AUTHOR=Feng Yu-ting , Yang Chun-yan , Wu Lin , Wang Yuan-cheng , Shen Guan-wang , Lin Ping 

TITLE=BmSPP is a virus resistance gene in Bombyx mori

JOURNAL=Frontiers in Immunology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1377270

DOI=10.3389/fimmu.2024.1377270

ISSN=1664-3224

ABSTRACT=<sec><title>Introduction</title><p>Signal peptide peptidase (<italic>SPP</italic>) is an intramembrane protease involved in a variety of biological processes, it participates in the processing of signal peptides after the release of the nascent protein to regulate the endoplasmic reticulum associated degradation (ERAD) pathway, binds misfolded membrane proteins, and aids in their clearance process. Additionally, it regulates normal immune surveillance and assists in the processing of viral proteins. Although <italic>SPP</italic> is essential for many viral infections, its role in silkworms remains unclear. Studying its role in the silkworm, <italic>Bombyx mori</italic> , may be helpful in breeding virus-resistant silkworms.</p></sec><sec><title>Methods</title><p>First, we performed RT-qPCR to analyze the expression pattern of <italic>BmSPP</italic>. Subsequently, we inhibited <italic>BmSPP</italic> using the <italic>SPP</italic> inhibitor 1,3-di-(N-carboxybenzoyl-L-leucyl-L-leucylaminopropanone ((Z-LL)<sub>2</sub>-ketone) and downregulated the expression of <italic>BmSPP</italic> using CRISPR/Cas9 gene editing. Furthermore, we assessed the impact of these interventions on the proliferation of <italic>Bombyx mori</italic> nucleopolyhedrovirus (BmNPV).</p></sec><sec><title>Results</title><p>We observed a decreased in the expression of <italic>BmSPP</italic> during viral proliferation. It was found that higher concentration of the inhibitor resulted in greater inhibition of BmNPV proliferation. The down-regulation of <italic>BmSPP</italic> in both in vivo and in vitro was found to affect the proliferation of BmNPV. In comparison to wild type silkworm, <italic>BmSPP<sup>KO</sup></italic> silkworms exhibited a 12.4% reduction in mortality rate.</p></sec><sec><title>Discussion</title><p>Collectively, this work demonstrates that <italic>BmSPP</italic> plays a negative regulatory role in silkworm resistance to BmNPV infection and is involved in virus proliferation and replication processes. This finding suggests that <italic>BmSPP</italic> servers as a target gene for BmNPV virus resistance in silkworms and can be utilized in resistance breeding programs.</p></sec>