Case Report: Fulminant Myocarditis Successfully Treated With Extracorporeal Membrane Oxygenation in Ikeda Strain Orientia tsutsugamushi Infection

Park, Hyejin; Lim, Yoongho; Kim, Min Chul; Kim, Seong Eun; Jeong, In-Seok; Choi, Yoo Duk; Kim, Dong-Min

doi:10.3389/fcvm.2021.795249

Cited by 5 publications

(2 citation statements)

References 18 publications

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“…41 Ikeda, isolated from a patient in Japan, causes severe disease in humans and is fatal in laboratory mice. [42][43][44][45][46][47] It is the only microbe known to modulate MHC I cellular levels by targeting NLRC5, although the mechanism is uncharacterized.…”

Section: Introductionmentioning

confidence: 99%

Orientia tsutsugamushiAnk5 directs ubiquitination and proteasomal degradation of NLRC5 to inhibit major histocompatibility complex class I expression

Adcox,

Hunt,

Rodino

et al. 2023

Preprint

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How intracellular bacteria subvert the major histocompatibility complex (MHC) class I pathway is poorly understood. Here, we show that the obligate intracellular bacteriumOrientia tsutsugamushiuses its effector protein, Ank5, to orchestrate proteasomal degradation of the MHC class I gene transactivator, NLRC5. Ank5 uses a tyrosine in its fourth ankyrin repeat to bind the NLRC5 N-terminus while its F-box directs host SCF complex ubiquitination of K1194 in the leucine-rich repeat region that dictates NLRC5 susceptibility toOrientia- and Ank5-mediated degradation. The ability ofO. tsutsugamushistrains to degrade NLRC5 correlates withank5genomic carriage. Ectopically expressed Ank5 that can bind but not degrade NLRC5 protects the transactivator duringOrientiainfection. Thus, Ank5 is an immunoevasin that uses its bipartite architecture to rid host cells of NLRC5 and MHC class I molecules. This study offers insight into how intracellular pathogens can impair MHC class I expression to benefit their survival.

show abstract

Section: Introductionmentioning

confidence: 99%

Orientia tsutsugamushiAnk5 directs ubiquitination and proteasomal degradation of NLRC5 to inhibit major histocompatibility complex class I expression

Adcox,

Hunt,

Rodino

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…42 Ikeda, isolated from a patient in Japan, causes severe disease in humans and is fatal in laboratory mice. [43][44][45][46][47][48] It is the only microbe known to modulate MHC I cellular levels by targeting NLRC5, although the mechanism is uncharacterized.…”

Section: Introductionmentioning

confidence: 99%

Orientia tsutsugamushi Ank5 directs ubiquitination and proteasomal degradation of NLRC5 to inhibit major histocompatibility complex class I expression

Carlyon,

Adcox,

Hunt

et al. 2023

Preprint

View full text Add to dashboard Cite

How intracellular bacteria subvert the major histocompatibility complex (MHC) class I pathway is poorly understood. Here, we show that the obligate intracellular bacterium Orientia tsutsugamushi uses its effector protein, Ank5, to orchestrate proteasomal degradation of the MHC class I gene transactivator, NLRC5. Ank5 uses a tyrosine in its fourth ankyrin repeat to bind the NLRC5 N-terminus while its F-box directs host SCF complex ubiquitination of K1194 in the leucine-rich repeat region that dictates NLRC5 susceptibility to Orientia- and Ank5-mediated degradation. The ability of O. tsutsugamushi strains to degrade NLRC5 correlates with ank5 genomic carriage. Ectopically expressed Ank5 that can bind but not degrade NLRC5 protects the transactivator during Orientia infection. Thus, Ank5 is an immunoevasin that uses its bipartite architecture to rid host cells of NLRC5 and MHC class I molecules. This study offers insight into how intracellular pathogens can impair MHC class I expression to benefit their survival.

show abstract

Orientia tsutsugamushi Ank5 promotes NLRC5 cytoplasmic retention and degradation to inhibit MHC class I expression

Adcox,

Hunt,

Allen

et al. 2024

Nat Commun

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How intracellular bacteria subvert the major histocompatibility complex (MHC) class I pathway is poorly understood. Here, we show that the obligate intracellular bacterium Orientia tsutsugamushi uses its effector protein, Ank5, to inhibit nuclear translocation of the MHC class I gene transactivator, NLRC5, and orchestrate its proteasomal degradation. Ank5 uses a tyrosine in its fourth ankyrin repeat to bind the NLRC5 N-terminus while its F-box directs host SCF complex ubiquitination of NLRC5 in the leucine-rich repeat region that dictates susceptibility to Orientia - and Ank5-mediated degradation. The ability of O. tsutsugamushi strains to degrade NLRC5 correlates with ank5 genomic carriage. Ectopically expressed Ank5 that can bind but not degrade NLRC5 protects the transactivator during Orientia infection. Thus, Ank5 is an immunoevasin that uses its bipartite architecture to rid host cells of NLRC5 and reduce surface MHC class I molecules. This study offers insight into how intracellular pathogens can impair MHC class I expression.

show abstract

Case Report: Fulminant Myocarditis Successfully Treated With Extracorporeal Membrane Oxygenation in Ikeda Strain Orientia tsutsugamushi Infection

Cited by 5 publications

References 18 publications

Orientia tsutsugamushiAnk5 directs ubiquitination and proteasomal degradation of NLRC5 to inhibit major histocompatibility complex class I expression

Orientia tsutsugamushiAnk5 directs ubiquitination and proteasomal degradation of NLRC5 to inhibit major histocompatibility complex class I expression

Orientia tsutsugamushi Ank5 directs ubiquitination and proteasomal degradation of NLRC5 to inhibit major histocompatibility complex class I expression

Orientia tsutsugamushi Ank5 promotes NLRC5 cytoplasmic retention and degradation to inhibit MHC class I expression

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