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Distinct Functions of Bombyx mori Peptidoglycan Recognition Protein 2 in Immune Responses to Bacteria and Viruses
Liang Jiang1,2, Weiqiang Liu1, Huizhen Guo1,2
1Biological Science Research Center, Southwest University, Chongqing, China.
Abstract:
Peptidoglycan recognition protein (PGRP) is an important pattern recognition receptor in innate immunity that is vital for bacterial recognition and defense in insects. Few studies report the role of PGRP in viral infection. Here we cloned two forms of PGRP from the model lepidopteran Bombyx mori: BmPGRP2-1 is a transmembrane protein, whereas BmPGRP2-2 is an intracellular protein. BmPGRP2-1 bound to diaminopimelic acid (DAP)-type peptidoglycan (PGN) to activate the canonical immune deficiency (Imd) pathway. BmPGRP2-2 knockdown reduced B. mori nucleopolyhedrovirus (BmNPV) multiplication and mortality in cell lines and in silkworm larvae, while its overexpression increased viral replication. Transcriptome and quantitative PCR (qPCR) results confirmed that BmPGRP2 negatively regulated phosphatase and tensin homolog (PTEN). BmPGRP2-2 expression was induced by BmNPV, and the protein suppressed PTEN-phosphoinositide 3-kinase (PI3K)/Akt signaling to inhibit cell apoptosis, suggesting that BmNPV modulates BmPGRP2-2-PTEN-PI3K/Akt signaling to evade host antiviral defense. These results demonstrate that the two forms of BmPGRP2 have different functions in host responses to bacteria and viruses.
Insights
Peptidoglycan recognition protein 2 (PGRP2) in silkworms has distinct roles. One form aids bacterial defense, while the other aids viral replication by inhibiting apoptosis.
Area of Science:
- Insect immunity
- Molecular biology
- Virology
Background:
- Peptidoglycan recognition proteins (PGRPs) are key in insect innate immunity against bacteria.
- The role of PGRPs in viral infections remains largely unexplored.
- Two PGRP forms, BmPGRP2-1 and BmPGRP2-2, were identified in Bombyx mori.
Purpose of the Study:
- To investigate the distinct functions of BmPGRP2-1 and BmPGRP2-2 in Bombyx mori.
- To elucidate the role of BmPGRP2 in viral infection and host defense mechanisms.
- To understand the interaction between BmPGRP2, PTEN, and PI3K/Akt signaling in viral evasion.
Main Methods:
- Cloning of BmPGRP2-1 and BmPGRP2-2 from Bombyx mori.
- Diaminopimelic acid (DAP)-type peptidoglycan (PGN) binding assays.
- RNA interference (RNAi) for BmPGRP2-2 knockdown and gene overexpression studies.
- Bombyx mori nucleopolyhedrovirus (BmNPV) infection assays in cell lines and silkworm larvae.
- Transcriptome analysis and quantitative PCR (qPCR) for gene expression.
- Western blotting to assess protein levels and signaling pathway activation.
Main Results:
- BmPGRP2-1 binds DAP-type PGN and activates the immune deficiency (Imd) pathway.
- BmPGRP2-2 knockdown reduces BmNPV multiplication and mortality, while overexpression enhances viral replication.
- BmPGRP2 negatively regulates phosphatase and tensin homolog (PTEN) expression.
- BmNPV infection induces BmPGRP2-2 expression, which suppresses PTEN-PI3K/Akt signaling to inhibit apoptosis.
- BmNPV appears to modulate the BmPGRP2-2-PTEN-PI3K/Akt pathway to evade host antiviral responses.
Conclusions:
- BmPGRP2-1 and BmPGRP2-2 exhibit differential functions in response to bacterial and viral pathogens.
- BmPGRP2-2 plays a pro-viral role by inhibiting host cell apoptosis through the PTEN-PI3K/Akt pathway.
- Bombyx mori utilizes BmPGRP2-2 as a target for viral evasion strategies, highlighting a novel interaction in insect antiviral immunity.
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