Inoculation route-dependent Lassa virus dissemination and shedding dynamics in the natural reservoir – Mastomys natalensis

Lassa virus (LASV), a Risk Group-4 zoonotic haemorrhagic fever virus, affects sub-Saharan African countries. Lassa fever, caused by LASV, results in thousands of annual deaths. Although decades have elapsed since the identification of the Natal multimammate mouse (Mastomys natalensis) as a natural r...

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Main Authors: D. M. Wozniak, S. A. Riesle-Sbarbaro, N. Kirchoff, K. Hansen-Kant, A. Wahlbrink, A. Stern, A. Lander, K. Hartmann, S. Krasemann, A. Kurth, J. Prescott
Format: Article
Language:English
Published: Taylor & Francis Group 2021-01-01
Series:Emerging Microbes and Infections
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Online Access:https://www.tandfonline.com/doi/10.1080/22221751.2021.2008773
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author D. M. Wozniak
S. A. Riesle-Sbarbaro
N. Kirchoff
K. Hansen-Kant
A. Wahlbrink
A. Stern
A. Lander
K. Hartmann
S. Krasemann
A. Kurth
J. Prescott
author_facet D. M. Wozniak
S. A. Riesle-Sbarbaro
N. Kirchoff
K. Hansen-Kant
A. Wahlbrink
A. Stern
A. Lander
K. Hartmann
S. Krasemann
A. Kurth
J. Prescott
author_sort D. M. Wozniak
collection DOAJ
description Lassa virus (LASV), a Risk Group-4 zoonotic haemorrhagic fever virus, affects sub-Saharan African countries. Lassa fever, caused by LASV, results in thousands of annual deaths. Although decades have elapsed since the identification of the Natal multimammate mouse (Mastomys natalensis) as a natural reservoir of LASV, little effort has been made to characterize LASV infection in its reservoir. The natural route of infection and transmission of LASV within M. natalensis remains unknown, and the clinical impact of LASV in M. natalensis is mostly undescribed. Herein, using an outbred colony of M. natalensis, we investigate the replication and dissemination dynamics of LASV in this reservoir following various inoculation routes. Inoculation with LASV, regardless of route, resulted in a systemic infection and accumulation of abundant LASV-RNA in many tissues. LASV infection in the Natal multimammate mice was subclinical, however, clinical chemistry values were transiently altered and immune infiltrates were observed histologically in lungs, spleens and livers, indicating a minor disease with coordinated immune responses are elicited, controlling infection. Intranasal infection resulted in unique virus tissue dissemination dynamics and heightened LASV shedding, compared to subcutaneous inoculation. Our study provides important insights into LASV infection in its natural reservoir using a contemporary infection system, demonstrating that specific inoculation routes result in disparate dissemination outcomes, suggesting intranasal inoculation is important in the maintenance of LASV in the natural reservoir, and emphasizes that selection of the appropriate inoculation route is necessary to examine aspects of viral replication, transmission and responses to zoonotic viruses in their natural reservoirs.
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spelling doaj-art-0ff16b2e47e54e118abc44d583c491972025-08-20T03:52:56ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512021-01-011012313232510.1080/22221751.2021.2008773Inoculation route-dependent Lassa virus dissemination and shedding dynamics in the natural reservoir – Mastomys natalensisD. M. Wozniak0S. A. Riesle-Sbarbaro1N. Kirchoff2K. Hansen-Kant3A. Wahlbrink4A. Stern5A. Lander6K. Hartmann7S. Krasemann8A. Kurth9J. Prescott10ZBS5—Biosafety Level-4 Laboratory, Robert Koch-Institute, Berlin, GermanyZBS5—Biosafety Level-4 Laboratory, Robert Koch-Institute, Berlin, GermanyZBS5—Biosafety Level-4 Laboratory, Robert Koch-Institute, Berlin, GermanyZBS5—Biosafety Level-4 Laboratory, Robert Koch-Institute, Berlin, GermanyZBS5—Biosafety Level-4 Laboratory, Robert Koch-Institute, Berlin, GermanyZBS5—Biosafety Level-4 Laboratory, Robert Koch-Institute, Berlin, GermanyZBS5—Biosafety Level-4 Laboratory, Robert Koch-Institute, Berlin, GermanyInstitute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyInstitute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyZBS5—Biosafety Level-4 Laboratory, Robert Koch-Institute, Berlin, GermanyZBS5—Biosafety Level-4 Laboratory, Robert Koch-Institute, Berlin, GermanyLassa virus (LASV), a Risk Group-4 zoonotic haemorrhagic fever virus, affects sub-Saharan African countries. Lassa fever, caused by LASV, results in thousands of annual deaths. Although decades have elapsed since the identification of the Natal multimammate mouse (Mastomys natalensis) as a natural reservoir of LASV, little effort has been made to characterize LASV infection in its reservoir. The natural route of infection and transmission of LASV within M. natalensis remains unknown, and the clinical impact of LASV in M. natalensis is mostly undescribed. Herein, using an outbred colony of M. natalensis, we investigate the replication and dissemination dynamics of LASV in this reservoir following various inoculation routes. Inoculation with LASV, regardless of route, resulted in a systemic infection and accumulation of abundant LASV-RNA in many tissues. LASV infection in the Natal multimammate mice was subclinical, however, clinical chemistry values were transiently altered and immune infiltrates were observed histologically in lungs, spleens and livers, indicating a minor disease with coordinated immune responses are elicited, controlling infection. Intranasal infection resulted in unique virus tissue dissemination dynamics and heightened LASV shedding, compared to subcutaneous inoculation. Our study provides important insights into LASV infection in its natural reservoir using a contemporary infection system, demonstrating that specific inoculation routes result in disparate dissemination outcomes, suggesting intranasal inoculation is important in the maintenance of LASV in the natural reservoir, and emphasizes that selection of the appropriate inoculation route is necessary to examine aspects of viral replication, transmission and responses to zoonotic viruses in their natural reservoirs.https://www.tandfonline.com/doi/10.1080/22221751.2021.2008773Lassa virusLASVMastomys natalensisdisseminationsheddingnatural reservoir
spellingShingle D. M. Wozniak
S. A. Riesle-Sbarbaro
N. Kirchoff
K. Hansen-Kant
A. Wahlbrink
A. Stern
A. Lander
K. Hartmann
S. Krasemann
A. Kurth
J. Prescott
Inoculation route-dependent Lassa virus dissemination and shedding dynamics in the natural reservoir – Mastomys natalensis
Emerging Microbes and Infections
Lassa virus
LASV
Mastomys natalensis
dissemination
shedding
natural reservoir
title Inoculation route-dependent Lassa virus dissemination and shedding dynamics in the natural reservoir – Mastomys natalensis
title_full Inoculation route-dependent Lassa virus dissemination and shedding dynamics in the natural reservoir – Mastomys natalensis
title_fullStr Inoculation route-dependent Lassa virus dissemination and shedding dynamics in the natural reservoir – Mastomys natalensis
title_full_unstemmed Inoculation route-dependent Lassa virus dissemination and shedding dynamics in the natural reservoir – Mastomys natalensis
title_short Inoculation route-dependent Lassa virus dissemination and shedding dynamics in the natural reservoir – Mastomys natalensis
title_sort inoculation route dependent lassa virus dissemination and shedding dynamics in the natural reservoir mastomys natalensis
topic Lassa virus
LASV
Mastomys natalensis
dissemination
shedding
natural reservoir
url https://www.tandfonline.com/doi/10.1080/22221751.2021.2008773
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