Multiple immune factors are involved in controlling acute and chronic chikungunya virus infection.
The recent epidemic of the arthritogenic alphavirus, chikungunya virus (CHIKV) has prompted a quest to understand the correlates of protection against virus and disease in order to inform development of new interventions. Herein we highlight the propensity of CHIKV infections to persist long term, b...
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ftdoajarticles:oai:doaj.org/article:0aeed3112e6b4633b8b52c3cc6e95cd9 2023-05-15T15:13:35+02:00 Multiple immune factors are involved in controlling acute and chronic chikungunya virus infection. Yee Suan Poo Penny A Rudd Joy Gardner Jane A C Wilson Thibaut Larcher Marie-Anne Colle Thuy T Le Helder I Nakaya David Warrilow Richard Allcock Helle Bielefeldt-Ohmann Wayne A Schroder Alexander A Khromykh José A Lopez Andreas Suhrbier 2014-12-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0003354 https://doaj.org/article/0aeed3112e6b4633b8b52c3cc6e95cd9 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC4256279?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0003354 https://doaj.org/article/0aeed3112e6b4633b8b52c3cc6e95cd9 PLoS Neglected Tropical Diseases, Vol 8, Iss 12, p e3354 (2014) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2014 ftdoajarticles https://doi.org/10.1371/journal.pntd.0003354 2022-12-31T05:10:52Z The recent epidemic of the arthritogenic alphavirus, chikungunya virus (CHIKV) has prompted a quest to understand the correlates of protection against virus and disease in order to inform development of new interventions. Herein we highlight the propensity of CHIKV infections to persist long term, both as persistent, steady-state, viraemias in multiple B cell deficient mouse strains, and as persistent RNA (including negative-strand RNA) in wild-type mice. The knockout mouse studies provided evidence for a role for T cells (but not NK cells) in viraemia suppression, and confirmed the role of T cells in arthritis promotion, with vaccine-induced T cells also shown to be arthritogenic in the absence of antibody responses. However, MHC class II-restricted T cells were not required for production of anti-viral IgG2c responses post CHIKV infection. The anti-viral cytokines, TNF and IFNγ, were persistently elevated in persistently infected B and T cell deficient mice, with adoptive transfer of anti-CHIKV antibodies unable to clear permanently the viraemia from these, or B cell deficient, mice. The NOD background increased viraemia and promoted arthritis, with B, T and NK deficient NOD mice showing high-levels of persistent viraemia and ultimately succumbing to encephalitic disease. In wild-type mice persistent CHIKV RNA and negative strand RNA (detected for up to 100 days post infection) was associated with persistence of cellular infiltrates, CHIKV antigen and stimulation of IFNα/β and T cell responses. These studies highlight that, secondary to antibodies, several factors are involved in virus control, and suggest that chronic arthritic disease is a consequence of persistent, replicating and transcriptionally active CHIKV RNA. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLoS Neglected Tropical Diseases 8 12 e3354 |
institution |
Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Yee Suan Poo Penny A Rudd Joy Gardner Jane A C Wilson Thibaut Larcher Marie-Anne Colle Thuy T Le Helder I Nakaya David Warrilow Richard Allcock Helle Bielefeldt-Ohmann Wayne A Schroder Alexander A Khromykh José A Lopez Andreas Suhrbier Multiple immune factors are involved in controlling acute and chronic chikungunya virus infection. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
The recent epidemic of the arthritogenic alphavirus, chikungunya virus (CHIKV) has prompted a quest to understand the correlates of protection against virus and disease in order to inform development of new interventions. Herein we highlight the propensity of CHIKV infections to persist long term, both as persistent, steady-state, viraemias in multiple B cell deficient mouse strains, and as persistent RNA (including negative-strand RNA) in wild-type mice. The knockout mouse studies provided evidence for a role for T cells (but not NK cells) in viraemia suppression, and confirmed the role of T cells in arthritis promotion, with vaccine-induced T cells also shown to be arthritogenic in the absence of antibody responses. However, MHC class II-restricted T cells were not required for production of anti-viral IgG2c responses post CHIKV infection. The anti-viral cytokines, TNF and IFNγ, were persistently elevated in persistently infected B and T cell deficient mice, with adoptive transfer of anti-CHIKV antibodies unable to clear permanently the viraemia from these, or B cell deficient, mice. The NOD background increased viraemia and promoted arthritis, with B, T and NK deficient NOD mice showing high-levels of persistent viraemia and ultimately succumbing to encephalitic disease. In wild-type mice persistent CHIKV RNA and negative strand RNA (detected for up to 100 days post infection) was associated with persistence of cellular infiltrates, CHIKV antigen and stimulation of IFNα/β and T cell responses. These studies highlight that, secondary to antibodies, several factors are involved in virus control, and suggest that chronic arthritic disease is a consequence of persistent, replicating and transcriptionally active CHIKV RNA. |
format |
Article in Journal/Newspaper |
author |
Yee Suan Poo Penny A Rudd Joy Gardner Jane A C Wilson Thibaut Larcher Marie-Anne Colle Thuy T Le Helder I Nakaya David Warrilow Richard Allcock Helle Bielefeldt-Ohmann Wayne A Schroder Alexander A Khromykh José A Lopez Andreas Suhrbier |
author_facet |
Yee Suan Poo Penny A Rudd Joy Gardner Jane A C Wilson Thibaut Larcher Marie-Anne Colle Thuy T Le Helder I Nakaya David Warrilow Richard Allcock Helle Bielefeldt-Ohmann Wayne A Schroder Alexander A Khromykh José A Lopez Andreas Suhrbier |
author_sort |
Yee Suan Poo |
title |
Multiple immune factors are involved in controlling acute and chronic chikungunya virus infection. |
title_short |
Multiple immune factors are involved in controlling acute and chronic chikungunya virus infection. |
title_full |
Multiple immune factors are involved in controlling acute and chronic chikungunya virus infection. |
title_fullStr |
Multiple immune factors are involved in controlling acute and chronic chikungunya virus infection. |
title_full_unstemmed |
Multiple immune factors are involved in controlling acute and chronic chikungunya virus infection. |
title_sort |
multiple immune factors are involved in controlling acute and chronic chikungunya virus infection. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2014 |
url |
https://doi.org/10.1371/journal.pntd.0003354 https://doaj.org/article/0aeed3112e6b4633b8b52c3cc6e95cd9 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 8, Iss 12, p e3354 (2014) |
op_relation |
http://europepmc.org/articles/PMC4256279?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0003354 https://doaj.org/article/0aeed3112e6b4633b8b52c3cc6e95cd9 |
op_doi |
https://doi.org/10.1371/journal.pntd.0003354 |
container_title |
PLoS Neglected Tropical Diseases |
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8 |
container_issue |
12 |
container_start_page |
e3354 |
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