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    Home > Biochemistry News > Biotechnology News > Wuhan Institute of Virology et al. revealed that P26/poxin protein has the dual function of inhibiting two natural immune response pathways, extracellular and intracellular

    Wuhan Institute of Virology et al. revealed that P26/poxin protein has the dual function of inhibiting two natural immune response pathways, extracellular and intracellular

    • Last Update: 2023-01-05
    • Source: Internet
    • Author: User
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    In November 2022, the international academic journal Nature Communications published online the latest results of the collaborative team of Wang Manli, Hu Zhihong, Gong Peng of Wuhan Institute of Virology, Chinese Academy of Sciences/Zou Zhen, Institute of Zoology, Chinese Academy of Sciences, with the paper "Dual roles and evolutionary implications of P26/poxin in antagonizing intracellular.
    " cGAS-STING and extracellular melanization immunity”(doi:10.
    1038/s41467-022-34761-0)
    。 The study found that the P26/poxin protein, which is widely present in poxvirus, insect virus, lepidopteran insects and hymenoptera parasitic wasps, has the dual function
    of inhibiting both the host's extracellular and intracellular innate immunity.

    In 2019, an article published in Nature reported that poxin, a nuclease encoded by the pox virus, can inhibit the intracellular cGAS-STING immune pathway
    by hydrolyzing 2′,3′-cGAMP.
    However, some insect viruses and the poxin homolog P26 of the insect host predict signaling peptides and potential protease activity sites, speculating that it may play a role
    in antagonizing extracellular antiviral innate immunity.
    The blackening reaction is an important extracellular innate immune response that is ubiquitous in insects and plays an important role
    in fighting off microbial infections.
    The collaborative team revealed that baculovirus infection can inhibit the blackening response of bollworm (Yuan et al.
    , 2017, PLoS Pathogens); and revealed two independent blackening cascade pathways in bollworm (Wang et al.
    , 2020, Front Immunol; Wang et al.
    , 2022, Insect Biochem Mol Biol)
    。 Proteomics studies have found that bollworm virus P26 is highly expressed in post-infection insect hemolymph, so it is speculated that P26 may mediate viral inhibition of host blackening response
    .

    The team found that the P26 of bollworm virus can effectively inhibit the blackening reaction in in vitro biochemical experiments; Knocking out the p26 gene causes the virus to lose the inhibition activity of the blackening response; The target of P26 is procSPH11/procSPH50
    , an important cofactor in the blackening pathway.
    The team also resolved the high-resolution crystal structure of the P26 protein, and mutational analysis of key sites showed that viral nucleases and active sites that inhibit the blackening reaction are located on
    different domains.
    The study found that a variety of secreted P26/poxin from parasitic wasps and different baculoviruses generally had the dual functions
    of inhibiting extracellular blackening and inhibiting the intracellular cGAS-STING pathway.

    This study reveals for the first time that P26/poxin evolved the dual functions of inhibiting extracellular blackening and intracellular cGAS-STING immune pathway in the long-term co-evolution of the virus-host, which enriched the understanding
    of the important biological functions of P26/poxin homologous protein.


    Figure: P26/poxin dual functional pattern of inhibition of intracellular and extracellular innate immune responses

    Yin Mengyi, a doctoral student at the Wuhan Institute of Virology, and Kuang Wenhua, an assistant researcher, are co-first authors
    of the paper.
    Researcher Wang Manli, researcher Hu Zhihong and researcher Gong Peng of the Biosafety Big Science Center of Wuhan Institute of Virology, and researcher Zou Zhen of the Institute of Zoology are co-corresponding authors
    of the paper.
    The research was supported
    by the Strategic Pilot Research Project of the Chinese Academy of Sciences, the National Natural Science Foundation of China, and the Hubei Provincial Natural Science Outstanding Youth Fund.

    Article Links:
    1.
    Dual roles and evolutionary implications of P26/poxin in antagonizing intracellular cGAS-STING and extracellular melanization immunity | Nature Communications

    2.
    Inhibition of melanization by serpin-5 and serpin-9 promotes baculovirus infection in cotton bollworm Helicoverpa armigera - PubMed (nih.
    gov)

    3.
    Identification of a Conserved Prophenoloxidase Activation Pathway in Cotton Bollworm Helicoverpa armigera -PubMed (nih.
    gov)

    4.
    The Micrococcus luteus infection activates a novel melanization pathway of cSP10, cSP4, and cSP8 in Helicoverpa armigera - PubMed (nih.
    gov) 
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