scholarly journals CD40L protects against mouse hepatitis virus-induced neuroinflammatory demyelination

2021 ◽  
Vol 17 (12) ◽  
pp. e1010059
Author(s):  
Fareeha Saadi ◽  
Debanjana Chakravarty ◽  
Saurav Kumar ◽  
Mithila Kamble ◽  
Bhaskar Saha ◽  
...  
Keyword(s):  
Macrophage Activation ◽  
Axonal Degeneration ◽  
Hepatitis Virus ◽  
Mouse Hepatitis Virus ◽  
Protective Role ◽  
Axonal Loss ◽  
Pathogenic Role ◽  
Show Evidence ◽  
Novel Target

Neurotropic mouse hepatitis virus (MHV-A59/RSA59) infection in mice induces acute neuroinflammation due to direct neural cell dystrophy, which proceeds with demyelination with or without axonal loss, the pathological hallmarks of human neurological disease, Multiple sclerosis (MS). Recent studies in the RSA59-induced neuroinflammation model of MS showed a protective role of CNS-infiltrating CD4+ T cells compared to their pathogenic role in the autoimmune model. The current study further investigated the molecular nexus between CD4+T cell-expressed CD40Ligand and microglia/macrophage-expressed CD40 using CD40L-/- mice. Results demonstrate CD40L expression in the CNS is modulated upon RSA59 infection. We show evidence that CD40L-/- mice are more susceptible to RSA59 induced disease due to reduced microglia/macrophage activation and significantly dampened effector CD4+ T recruitment to the CNS on day 10 p.i. Additionally, CD40L-/- mice exhibited severe demyelination mediated by phagocytic microglia/macrophages, axonal loss, and persistent poliomyelitis during chronic infection, indicating CD40-CD40L as host-protective against RSA59-induced demyelination. This suggests a novel target in designing prophylaxis for virus-induced demyelination and axonal degeneration, in contrast to immunosuppression which holds only for autoimmune mechanisms of inflammatory demyelination.

The Role of B Cells in Mouse Hepatitis Virus Infection and Pathology

2001 ◽  
pp. 363-368 ◽  
Author(s):  
Amy E. Matthews ◽  
Susan R. Weiss ◽  
Ehud Lavi ◽  
Mark Shlomchik ◽  
Yvonne Paterson
Keyword(s):  
B Cells ◽  
Virus Infection ◽  
Hepatitis Virus ◽  
Mouse Hepatitis Virus ◽  
Hepatitis Virus Infection

scholarly journals MicroRNA-709 Mediates Acute Tubular Injury through Effects on Mitochondrial Function

2017 ◽  
Vol 29 (2) ◽  
pp. 449-461 ◽  
Author(s):  
Yan Guo ◽  
Jiajia Ni ◽  
Shuang Chen ◽  
Mi Bai ◽  
Jiajuan Lin ◽  
...  
Keyword(s):  
Mitochondrial Dysfunction ◽  
Mitochondrial Function ◽  
Cell Injury ◽  
Kidney Tissue ◽  
Kidney Injury ◽  
Tubular Injury ◽  
Pathogenic Role ◽  
Novel Target

Mitochondrial dysfunction has important roles in the pathogenesis of AKI, yet therapeutic approaches to improve mitochondrial function remain limited. In this study, we investigated the pathogenic role of microRNA-709 (miR-709) in mediating mitochondrial impairment and tubular cell death in AKI. In a cisplatin-induced AKI mouse model and in biopsy samples of human AKI kidney tissue, miR-709 was significantly upregulated in the proximal tubular cells (PTCs). The expression of miR-709 in the renal PTCs of patients with AKI correlated with the severity of kidney injury. In cultured mouse PTCs, overexpression of miR-709 markedly induced mitochondrial dysfunction and cell apoptosis, and inhibition of miR-709 ameliorated cisplatin-induced mitochondrial dysfunction and cell injury. Further analyses showed that mitochondrial transcriptional factor A (TFAM) is a target gene of miR-709, and genetic restoration of TFAM attenuated mitochondrial dysfunction and cell injury induced by cisplatin or miR-709 overexpression in vitro. Moreover, antagonizing miR-709 with an miR-709 antagomir dramatically attenuated cisplatin-induced kidney injury and mitochondrial dysfunction in mice. Collectively, our results suggest that miR-709 has an important role in mediating cisplatin-induced AKI via negative regulation of TFAM and subsequent mitochondrial dysfunction. These findings reveal a pathogenic role of miR-709 in acute tubular injury and suggest a novel target for the treatment of AKI.

scholarly journals The Role of IL-10 in Mouse Hepatitis Virus-Induced Demyelinating Encephalomyelitis

Virology ◽  
1998 ◽  
Vol 245 (2) ◽  
pp. 270-280 ◽  
Author(s):  
Mark T. Lin ◽  
David R. Hinton ◽  
Beatriz Parra ◽  
Stephen A. Stohlman ◽  
Roel C. van der Veen
Keyword(s):  
Hepatitis Virus ◽  
Mouse Hepatitis Virus
Sign in / Sign up

Export Citation Format

Share Document