TIM-1 serves as a receptor for Ebola virus in vivo, enhancing viremia and pathogenesis.
Background T cell immunoglobulin mucin domain-1 (TIM-1) is a phosphatidylserine (PS) receptor, mediating filovirus entry into cells through interactions with PS on virions. TIM-1 expression has been implicated in Ebola virus (EBOV) pathogenesis; however, it remains unclear whether this is due to TIM...
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ftdoajarticles:oai:doaj.org/article:89c8289d298c42bc89c8d360269b55f1 2023-05-15T15:17:06+02:00 TIM-1 serves as a receptor for Ebola virus in vivo, enhancing viremia and pathogenesis. Bethany Brunton Kai Rogers Elisabeth K Phillips Rachel B Brouillette Ruayda Bouls Noah S Butler Wendy Maury 2019-06-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0006983 https://doaj.org/article/89c8289d298c42bc89c8d360269b55f1 EN eng Public Library of Science (PLoS) https://doi.org/10.1371/journal.pntd.0006983 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0006983 https://doaj.org/article/89c8289d298c42bc89c8d360269b55f1 PLoS Neglected Tropical Diseases, Vol 13, Iss 6, p e0006983 (2019) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2019 ftdoajarticles https://doi.org/10.1371/journal.pntd.0006983 2022-12-31T13:14:37Z Background T cell immunoglobulin mucin domain-1 (TIM-1) is a phosphatidylserine (PS) receptor, mediating filovirus entry into cells through interactions with PS on virions. TIM-1 expression has been implicated in Ebola virus (EBOV) pathogenesis; however, it remains unclear whether this is due to TIM-1 serving as a filovirus receptor in vivo or, as others have suggested, TIM-1 induces a cytokine storm elicited by T cell/virion interactions. Here, we use a BSL2 model virus that expresses EBOV glycoprotein to demonstrate the importance of TIM-1 as a virus receptor late during in vivo infection. Methodology/principal findings Infectious, GFP-expressing recombinant vesicular stomatitis virus encoding either full length EBOV glycoprotein (EBOV GP/rVSV) or mucin domain deleted EBOV glycoprotein (EBOV GPΔO/rVSV) was used to assess the role of TIM-1 during in vivo infection. GFP-expressing rVSV encoding its native glycoprotein G (G/rVSV) served as a control. TIM-1-sufficient or TIM-1-deficient BALB/c interferon α/β receptor-/- mice were challenged with these viruses. While G/rVSV caused profound morbidity and mortality in both mouse strains, TIM-1-deficient mice had significantly better survival than TIM-1-expressing mice following EBOV GP/rVSV or EBOV GPΔO/rVSV challenge. EBOV GP/rVSV or EBOV GPΔO/rVSV in spleen of infected animals was high and unaffected by expression of TIM-1. However, infectious virus in serum, liver, kidney and adrenal gland was reduced late in infection in the TIM-1-deficient mice, suggesting that virus entry via this receptor contributes to virus load. Consistent with higher virus loads, proinflammatory chemokines trended higher in organs from infected TIM-1-sufficient mice compared to the TIM-1-deficient mice, but proinflammatory cytokines were more modestly affected. To assess the role of T cells in EBOV GP/rVSV pathogenesis, T cells were depleted in TIM-1-sufficient and -deficient mice and the mice were challenged with virus. Depletion of T cells did not alter the pathogenic consequences of ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 13 6 e0006983 |
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Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
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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 Bethany Brunton Kai Rogers Elisabeth K Phillips Rachel B Brouillette Ruayda Bouls Noah S Butler Wendy Maury TIM-1 serves as a receptor for Ebola virus in vivo, enhancing viremia and pathogenesis. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Background T cell immunoglobulin mucin domain-1 (TIM-1) is a phosphatidylserine (PS) receptor, mediating filovirus entry into cells through interactions with PS on virions. TIM-1 expression has been implicated in Ebola virus (EBOV) pathogenesis; however, it remains unclear whether this is due to TIM-1 serving as a filovirus receptor in vivo or, as others have suggested, TIM-1 induces a cytokine storm elicited by T cell/virion interactions. Here, we use a BSL2 model virus that expresses EBOV glycoprotein to demonstrate the importance of TIM-1 as a virus receptor late during in vivo infection. Methodology/principal findings Infectious, GFP-expressing recombinant vesicular stomatitis virus encoding either full length EBOV glycoprotein (EBOV GP/rVSV) or mucin domain deleted EBOV glycoprotein (EBOV GPΔO/rVSV) was used to assess the role of TIM-1 during in vivo infection. GFP-expressing rVSV encoding its native glycoprotein G (G/rVSV) served as a control. TIM-1-sufficient or TIM-1-deficient BALB/c interferon α/β receptor-/- mice were challenged with these viruses. While G/rVSV caused profound morbidity and mortality in both mouse strains, TIM-1-deficient mice had significantly better survival than TIM-1-expressing mice following EBOV GP/rVSV or EBOV GPΔO/rVSV challenge. EBOV GP/rVSV or EBOV GPΔO/rVSV in spleen of infected animals was high and unaffected by expression of TIM-1. However, infectious virus in serum, liver, kidney and adrenal gland was reduced late in infection in the TIM-1-deficient mice, suggesting that virus entry via this receptor contributes to virus load. Consistent with higher virus loads, proinflammatory chemokines trended higher in organs from infected TIM-1-sufficient mice compared to the TIM-1-deficient mice, but proinflammatory cytokines were more modestly affected. To assess the role of T cells in EBOV GP/rVSV pathogenesis, T cells were depleted in TIM-1-sufficient and -deficient mice and the mice were challenged with virus. Depletion of T cells did not alter the pathogenic consequences of ... |
format |
Article in Journal/Newspaper |
author |
Bethany Brunton Kai Rogers Elisabeth K Phillips Rachel B Brouillette Ruayda Bouls Noah S Butler Wendy Maury |
author_facet |
Bethany Brunton Kai Rogers Elisabeth K Phillips Rachel B Brouillette Ruayda Bouls Noah S Butler Wendy Maury |
author_sort |
Bethany Brunton |
title |
TIM-1 serves as a receptor for Ebola virus in vivo, enhancing viremia and pathogenesis. |
title_short |
TIM-1 serves as a receptor for Ebola virus in vivo, enhancing viremia and pathogenesis. |
title_full |
TIM-1 serves as a receptor for Ebola virus in vivo, enhancing viremia and pathogenesis. |
title_fullStr |
TIM-1 serves as a receptor for Ebola virus in vivo, enhancing viremia and pathogenesis. |
title_full_unstemmed |
TIM-1 serves as a receptor for Ebola virus in vivo, enhancing viremia and pathogenesis. |
title_sort |
tim-1 serves as a receptor for ebola virus in vivo, enhancing viremia and pathogenesis. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2019 |
url |
https://doi.org/10.1371/journal.pntd.0006983 https://doaj.org/article/89c8289d298c42bc89c8d360269b55f1 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 13, Iss 6, p e0006983 (2019) |
op_relation |
https://doi.org/10.1371/journal.pntd.0006983 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0006983 https://doaj.org/article/89c8289d298c42bc89c8d360269b55f1 |
op_doi |
https://doi.org/10.1371/journal.pntd.0006983 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
13 |
container_issue |
6 |
container_start_page |
e0006983 |
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1766347372357484544 |