Biology subjects

Chan, J. F.-W.

Publications and source records attributed to Chan, J. F.-W..

2 recordsLinked to original sources

bioRxiv2020

SARS-CoV-2 spike D614G variant exhibits highly efficient replication and transmission in hamsters

SARS-CoV-2 causes disease varying in severity from asymptomatic infections to severe respiratory distress and death in humans. The viral factors which determine transmissibility and pathogenicity are not yet clearly characterized. We used the hamster infection model to compare the replication ability and pathogenicity of five SARS-CoV-2 strains isolated from early cases originating in Wuhan, China, in February, and infected individuals returning from Europe and elsewhere in March 2020. The HK-13 and HK-95 isolates showed distinct pathogenicity in hamsters, with higher virus titers and more severe pathological changes in the lungs observed compared to other isolates. HK-95 contains a D614G substitution in the spike protein and demonstrated higher viral gene expression and transmission efficiency in hamsters. Intra-host diversity analysis revealed that further quasi species were generated during hamster infections, indicating that strain-specific adaptive mutants with advantages in replication and transmission will continue to arise and dominate subsequent waves of SARS-CoV-2 dissemination.

microbiology↗

bioRxiv2020

NLRP3 inflammasome contributes to host defense against Talaromyces marneffei infection

Talaromyces marneffei is an important thermally dimorphic pathogen causing disseminated mycoses in immunocompromised individuals in southeast Asia. Previous study has suggested that NLRP3 inflammasome plays a critical role in antifungal immunity. However, the mechanism underlying the role of NLRP3 inflammasome activation in host defense against T. marneffei remains unclear. We show that T. marneffei yeasts but not conidia induce potent IL-1{beta} response, which is differentially regulated in discrete immune cell types. Dectin-1/Syk signaling pathway mediates pro-IL-1{beta} production, and NLRP3 inflammasome is activated to trigger the processing of pro-IL-1{beta} into IL-1{beta}. The activated NLRP3 inflammasome partially promotes Th1 and Th17 immune responses against T. marneffei yeasts. In vivo, mice with NLRP3 or caspase-1 deficiency exhibit higher mortality rate and fungal load compared to wild-type mice. Herein, our study provides the first evidence that NLRP3 inflammasome contributes to host defense against T. marneffei infection, which may have implications for future antifungal therapeutic designs.

microbiology↗