Biology subjects

Chen, Z.-S.

Publications and source records attributed to Chen, Z.-S..

3 recordsLinked to original sources

bioRxiv2024

Influenza A Virus H7 nanobody recognizes a conserved immunodominant epitope on hemagglutinin head and confers heterosubtypic protection

Influenza remains a persistent global health challenge, largely due to the virus continuous antigenic drift and shift, which impede the development of a universal vaccine. To address this, the identification of broadly neutralizing antibodies and their epitopes is crucial. Nanobodies, with their unique characteristics and binding capacity, offer a promising avenue to identify such epitopes. Here, we isolated and purified a hemagglutinin (HA)-specific nanobody that recognizes an H7 subtype of influenza A virus. Notably, the nanobody, named E10, exhibited broad-spectrum binding, cross-group neutralization and in vivo protection across various influenza A subtypes. Through phage display and in vitro characterization, we demonstrated that E10 specifically targets an epitope on HA head. This epitope is part of the conserved lateral patch of HA head and proved to be highly immunodominant upon H7 infection. Importantly, immunization with a peptide including the E10 epitope elicited cross-reactive antibodies and mediated partial protection from lethal viral challenge. Our data highlight the potential of E10 and its associated epitope as a candidate for future influenza prevention strategies.

microbiology↗

bioRxiv2024

The triose phosphate/phosphate translocator exports photosynthetic glyceraldehyde 3-phosphate from chloroplasts to trigger antimicrobial immunity in plants.

Chloroplasts play a crucial role in plant immunity against invading microbes. However, it remains poorly understood whether photosynthetic metabolites from chloroplasts participate directly in host defenses. Here, we uncovered Arabidopsis thalinana triose phosphate/phosphate translocator (AtTPT), a known translocator for chloroplast inner membrane, plays an indispensable role in suppressing virus infection and evoking defense responses. Interestingly, overexpression of AtTPT impairs virus accumulation in plants, while loss-of-function tpt3 mutants exhibit an increased viral load. The antiviral activity of AtTPT requires its phosphate transport capacity, implying that it actually functions through its metabolite(s). To this end, we found that glyceraldehyde 3-phosphate (GAP), one of AtTPTs translocated metabolites, can drastically enhance expression of defense-related genes and prominently induce defense signaling pathways. More excitingly, AtTPT or GAP robustly restricts the proliferation of multiple types of phytopathogens. Collectively, we propose that AtTPT exports GAP to mediate broad-spectrum resistance to pathogens, which provides new insights into the mechanism underlying the chloroplast-mediated immunity by a photosynthetic metabolite.

plant biology↗

bioRxiv2019

Fexofenadine inhibits TNF signaling through targeting to cytosolic phospholipase A2 and is therapeutic against autoimmune diseases

TNF- signaling plays a central role in the pathogenesis of various diseases, particularly autoimmune diseases. Screening of a library composed of FDA approved drugs led to the identification of Terfenadine and its active metabolite Fexofenadine as inhibitors of TNF- signaling. Both Fexofenadine and Terfenadine inhibited TNF/NF-{kappa}B signaling in vitro and in vivo, and ameliorated disease symptoms in various autoimmune disease models, including TNF- transgenic mice, collagen-induced arthritis, and inflammatory bowel disease. Subsequent studies identified cytosolic phospholipase A2 (cPLA2) as a novel target of Fexofenadine. Fexofenadine blocked TNF-stimulated cPLA2 activity and arachidonic acid production through binding to catalytic domain 2 of cPLA2 and inhibition of its phosphorylation on Ser-505. Further, deletion of cPLA2 abolished Fexofenadines anti-TNF activity. Collectively, these findings not only provide new insights into the understanding of Fexofenadine action and underlying mechanism, but also provide new therapeutic interventions for various TNF- and cPLA2-associated pathologies and conditions, particularly autoimmune diseases.

molecular biology↗