Distinct Roles of Type I and Type III Interferons during a Native Murine β Coronavirus Lung Infection

Lokesh Sharma; Xiaohua Peng; Hua Qing; Brandon K. Hilliard; Jooyoung Kim; Anush Swaminathan; Justin Tian; Kavita Israni-Winger; Cuiling Zhang; Victoria Habet; Lin Wang; Gayatri Gupta; Xuefei Tian; Yina Ma; Hyeon Jun Shin; Sang Hun Kim; Min Jong Kang; Shuta Ishibe; Lawrence H. Young; Sergei Kotenko; Susan Compton; Craig B. Wilen; Andrew Wang; Charles S. Dela Cruz

doi:https://doi.org/10.1128/JVI.01241-21

Distinct Roles of Type I and Type III Interferons during a Native Murine β Coronavirus Lung Infection

Lokesh Sharma, Xiaohua Peng, Hua Qing, Brandon K. Hilliard, Jooyoung Kim, Anush Swaminathan, Justin Tian, Kavita Israni-Winger, Cuiling Zhang, Victoria Habet, Lin Wang, Gayatri Gupta, Xuefei Tian, Yina Ma, Hyeon Jun Shin, Sang Hun Kim, Min Jong Kang, Shuta Ishibe, Lawrence H. Young, Sergei KotenkoSusan Compton, Craig B. Wilen, Andrew Wang, Charles S. Dela Cruz

Research output: Contribution to journal › Article › peer-review

Abstract

Coronaviruses are a major health care threat to humankind. Currently, the host factors that contribute to limit disease severity in healthy young patients are not well defined. Interferons are key antiviral molecules, especially type I and type III interferons. The role of these interferons during coronavirus disease is a subject of debate. Here, using mice that are deficient in type I (IFNAR12/2), type III (IFNLR12/2), or both (IFNAR1/LR12/2) interferon signaling pathways and murine-adapted coronavirus (MHV-A59) administered through the intranasal route, we define the role of interferons in coronavirus infection. We show that type I interferons play a major role in host survival in this model, while a minimal role of type III interferons was manifested only in the absence of type I interferons or during a lethal dose of coronavirus. IFNAR12/2 and IFNAR1/LR12/2 mice had an uncontrolled viral burden in the airways and lung and increased viral dissemination to other organs. The absence of only type III interferon signaling had no measurable difference in the viral load. The increased viral load in IFNAR12/2 and IFNAR1/LR12/2 mice was associated with increased tissue injury, especially evident in the lung and liver. Type I but not type III interferon treatment was able to promote survival if treated during early disease. Further, we show that type I interferon signaling in macrophages contributes to the beneficial effects during coronavirus infection in mice.

Original language	American English
Article number	e01241-21
Journal	Journal of virology
Volume	96
Issue number	2
DOIs	https://doi.org/10.1128/JVI.01241-21
State	Published - Jan 2022
Externally published	Yes

ASJC Scopus subject areas

Microbiology
Immunology
Insect Science
Virology

Keywords

Antiviral agents
Coronavirus
Lung defense
Type I interferons
Type III interferons

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https://doi.org/10.1128/JVI.01241-21

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Sharma, L., Peng, X., Qing, H., Hilliard, B. K., Kim, J., Swaminathan, A., Tian, J., Israni-Winger, K., Zhang, C., Habet, V., Wang, L., Gupta, G., Tian, X., Ma, Y., Shin, H. J., Kim, S. H., Kang, M. J., Ishibe, S., Young, L. H., ... Dela Cruz, C. S. (2022). Distinct Roles of Type I and Type III Interferons during a Native Murine β Coronavirus Lung Infection. Journal of virology, 96(2), [e01241-21]. https://doi.org/10.1128/JVI.01241-21

