The study revealed the molecular mechanism of herpes virus immune escape and host natural immune regulation

The natural immune response mediated by cytoplic nucleic acids plays an important role in the process of resisting pathogen invasion, in which the phosphorylation modification of the joint protein STING and MAVS is necessary to activate the type I interferon reaction.
if the natural immune response is too weak, the host will not be able to effectively resist the invasion of pathogens;
signal paths mediated by STING and MAVS are precisely regulated? Do pathogens, especially viruses, manipulate this regulatory process? Is escape or antagonized host natural immunity conducive to the replication of the virus itself? What are the molecular mechanisms? Recently, Deng Hongyu, a researcher at the Institute of Biophysics of the Chinese Academy of Sciences, identified a negatively regulated STING and MAVS-mediated natural immune response of the host protein phosphatase PPM1G, and analyzed the kaposi sarcoma-related herpes virus (KSHV) using the interstitrin ORF33 to hold PPM1G, the molecular mechanism of immune escape.
herpes virus is an ancient family of viruses that evolved a variety of strategies to suppress the host's natural immune response to infect cells and establish persistent latent infections.
interstellar protein is a class of structural proteins specific to herpes viruses that, in addition to functioning during the assembly release phase of the late stages of virus replication, are also involved in regulating cell signaling path paths, especially immune escape, in the early stages of viral infection from the beginning.
ORF33 is an interstellar protein that is conservative in all herpes viruses, and studies have shown that ORF33 plays a key role in the assembly of herpes virus particles, but it is not clear whether it has an immune escape function.
the study found that the missing KSHV virus induced cells in ORF33 produced more IFN beta than wild viruses, and that ORF33 could be combined with STING and MAVS to inhibit STING and MAVS recruitment of IRF3 molecules.
results show that ORF33 inhibits the host's natural immune response by affecting the function of the joint proteins STING and MAVS.
, the study also found that in-cell expression orF33 significantly reduced phosphate levels in STING and MAVS.
in in-body phosphatase experiments, only purified ORF33 proteins from lactating cells reduced the phosphate levels of STING and MAVS, while primary nucleocytes expressed purified ORF33.
suggests that ORF33 may recruit and dephosphate STING and MAVS using the host protein phosphatase.
using immunopopulation-mass spectrometry, the researchers identified PPM1G, the host protein that interacts with ORF33.
in-body phosphatase experiments, the primary nucleolytic expression purification of PPM1G can directly dephosphate STING and MAVS, ORF33 can enhance the interaction between PPM1G and STING or MAVS.
these results show that ORF33 inhibits the activation of STING and MAVS by recruiting the host protein phosphatase PPM1G to dephosphorylation.
further studies have found that PPM1G inhibits the host's IFN beta response, and that knocking down and knocking out the expression of PP1MG enhances the host's defenses against DNA and RNA viruses.
shown that PPM1G is able to negatively regulate the host's natural antiviral immune response.
, the study first found that the protein phosphatase PPM1G is the host factor of negative regulation of natural antiviral immune response, and revealed a new strategy of herpes virus immune escape, namely, interstitial protein ORF33 recruits the host protein phosphatase PPM1G, dephosphorylation of STING and MAVS, thereby inhibiting the production of IFN beta and the host's antiviral response, which is conducive to virus replication.
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