Li Chen

Soluble host factors in the upper respiratory tract can serve as the first line of defense against SARS-CoV-2 infection. In this study, we described the identification and function of a human airway trypsin–like protease (HAT), capable of reducing the infectivity of ancestral SARS-CoV-2. Further, in mouse models, HAT analogue expression was upregulated by SARS-CoV-2 infection. The antiviral activity of HAT functioned through the cleavage of the SARS-CoV-2 spike glycoprotein at R682. This cleavage resulted in inhibition of the attachment of ancestral spike proteins to host cells, which inhibited the cell-cell membrane fusion process. Importantly, exogenous addition of HAT notably reduced the infectivity of ancestral SARS-CoV-2 in vivo. However, HAT was ineffective against the Delta variant and most circulating Omicron variants, including the BQ.1.1 and XBB.1.5 subvariants. We demonstrate that the P681R mutation in Delta and P681H mutation in the Omicron variants, adjacent to the R682 cleavage site, contributed to HAT resistance. Our study reports what we believe to be a novel soluble defense factor against SARS-CoV-2 and resistance of its actions in the Delta and Omicron variants.

The relationship between chronic inflammation and neoplastic diseases is not fully understood. The inflammatory microenvironment of a tumor is an intricate network that consists of numerous types of cells, cytokines, enzymes and signaling pathways. Recent evidence shows that the crucial components of cancer-related inflammation are involved in a coordinated system to influence the development of cancer, which may shed light on the development of potential anticancer therapies. Since the last century, considerable effort has been devoted to developing gene therapies for life-threatening diseases. When it comes to modulating the inflammatory microenvironment for cancer therapy, inflammatory cytokines are the most efficient targets. In this manuscript, we provide a comprehensive review of the relationship between inflammation and cancer development, especially focusing on inflammatory cytokines. We also summarize the clinical trials for gene therapy targeting inflammatory cytokines for cancer treatment. Future perspectives concerned with new gene-editing technology and novel gene delivery systems are finally provided.