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Long-term persistence of viral RNA and inflammation in the CNS of macaques exposed to aerosolized Venezuelan equine encephalitis virus

Venezuelan equine encephalitis virus (VEEV) is a positively-stranded RNA arbovirus of the genus Alphavirus that causes encephalitis in humans. Cynomolgus macaques are a relevant model of the human disease caused by VEEV and are useful in exploring pathogenic mechanisms and the host response to VEEV...

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Autores principales: Ma, Henry, Albe, Joseph R., Gilliland, Theron, McMillen, Cynthia M., Gardner, Christina L., Boyles, Devin A., Cottle, Emily L., Dunn, Matthew D., Lundy, Jeneveve D., Salama, Noah, O’Malley, Katherine J., Pandrea, Ivona, Teichert, Tobias, Barrick, Stacey, Klimstra, William B., Hartman, Amy L., Reed, Douglas S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9232170/
https://www.ncbi.nlm.nih.gov/pubmed/35696423
http://dx.doi.org/10.1371/journal.ppat.1009946
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author Ma, Henry
Albe, Joseph R.
Gilliland, Theron
McMillen, Cynthia M.
Gardner, Christina L.
Boyles, Devin A.
Cottle, Emily L.
Dunn, Matthew D.
Lundy, Jeneveve D.
Salama, Noah
O’Malley, Katherine J.
Pandrea, Ivona
Teichert, Tobias
Barrick, Stacey
Klimstra, William B.
Hartman, Amy L.
Reed, Douglas S.
author_facet Ma, Henry
Albe, Joseph R.
Gilliland, Theron
McMillen, Cynthia M.
Gardner, Christina L.
Boyles, Devin A.
Cottle, Emily L.
Dunn, Matthew D.
Lundy, Jeneveve D.
Salama, Noah
O’Malley, Katherine J.
Pandrea, Ivona
Teichert, Tobias
Barrick, Stacey
Klimstra, William B.
Hartman, Amy L.
Reed, Douglas S.
author_sort Ma, Henry
collection PubMed
description Venezuelan equine encephalitis virus (VEEV) is a positively-stranded RNA arbovirus of the genus Alphavirus that causes encephalitis in humans. Cynomolgus macaques are a relevant model of the human disease caused by VEEV and are useful in exploring pathogenic mechanisms and the host response to VEEV infection. Macaques were exposed to small-particle aerosols containing virus derived from an infectious clone of VEEV strain INH-9813, a subtype IC strain isolated from a human infection. VEEV-exposed macaques developed a biphasic fever after infection similar to that seen in humans. Maximum temperature deviation correlated with the inhaled dose, but fever duration did not. Neurological signs, suggestive of virus penetration into the central nervous system (CNS), were predominantly seen in the second febrile period. Electroencephalography data indicated a statistically significant decrease in all power bands and circadian index during the second febrile period that returned to normal after fever resolved. Intracranial pressure increased late in the second febrile period. On day 6 post-infection macaques had high levels of MCP-1 and IP-10 chemokines in the CNS, as well as a marked increase of T lymphocytes and activated microglia. More than four weeks after infection, VEEV genomic RNA was found in the brain, cerebrospinal fluid and cervical lymph nodes. Pro-inflammatory cytokines & chemokines, infiltrating leukocytes and pathological changes were seen in the CNS tissues of macaques euthanized at these times. These data are consistent with persistence of virus replication and/or genomic RNA and potentially, inflammatory sequelae in the central nervous system after resolution of acute VEEV disease.
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spelling pubmed-92321702022-06-25 Long-term persistence of viral RNA and inflammation in the CNS of macaques exposed to aerosolized Venezuelan equine encephalitis virus Ma, Henry Albe, Joseph R. Gilliland, Theron McMillen, Cynthia M. Gardner, Christina L. Boyles, Devin A. Cottle, Emily L. Dunn, Matthew D. Lundy, Jeneveve D. Salama, Noah O’Malley, Katherine J. Pandrea, Ivona Teichert, Tobias Barrick, Stacey Klimstra, William B. Hartman, Amy L. Reed, Douglas S. PLoS Pathog Research Article Venezuelan equine encephalitis virus (VEEV) is a positively-stranded RNA arbovirus of the genus Alphavirus that causes encephalitis in humans. Cynomolgus macaques are a relevant model of the human disease caused by VEEV and are useful in exploring pathogenic mechanisms and the host response to VEEV infection. Macaques were exposed to small-particle aerosols containing virus derived from an infectious clone of VEEV strain INH-9813, a subtype IC strain isolated from a human infection. VEEV-exposed macaques developed a biphasic fever after infection similar to that seen in humans. Maximum temperature deviation correlated with the inhaled dose, but fever duration did not. Neurological signs, suggestive of virus penetration into the central nervous system (CNS), were predominantly seen in the second febrile period. Electroencephalography data indicated a statistically significant decrease in all power bands and circadian index during the second febrile period that returned to normal after fever resolved. Intracranial pressure increased late in the second febrile period. On day 6 post-infection macaques had high levels of MCP-1 and IP-10 chemokines in the CNS, as well as a marked increase of T lymphocytes and activated microglia. More than four weeks after infection, VEEV genomic RNA was found in the brain, cerebrospinal fluid and cervical lymph nodes. Pro-inflammatory cytokines & chemokines, infiltrating leukocytes and pathological changes were seen in the CNS tissues of macaques euthanized at these times. These data are consistent with persistence of virus replication and/or genomic RNA and potentially, inflammatory sequelae in the central nervous system after resolution of acute VEEV disease. Public Library of Science 2022-06-13 /pmc/articles/PMC9232170/ /pubmed/35696423 http://dx.doi.org/10.1371/journal.ppat.1009946 Text en © 2022 Ma et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Ma, Henry
Albe, Joseph R.
Gilliland, Theron
McMillen, Cynthia M.
Gardner, Christina L.
Boyles, Devin A.
Cottle, Emily L.
Dunn, Matthew D.
Lundy, Jeneveve D.
Salama, Noah
O’Malley, Katherine J.
Pandrea, Ivona
Teichert, Tobias
Barrick, Stacey
Klimstra, William B.
Hartman, Amy L.
Reed, Douglas S.
Long-term persistence of viral RNA and inflammation in the CNS of macaques exposed to aerosolized Venezuelan equine encephalitis virus
title Long-term persistence of viral RNA and inflammation in the CNS of macaques exposed to aerosolized Venezuelan equine encephalitis virus
title_full Long-term persistence of viral RNA and inflammation in the CNS of macaques exposed to aerosolized Venezuelan equine encephalitis virus
title_fullStr Long-term persistence of viral RNA and inflammation in the CNS of macaques exposed to aerosolized Venezuelan equine encephalitis virus
title_full_unstemmed Long-term persistence of viral RNA and inflammation in the CNS of macaques exposed to aerosolized Venezuelan equine encephalitis virus
title_short Long-term persistence of viral RNA and inflammation in the CNS of macaques exposed to aerosolized Venezuelan equine encephalitis virus
title_sort long-term persistence of viral rna and inflammation in the cns of macaques exposed to aerosolized venezuelan equine encephalitis virus
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9232170/
https://www.ncbi.nlm.nih.gov/pubmed/35696423
http://dx.doi.org/10.1371/journal.ppat.1009946
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