TY - JOUR
T1 - Rabies Virus Populations in Humans and Mice Show Minor Inter-Host Variability within Various Central Nervous System Regions and Peripheral Tissues
AU - Embregts, Carmen W.E.
AU - Farag, Elmoubashar A.B.A.
AU - Bansal, Devendra
AU - Boter, Marjan
AU - van der Linden, Anne
AU - Vaes, Vincent P.
AU - van Middelkoop-van den Berg, Ingeborg
AU - IJpelaar, Jeroen
AU - Ziglam, Hisham
AU - Coyle, Peter V.
AU - Ibrahim, Imad
AU - Mohran, Khaled A.
AU - Alrajhi, Muneera Mohammed Saleh
AU - Islam, Md Mazharul
AU - Abdeen, Randa
AU - Al-Zeyara, Abdul Aziz
AU - Younis, Nidal Mahmoud
AU - Al-Romaihi, Hamad Eid
AU - AlThani, Mohammad Hamad J.
AU - Sikkema, Reina S.
AU - Koopmans, Marion P.G.
AU - Oude Munnink, Bas B.
AU - GeurtsvanKessel, Corine H.
N1 - 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.
PY - 2022/11/28
Y1 - 2022/11/28
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85144519050&partnerID=8YFLogxK
U2 - 10.3390/v14122661
DO - 10.3390/v14122661
M3 - Article
C2 - 36560665
AN - SCOPUS:85144519050
VL - 14
JO - Viruses
JF - Viruses
SN - 1999-4915
IS - 12
M1 - 2661
ER -
