Coxsackievirus group B3 regulates ASS1-mediated metabolic reprogramming and promotes macrophage inflammatory polarization in viral myocarditis.

ABSTRACT: Coxsackievirus group B3 (CVB3) belongs to the genus Enteroviruses of the family Picornaviridae and is the main pathogen underlying viral myocarditis (VMC). No specific therapeutic is available for this condition. Argininosuccinate synthase 1 (ASS1) is a key enzyme in the urea cycle that converts citrulline and aspartic acid to argininosuccinate. Here, we found that CVB3 and its capsid protein VP2 inhibit the autophagic degradation of ASS1 and that CVB3 consumes citrulline to upregulate ASS1, triggers urea cycle metabolic reprogramming, and then activates macrophages to develop pro-inflammatory polarization, thereby promoting the occurrence and development of VMC. Conversely, citrulline supplementation to prevent depletion can downregulate ASS1, rescue macrophage polarization,

SUBMITTER: Liu Q 

PROVIDER: S-EPMC11406948 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature