2. Academic Validation
  3. Viral proteases activate the CARD8 inflammasome in the human cardiovascular system

Viral proteases activate the CARD8 inflammasome in the human cardiovascular system

  • J Exp Med. 2022 Oct 3;219(10):e20212117. doi: 10.1084/jem.20212117.
Rhea Nadkarni  # 1,  Wern Cui Chu  # 1,  Cheryl Q E Lee  # 1,  Yasir Mohamud 2,  Lynn Yap 1,  Gee Ann Toh 3,  Sheryl Beh 1,  Radiance Lim 1,  Yiyun Michelle Fan 2,  Yizhuo Lyanne Zhang 2,  Kim Robinson 4,  Karl Tryggvason 1,  Honglin Luo 2,  Franklin Zhong 3 4,  Lena Ho  # 1 5
Affiliations

Affiliations

  • 1 Duke-NUS Medical School, Program in Cardiovascular and Metabolic Disorders, Singapore, Singapore.
  • 2 Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.
  • 3 Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, Singapore, Singapore.
  • 4 Skin Research Institute of Singapore, A*STAR, Singapore, Singapore.
  • 5 Institute of Molecular and Cell Biology, A*STAR, Singapore, Singapore.
  • # Contributed equally.
PMID: 36129453 DOI: 10.1084/jem.20212117
Abstract

Nucleotide-binding oligomerization domain (NBD), leucine-rich repeat (LRR) containing protein family (NLRs) are intracellular Pattern Recognition Receptors that mediate innate immunity against infections. The endothelium is the first line of defense against blood-borne pathogens, but it is unclear which NLRs control endothelial cell (EC) intrinsic immunity. Here, we demonstrate that human ECs simultaneously activate NLRP1 and CARD8 inflammasomes in response to DPP8/9 inhibitor Val-boro-Pro (VbP). Enterovirus Coxsackie virus B3 (CVB3)-the most common cause of viral myocarditis-predominantly activates CARD8 in ECs in a manner that requires viral 2A and 3C Protease cleavage at CARD8 p.G38 and Proteasome function. Genetic deletion of CARD8 in ECs and human embryonic stem cell-derived cardiomyocytes (HCMs) attenuates CVB3-induced Pyroptosis, inflammation, and viral propagation. Furthermore, using a stratified endothelial-cardiomyocyte co-culture system, we demonstrate that deleting CARD8 in ECs reduces CVB3 Infection of the underlying cardiomyocytes. Our study uncovers the unique role of CARD8 inflammasome in endothelium-intrinsic anti-viral immunity.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z