmus Medical Centre, 3015 GD Rotterdam, The NetherlandsDepartment of Viroscience, Erasmus Medical Centre, 3015 GD Rotterdam, The NetherlandsDepartment of Viroscience, Erasmus Medical Centre, 3015 GD Rotterdam, The NetherlandsDepartment of Viroscience, Erasmus Medical Centre, 3015 GD Rotterdam, The NetherlandsRabies virus (RABV) has a broad host range and infects multiple cell types throughout the infection cycle. Next-generation sequencing (NGS) and minor variant analysis are powerful tools for studying virus populations within specific hosts and tissues, leading to novel insights into the mechanisms of host-switching and key factors for infecting specific cell types. In this study we investigated RABV populations and minor variants in both original (non-passaged) samples and in vitro-passaged isolates of various CNS regions (hippocampus, medulla oblongata and spinal cord) of a fatal human rabies case, and of multiple CNS and non-CNS tissues of experimentally infected mice. No differences in virus populations were detected between the human CNS regions, and only one non-synonymous single nucleotide polymorphism (SNP) was detected in the fifth in vitro passage of virus isolated from the spinal cord. However, the appearance of this SNP shows the importance of sequencing newly passaged virus stocks before further use. Similarly, we did not detect apparent differences in virus populations isolated from different CNS and non-CNS tissues of experimentally infected mice. Sequencing of viruses obtained from pharyngeal swab and salivary gland proved difficult, and we propose methods for improving sampling.https://www.mdpi.com/1999-4915/14/12/2661rabies virusNGSminor variantsCNS
spellingShingle Carmen W. E. Embregts
Elmoubashar A. B. A. Farag
Devendra Bansal
Marjan Boter
Anne van der Linden
Vincent P. Vaes
Ingeborg van Middelkoop-van den Berg
Jeroen. IJpelaar
Hisham Ziglam
Peter V. Coyle
Imad Ibrahim
Khaled A. Mohran
Muneera Mohammed Saleh Alrajhi
Md. Mazharul Islam
Randa Abdeen
Abdul Aziz Al-Zeyara
Nidal Mahmoud Younis
Hamad Eid Al-Romaihi
Mohammad Hamad J. AlThani
Reina S. Sikkema
Marion P. G. Koopmans
Bas B. Oude Munnink
Corine H. GeurtsvanKessel
Rabies Virus Populations in Humans and Mice Show Minor Inter-Host Variability within Various Central Nervous System Regions and Peripheral Tissues
Viruses
rabies virus
NGS
minor variants
CNS
title Rabies Virus Populations in Humans and Mice Show Minor Inter-Host Variability within Various Central Nervous System Regions and Peripheral Tissues
title_full Rabies Virus Populations in Humans and Mice Show Minor Inter-Host Variability within Various Central Nervous System Regions and Peripheral Tissues
title_fullStr Rabies Virus Populations in Humans and Mice Show Minor Inter-Host Variability within Various Central Nervous System Regions and Peripheral Tissues
title_full_unstemmed Rabies Virus Populations in Humans and Mice Show Minor Inter-Host Variability within Various Central Nervous System Regions and Peripheral Tissues
title_short Rabies Virus Populations in Humans and Mice Show Minor Inter-Host Variability within Various Central Nervous System Regions and Peripheral Tissues
title_sort rabies virus populations in humans and mice show minor inter host variability within various central nervous system regions and peripheral tissues
topic rabies virus
NGS
minor variants
CNS
url https://www.mdpi.com/1999-4915/14/12/2661
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