@article{9e7b505e5a87408397a6719256a178ad,

title = "Distinct Roles of Type I and Type III Interferons during a Native Murine β Coronavirus Lung Infection",

abstract = "Coronaviruses are a major health care threat to humankind. Currently, the host factors that contribute to limit disease severity in healthy young patients are not well defined. Interferons are key antiviral molecules, especially type I and type III interferons. The role of these interferons during coronavirus disease is a subject of debate. Here, using mice that are deficient in type I (IFNAR12/2), type III (IFNLR12/2), or both (IFNAR1/LR12/2) interferon signaling pathways and murine-adapted coronavirus (MHV-A59) administered through the intranasal route, we define the role of interferons in coronavirus infection. We show that type I interferons play a major role in host survival in this model, while a minimal role of type III interferons was manifested only in the absence of type I interferons or during a lethal dose of coronavirus. IFNAR12/2 and IFNAR1/LR12/2 mice had an uncontrolled viral burden in the airways and lung and increased viral dissemination to other organs. The absence of only type III interferon signaling had no measurable difference in the viral load. The increased viral load in IFNAR12/2 and IFNAR1/LR12/2 mice was associated with increased tissue injury, especially evident in the lung and liver. Type I but not type III interferon treatment was able to promote survival if treated during early disease. Further, we show that type I interferon signaling in macrophages contributes to the beneficial effects during coronavirus infection in mice.",

keywords = "Antiviral agents, Coronavirus, Lung defense, Type I interferons, Type III interferons",

author = "Lokesh Sharma and Xiaohua Peng and Hua Qing and Hilliard, {Brandon K.} and Jooyoung Kim and Anush Swaminathan and Justin Tian and Kavita Israni-Winger and Cuiling Zhang and Victoria Habet and Lin Wang and Gayatri Gupta and Xuefei Tian and Yina Ma and Shin, {Hyeon Jun} and Kim, {Sang Hun} and Kang, {Min Jong} and Shuta Ishibe and Young, {Lawrence H.} and Sergei Kotenko and Susan Compton and Wilen, {Craig B.} and Andrew Wang and {Dela Cruz}, {Charles S.}",

note = "Funding Information: Lokesh Sharma is supported by a Parker B. Francis Foundation award and a Catalyst Award from the American Lung Association. Andrew Wang is supported in part by NIH grant 1K08AI128745 and by generous gifts from the Pew Charitable Trusts, Knights of Columbus, G. Harold and Leila Y. Mathers Charitable Foundation, and the Ludwig Family Foundation. Charles Dela Cruz is supported by NIH grant HL126094, VA BX004661, Department of Defense. We have no competing interests. Publisher Copyright: Copyright {\textcopyright} 2022 American Society for Microbiology. All Rights Reserved.",

year = "2022",

month = jan,

doi = "https://doi.org/10.1128/JVI.01241-21",

language = "American English",

volume = "96",

journal = "Journal of virology",

issn = "0022-538X",

publisher = "American Society for Microbiology",

number = "2",

}

Sharma, L, Peng, X, Qing, H, Hilliard, BK, Kim, J, Swaminathan, A, Tian, J, Israni-Winger, K, Zhang, C, Habet, V, Wang, L, Gupta, G, Tian, X, Ma, Y, Shin, HJ, Kim, SH, Kang, MJ, Ishibe, S, Young, LH, Kotenko, S, Compton, S, Wilen, CB, Wang, A & Dela Cruz, CS 2022, 'Distinct Roles of Type I and Type III Interferons during a Native Murine β Coronavirus Lung Infection', Journal of virology, vol. 96, no. 2, e01241-21. https://doi.org/10.1128/JVI.01241-21

TY - JOUR

T1 - Distinct Roles of Type I and Type III Interferons during a Native Murine β Coronavirus Lung Infection

AU - Sharma, Lokesh

AU - Peng, Xiaohua

AU - Qing, Hua

AU - Hilliard, Brandon K.

AU - Kim, Jooyoung

AU - Swaminathan, Anush

AU - Tian, Justin

AU - Israni-Winger, Kavita

AU - Zhang, Cuiling

AU - Habet, Victoria

AU - Wang, Lin

AU - Gupta, Gayatri

AU - Tian, Xuefei

AU - Ma, Yina

AU - Shin, Hyeon Jun

AU - Kim, Sang Hun

AU - Kang, Min Jong

AU - Ishibe, Shuta

AU - Young, Lawrence H.

AU - Kotenko, Sergei

AU - Compton, Susan

AU - Wilen, Craig B.

AU - Wang, Andrew

AU - Dela Cruz, Charles S.

N1 - Funding Information: Lokesh Sharma is supported by a Parker B. Francis Foundation award and a Catalyst Award from the American Lung Association. Andrew Wang is supported in part by NIH grant 1K08AI128745 and by generous gifts from the Pew Charitable Trusts, Knights of Columbus, G. Harold and Leila Y. Mathers Charitable Foundation, and the Ludwig Family Foundation. Charles Dela Cruz is supported by NIH grant HL126094, VA BX004661, Department of Defense. We have no competing interests. Publisher Copyright: Copyright © 2022 American Society for Microbiology. All Rights Reserved.

PY - 2022/1

Y1 - 2022/1

N2 - Coronaviruses are a major health care threat to humankind. Currently, the host factors that contribute to limit disease severity in healthy young patients are not well defined. Interferons are key antiviral molecules, especially type I and type III interferons. The role of these interferons during coronavirus disease is a subject of debate. Here, using mice that are deficient in type I (IFNAR12/2), type III (IFNLR12/2), or both (IFNAR1/LR12/2) interferon signaling pathways and murine-adapted coronavirus (MHV-A59) administered through the intranasal route, we define the role of interferons in coronavirus infection. We show that type I interferons play a major role in host survival in this model, while a minimal role of type III interferons was manifested only in the absence of type I interferons or during a lethal dose of coronavirus. IFNAR12/2 and IFNAR1/LR12/2 mice had an uncontrolled viral burden in the airways and lung and increased viral dissemination to other organs. The absence of only type III interferon signaling had no measurable difference in the viral load. The increased viral load in IFNAR12/2 and IFNAR1/LR12/2 mice was associated with increased tissue injury, especially evident in the lung and liver. Type I but not type III interferon treatment was able to promote survival if treated during early disease. Further, we show that type I interferon signaling in macrophages contributes to the beneficial effects during coronavirus infection in mice.

AB - Coronaviruses are a major health care threat to humankind. Currently, the host factors that contribute to limit disease severity in healthy young patients are not well defined. Interferons are key antiviral molecules, especially type I and type III interferons. The role of these interferons during coronavirus disease is a subject of debate. Here, using mice that are deficient in type I (IFNAR12/2), type III (IFNLR12/2), or both (IFNAR1/LR12/2) interferon signaling pathways and murine-adapted coronavirus (MHV-A59) administered through the intranasal route, we define the role of interferons in coronavirus infection. We show that type I interferons play a major role in host survival in this model, while a minimal role of type III interferons was manifested only in the absence of type I interferons or during a lethal dose of coronavirus. IFNAR12/2 and IFNAR1/LR12/2 mice had an uncontrolled viral burden in the airways and lung and increased viral dissemination to other organs. The absence of only type III interferon signaling had no measurable difference in the viral load. The increased viral load in IFNAR12/2 and IFNAR1/LR12/2 mice was associated with increased tissue injury, especially evident in the lung and liver. Type I but not type III interferon treatment was able to promote survival if treated during early disease. Further, we show that type I interferon signaling in macrophages contributes to the beneficial effects during coronavirus infection in mice.

KW - Antiviral agents

KW - Coronavirus

KW - Lung defense

KW - Type I interferons

KW - Type III interferons

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UR - http://www.scopus.com/inward/citedby.url?scp=85123858767&partnerID=8YFLogxK

U2 - https://doi.org/10.1128/JVI.01241-21

DO - https://doi.org/10.1128/JVI.01241-21

M3 - Article

C2 - 34705554

SN - 0022-538X

VL - 96

JO - Journal of virology

JF - Journal of virology

IS - 2

M1 - e01241-21

ER -

Distinct Roles of Type I and Type III Interferons during a Native Murine β Coronavirus Lung Infection

Abstract

ASJC Scopus subject areas

Keywords

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