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

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. SikkemaMarion P.G. Koopmans, Bas B. Oude Munnink, Corine H. GeurtsvanKessel

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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.

Original languageEnglish
Article number2661
JournalViruses
Volume14
Issue number12
DOIs
Publication statusPublished - 28 Nov 2022

Bibliographical note

Funding Information:
This work was funded through an Erasmus MC Fellowship 2019, project number 110581. CE is funded by a VENI Grant from The Netherlands Organization for Scientific Research (NWO-VENI 09150162010181).

Publisher Copyright:
© 2022 by the authors.

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