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    Home > Biochemistry News > Biotechnology News > Chen Jianfeng's group collaborated to discover a new mechanism by which different chemokines regulate the binding of integrin α4β7 to HIV-1 virus

    Chen Jianfeng's group collaborated to discover a new mechanism by which different chemokines regulate the binding of integrin α4β7 to HIV-1 virus

    • Last Update: 2021-07-29
    • Source: Internet
    • Author: User
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      On July 16, the international academic journal " Signal Transduction and Targeted Therapy " ( Signal Transduction and Targeted Therapy ) published an online publication of the Chen Jianfeng Research Group of the Chinese Academy of Sciences Molecular Cell Science Excellence Innovation Center (Institute of Biochemistry and Cell Biology) and China The latest research result "Distinct chemokines selectively induce HIV-1 gp120-integrin α4β7 binding via triggering conformer-specific activation of α4β7" was completed by the team of Li Guohui and Zhang Yuebin from Dalian Institute of Chemical Physics, Dalian Institute of Chemical Physics, Academy of Sciences
    .
    The work found that specific chemokines (CCL19 and CCL25) expressed in the intestinal region can stimulate integrin α4β7 to make it in a higher activated conformation, thereby binding to the HIV-1 envelope protein gp120, and promoting the virus to intestinal T cells New mechanism of infection

    .

      After HIV (Human immunodeficiency virus, HIV) -1 virus infects the human host, it replicates in large amounts in Gut-associated lymphoid tissue (GALT), and infects CD4 + T cells to gradually deplete it, triggering acquired Acquired immune deficiency syndrome (Acquired immune deficiency syndrome, AIDS)
    .
    The envelope protein gp120 is located on the surface of the HIV-1 virus, and its binding to the receptor molecules on the surface of CD4
    + T cells is a key step for HIV-1 to infect T cells
    .
    Studies have shown that integrin α4β7 can bind to gp120, so CD4
    + T cells that highly express GALT homing adhesion molecule α4β7 are more susceptible to HIV-1 infection, but how the binding of α4β7 and gp120 is regulated in vivo is still unclear
    .

      Chen Jianfeng's team found that inactive integrin α4β7 cannot bind to gp120, and only when integrin α4β7 is highly activated can it bind to gp120
    .
    The binding of integrin α4β7 to gp120 depends on the interaction between the highly conserved tripeptide sequence LDI in gp120 and the MIDAS (Metal ion-dependent adhesion site) in the integrin β7 subunit

    .
    Among the chemokines such as CCL5, CXCL10, CCL19 and CCL25 expressed in intestinal tissues, only the integrin α4β7 activated by CCL19 and CCL25 can bind to gp120

    .
    Further molecular mechanism studies have found that the stimulation of different chemokines makes integrins in different activation states

    .
    The stimulation of CCL19 and CCL25 will cause integrin α4β7 to have a relatively stretched activated conformation, which can bind to gp120; while CCL5 and CXCL10 stimulated integrin α4β7 has a less stretched activated conformation, which cannot bind to gp120

    .
    In addition, we also found that the combination of gp120 and integrin α4β7 activates multiple intracellular signaling pathways, which may regulate virus replication and T cell function

    .

      In summary, this study reveals that specific chemokines in the intestine can promote the binding of α4β7 and HIV-1 virus gp120 by causing a specific activation conformation of integrin α4β7, and activate multiple intracellular signaling pathways, ultimately promoting HIV -1 infection of T cells
    .
    This research may provide new ideas for the treatment of AIDS and the screening of related drugs

    .

      Researcher Chen Jianfeng from the Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences is the corresponding author, researcher Li Guohui and Associate Researcher Zhang Yuebin from Dalian Institute of Chemical Physics, Chinese Academy of Sciences are the co-corresponding authors, and Dr.
    Shu Wang and Associate Researcher Lin Changdong from the Center for Molecular Cellular Excellence are the co-first authors

    .
    The research was awarded by the National Natural Science Foundation of China, the Ministry of Science and Technology, the Chinese Academy of Sciences, the Shanghai Academic Leaders Project, the Chinese Academy of Sciences Youth Innovation Promotion Association, the Chinese Association for Science and Technology "Young Talents Project" and Sanofi-Chinese Academy of Sciences Shanghai Life Science Research Institute (SA-SIBS) Outstanding Young Talents Award Fund and other funding

    .
    This research is strongly supported by the Cell Analysis Technology Platform and Molecular Biology Technology Platform of the Center of Excellence for Molecular Cells

    .
    Special thanks to Professor Brian Seed and Dr.
    Slim Sassi of Massachusetts General Hospital in the United States for providing the codon-optimized MN gp120 expression plasmid; Professor Lu Lu and Master Cao Miao of Fudan University for providing the expression plasmids of BG505 SOSIP.
    664, Furin and PGT145

    .

      Article link: https://#Sec1

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