Id |
Subject |
Object |
Predicate |
Lexical cue |
T1 |
0-150 |
Sentence |
denotes |
Toll-Like Receptor 3 Signaling via TRIF Contributes to a Protective Innate Immune Response to Severe Acute Respiratory Syndrome Coronavirus Infection. |
T2 |
151-162 |
Sentence |
denotes |
UNLABELLED: |
T3 |
163-328 |
Sentence |
denotes |
Toll-like receptors (TLRs) are sensors that recognize molecular patterns from viruses, bacteria, and fungi to initiate innate immune responses to invading pathogens. |
T4 |
329-623 |
Sentence |
denotes |
The emergence of highly pathogenic coronaviruses severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) is a concern for global public health, as there is a lack of efficacious vaccine platforms and antiviral therapeutic strategies. |
T5 |
624-820 |
Sentence |
denotes |
Previously, it was shown that MyD88, an adaptor protein necessary for signaling by multiple TLRs, is a required component of the innate immune response to mouse-adapted SARS-CoV infection in vivo. |
T6 |
821-1026 |
Sentence |
denotes |
Here, we demonstrate that TLR3(-/-), TLR4(-/-), and TRAM(-/-) mice are more susceptible to SARS-CoV than wild-type mice but experience only transient weight loss with no mortality in response to infection. |
T7 |
1027-1246 |
Sentence |
denotes |
In contrast, mice deficient in the TLR3/TLR4 adaptor TRIF are highly susceptible to SARS-CoV infection, showing increased weight loss, mortality, reduced lung function, increased lung pathology, and higher viral titers. |
T8 |
1247-1558 |
Sentence |
denotes |
Distinct alterations in inflammation were present in TRIF(-/-) mice infected with SARS-CoV, including excess infiltration of neutrophils and inflammatory cell types that correlate with increased pathology of other known causes of acute respiratory distress syndrome (ARDS), including influenza virus infections. |
T9 |
1559-1832 |
Sentence |
denotes |
Aberrant proinflammatory cytokine, chemokine, and interferon-stimulated gene (ISG) signaling programs were also noted following infection of TRIF(-/-) mice that were similar to those seen in human patients with poor disease outcome following SARS-CoV or MERS-CoV infection. |
T10 |
1833-2001 |
Sentence |
denotes |
These findings highlight the importance of TLR adaptor signaling in generating a balanced protective innate immune response to highly pathogenic coronavirus infections. |
T11 |
2002-2013 |
Sentence |
denotes |
IMPORTANCE: |
T12 |
2014-2256 |
Sentence |
denotes |
Toll-like receptors are a family of sensor proteins that enable the immune system to differentiate between "self" and "non-self." Agonists and antagonists of TLRs have been proposed to have utility as vaccine adjuvants or antiviral compounds. |
T13 |
2257-2506 |
Sentence |
denotes |
In the last 15 years, the emergence of highly pathogenic coronaviruses SARS-CoV and MERS-CoV has caused significant disease accompanied by high mortality rates in human populations, but no approved therapeutic treatments or vaccines currently exist. |
T14 |
2507-2623 |
Sentence |
denotes |
Here, we demonstrate that TLR signaling through the TRIF adaptor protein protects mice from lethal SARS-CoV disease. |
T15 |
2624-2948 |
Sentence |
denotes |
Our findings indicate that a balanced immune response operating through both TRIF-driven and MyD88-driven pathways likely provides the most effective host cell intrinsic antiviral defense responses to severe SARS-CoV disease, while removal of either branch of TLR signaling causes lethal SARS-CoV disease in our mouse model. |
T16 |
2949-3082 |
Sentence |
denotes |
These data should inform the design and use of TLR agonists and antagonists in coronavirus-specific vaccine and antiviral strategies. |
T1 |
0-150 |
Sentence |
denotes |
Toll-Like Receptor 3 Signaling via TRIF Contributes to a Protective Innate Immune Response to Severe Acute Respiratory Syndrome Coronavirus Infection. |
T2 |
151-162 |
Sentence |
denotes |
UNLABELLED: |
T3 |
163-328 |
Sentence |
denotes |
Toll-like receptors (TLRs) are sensors that recognize molecular patterns from viruses, bacteria, and fungi to initiate innate immune responses to invading pathogens. |
T4 |
329-623 |
Sentence |
denotes |
The emergence of highly pathogenic coronaviruses severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) is a concern for global public health, as there is a lack of efficacious vaccine platforms and antiviral therapeutic strategies. |
T5 |
624-820 |
Sentence |
denotes |
Previously, it was shown that MyD88, an adaptor protein necessary for signaling by multiple TLRs, is a required component of the innate immune response to mouse-adapted SARS-CoV infection in vivo. |
T6 |
821-1026 |
Sentence |
denotes |
Here, we demonstrate that TLR3(-/-), TLR4(-/-), and TRAM(-/-) mice are more susceptible to SARS-CoV than wild-type mice but experience only transient weight loss with no mortality in response to infection. |
T7 |
1027-1246 |
Sentence |
denotes |
In contrast, mice deficient in the TLR3/TLR4 adaptor TRIF are highly susceptible to SARS-CoV infection, showing increased weight loss, mortality, reduced lung function, increased lung pathology, and higher viral titers. |
T8 |
1247-1558 |
Sentence |
denotes |
Distinct alterations in inflammation were present in TRIF(-/-) mice infected with SARS-CoV, including excess infiltration of neutrophils and inflammatory cell types that correlate with increased pathology of other known causes of acute respiratory distress syndrome (ARDS), including influenza virus infections. |
T9 |
1559-1832 |
Sentence |
denotes |
Aberrant proinflammatory cytokine, chemokine, and interferon-stimulated gene (ISG) signaling programs were also noted following infection of TRIF(-/-) mice that were similar to those seen in human patients with poor disease outcome following SARS-CoV or MERS-CoV infection. |
T10 |
1833-2001 |
Sentence |
denotes |
These findings highlight the importance of TLR adaptor signaling in generating a balanced protective innate immune response to highly pathogenic coronavirus infections. |
T11 |
2002-2013 |
Sentence |
denotes |
IMPORTANCE: |
T12 |
2014-2256 |
Sentence |
denotes |
Toll-like receptors are a family of sensor proteins that enable the immune system to differentiate between "self" and "non-self." Agonists and antagonists of TLRs have been proposed to have utility as vaccine adjuvants or antiviral compounds. |
T13 |
2257-2506 |
Sentence |
denotes |
In the last 15 years, the emergence of highly pathogenic coronaviruses SARS-CoV and MERS-CoV has caused significant disease accompanied by high mortality rates in human populations, but no approved therapeutic treatments or vaccines currently exist. |
T14 |
2507-2623 |
Sentence |
denotes |
Here, we demonstrate that TLR signaling through the TRIF adaptor protein protects mice from lethal SARS-CoV disease. |
T15 |
2624-2948 |
Sentence |
denotes |
Our findings indicate that a balanced immune response operating through both TRIF-driven and MyD88-driven pathways likely provides the most effective host cell intrinsic antiviral defense responses to severe SARS-CoV disease, while removal of either branch of TLR signaling causes lethal SARS-CoV disease in our mouse model. |
T16 |
2949-3082 |
Sentence |
denotes |
These data should inform the design and use of TLR agonists and antagonists in coronavirus-specific vaccine and antiviral strategies. |