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Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Viruses 2020 ; 12 (4): ä Nephropedia Template TP
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Interferon-lambda Attenuates Rabies Virus Infection by Inducing Interferon-Stimulated Genes and Alleviating Neurological Inflammation #MMPMID32268591
Li Y; Zhao L; Luo Z; Zhang Y; Lv L; Zhao J; Sui B; Huang F; Cui M; Fu ZF; Zhou M
Viruses 2020[Apr]; 12 (4): ä PMID32268591show ga
Rabies, caused by rabies virus (RABV), is a fatal neurological disease that still causes more than 59,000 human deaths each year. Type III interferon IFN-lambdas are cytokines with type I IFN-like antiviral activities. Although IFN-lambda can restrict the infection for some viruses, especially intestinal viruses, the inhibitory effect against RABV infection remains undefined. In this study, the function of type III IFN against RABV infection was investigated. Initially, we found that IFN-lambda2 and IFN-lambda3 could inhibit RABV replication in cells. To characterize the role of IFN-lambda in RABV infection in a mouse model, recombinant RABVs expressing murine IFN-lambda2 or IFN-lambda3, termed as rB2c-IFNlambda2 or rB2c-IFNlambda3, respectively, were constructed and rescued. It was found that expression of IFN-lambda could reduce the pathogenicity of RABV and limit viral spread in the brains by different infection routes. Furthermore, expression of IFN-lambda could induce the activation of the JAK-STAT pathway, resulting in the production of interferon-stimulated genes (ISGs). It was also found that rRABVs expressing IFN-lambda could reduce the production of inflammatory cytokines in primary astrocytes and microgila cells, restrict the opening of the blood-brain barrier (BBB), and prevent excessive infiltration of inflammatory cells into the brain, which could be responsible for the neuronal damage caused by RABV. Consistently, IFN-lambda was found to maintain the integrity of tight junction (TJ) protein ZO-1 of BBB to alleviate neuroinflammation in a transwell model. Our study underscores the role of IFN-lambda in inhibiting RABV infection, which potentiates IFN-lambda as a possible therapeutic agent for the treatment of RABV infection.
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Viruses 2020 ; 12 (4): ä
