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Zheng, Z.-Z.

Publications and source records attributed to Zheng, Z.-Z..

2 recordsLinked to original sources

Lithocholic acid phenocopies rejuvenating and life-extending effects of calorie restriction

Calorie restriction (CR) is a dietary intervention to promote health and longevity. CR causes various metabolic changes in both the production and circulation of metabolites; however, it remains unclear which of the changed metabolite(s) can account for the physiological benefits of CR. Through metabolomic analysis of metabolites undergoing abundance changes during CR and subsequent functional validation, we found that lithocholic acid (LCA) is the only metabolite that alone can recapitulate the effects of CR, including activation of AMPK and the rejuvenating effects of muscle regeneration, grip strength and running capacity in mice. Interestingly, LCA also activates AMPK and exerts life- and health-extending effects in Caenorhabditis elegans and Drosophila melanogaster, indicating that these animal models are able to transmit the signalling of LCA once administered. Knockout of AMPK abrogates LCA-induced phenotypes, in nematodes and flies, as well as in mice. Together, we have identified that administration of the CR-upregulated metabolite LCA alone can confer anti-ageing benefits to metazoans, in an AMPK-dependent manner.

physiology↗

New efficient intercellular spread mode of respiratory syncytial virus contributes to neutralization escape and persistence

There is no licensed vaccine or therapeutic antibody for respiratory syncytial virus (RSV). The induction of high-titer, potent neutralizing antibodies cannot completely inhibit breakthrough infection and enhanced respiratory disease (ERD), encouraging a focus on the relationship between virus intercellular spread and neutralizing antibodies. By blocking the known intercellular spread modes and with the aid of ultrahigh-resolution imaging, we observed a new efficient mode of intercellular spread in which RSV-infected cells directly transfer viral materials (including viral replication factories) to neighboring cells through protruding open-ended microfilament-rich intercellular nanotubes. The new mode is virion-independent and antibody-insensitive, beginning as early as 3 h post infection. Furthermore, replication-defective viral genomes (DVGs) might also utilize the new mode, facilitating the establishment of latent viral infections. Therefore, our data provide a new perspective on RSV cell-to-cell spread and might help to explain the immune escape and latent persistence of paramyxoviruses.

microbiology↗