FAS-associated factor-1 positively regulates type I interferon response to RNA virus infection by targeting NLRX1

Jae Hoon Kim; Min Eun Park; Chamilani Nikapitiya; Tae Hwan Kim; Md Bashir Uddin; Hyun Cheol Lee; Eunhee Kim; Jin Yeul Ma; Jae U. Jung; Chul Joong Kim; Jong Soo Lee

doi:10.1371/journal.ppat.1006398

FAS-associated factor-1 positively regulates type I interferon response to RNA virus infection by targeting NLRX1

Jae Hoon Kim, Min Eun Park, Chamilani Nikapitiya, Tae Hwan Kim, Md Bashir Uddin, Hyun Cheol Lee, Eunhee Kim, Jin Yeul Ma, Jae U. Jung, Chul Joong Kim, Jong Soo Lee

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

Abstract

FAS-associated factor-1 (FAF1) is a component of the death-inducing signaling complex involved in Fas-mediated apoptosis. It regulates NF-κB activity, ubiquitination, and proteasomal degradation. Here, we found that FAF1 positively regulates the type I interferon pathway. FAF1^gt/gtmice, which deficient in FAF1, and FAF1 knockdown immune cells were highly susceptible to RNA virus infection and showed low levels of inflammatory cytokines and type I interferon (IFN) production. FAF1 was bound competitively to NLRX1 and positively regulated type I IFN signaling by interfering with the interaction between NLRX1 and MAVS, thereby freeing MAVS to bind RIG-I, which switched on the MAVS-RIG-I-mediated antiviral signaling cascade. These results highlight a critical role of FAF1 in antiviral responses against RNA virus infection.

Original language	English (US)
Article number	e1006398
Journal	PLoS pathogens
Volume	13
Issue number	5
DOIs	https://doi.org/10.1371/journal.ppat.1006398
State	Published - May 2017
Externally published	Yes

ASJC Scopus subject areas

Parasitology
Microbiology
Immunology
Molecular Biology
Genetics
Virology

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10.1371/journal.ppat.1006398

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title = "FAS-associated factor-1 positively regulates type I interferon response to RNA virus infection by targeting NLRX1",

abstract = "FAS-associated factor-1 (FAF1) is a component of the death-inducing signaling complex involved in Fas-mediated apoptosis. It regulates NF-κB activity, ubiquitination, and proteasomal degradation. Here, we found that FAF1 positively regulates the type I interferon pathway. FAF1gt/gtmice, which deficient in FAF1, and FAF1 knockdown immune cells were highly susceptible to RNA virus infection and showed low levels of inflammatory cytokines and type I interferon (IFN) production. FAF1 was bound competitively to NLRX1 and positively regulated type I IFN signaling by interfering with the interaction between NLRX1 and MAVS, thereby freeing MAVS to bind RIG-I, which switched on the MAVS-RIG-I-mediated antiviral signaling cascade. These results highlight a critical role of FAF1 in antiviral responses against RNA virus infection.",

author = "Kim, {Jae Hoon} and Park, {Min Eun} and Chamilani Nikapitiya and Kim, {Tae Hwan} and Uddin, {Md Bashir} and Lee, {Hyun Cheol} and Eunhee Kim and Ma, {Jin Yeul} and Jung, {Jae U.} and Kim, {Chul Joong} and Lee, {Jong Soo}",

note = "Publisher Copyright: {\textcopyright} 2017 Kim et al.",

year = "2017",

month = may,

doi = "10.1371/journal.ppat.1006398",

language = "English (US)",

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AU - Kim, Jae Hoon

AU - Park, Min Eun

AU - Nikapitiya, Chamilani

AU - Kim, Tae Hwan

AU - Uddin, Md Bashir

AU - Lee, Hyun Cheol

AU - Kim, Eunhee

AU - Ma, Jin Yeul

AU - Jung, Jae U.

AU - Kim, Chul Joong

AU - Lee, Jong Soo

PY - 2017/5

Y1 - 2017/5

N2 - FAS-associated factor-1 (FAF1) is a component of the death-inducing signaling complex involved in Fas-mediated apoptosis. It regulates NF-κB activity, ubiquitination, and proteasomal degradation. Here, we found that FAF1 positively regulates the type I interferon pathway. FAF1gt/gtmice, which deficient in FAF1, and FAF1 knockdown immune cells were highly susceptible to RNA virus infection and showed low levels of inflammatory cytokines and type I interferon (IFN) production. FAF1 was bound competitively to NLRX1 and positively regulated type I IFN signaling by interfering with the interaction between NLRX1 and MAVS, thereby freeing MAVS to bind RIG-I, which switched on the MAVS-RIG-I-mediated antiviral signaling cascade. These results highlight a critical role of FAF1 in antiviral responses against RNA virus infection.

AB - FAS-associated factor-1 (FAF1) is a component of the death-inducing signaling complex involved in Fas-mediated apoptosis. It regulates NF-κB activity, ubiquitination, and proteasomal degradation. Here, we found that FAF1 positively regulates the type I interferon pathway. FAF1gt/gtmice, which deficient in FAF1, and FAF1 knockdown immune cells were highly susceptible to RNA virus infection and showed low levels of inflammatory cytokines and type I interferon (IFN) production. FAF1 was bound competitively to NLRX1 and positively regulated type I IFN signaling by interfering with the interaction between NLRX1 and MAVS, thereby freeing MAVS to bind RIG-I, which switched on the MAVS-RIG-I-mediated antiviral signaling cascade. These results highlight a critical role of FAF1 in antiviral responses against RNA virus infection.

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FAS-associated factor-1 positively regulates type I interferon response to RNA virus infection by targeting NLRX1

Abstract

ASJC Scopus subject areas

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