JEM: Uncovering the molecular mechanism of herpes simplex virus to evade host immune system infection of the brain

2020 May 13 News /BioValleyBIOON / - herpes simplex virus (HSV1, Herpessimplexvirus) infection starts at the mucosal surface of the body, HSV1 will mucosal the surface of infected epithelial cells, when it spread from the peripheral nerves to the central nervous system, it will infect the brain and cause herpes simplex encephalitis (herpessimplexencephalitis), which is a rare disease, if not treated higher mortality rate; in many cases , patients can inhibit the body's innate immune system HSV1 infection of the brain, but sometimes HSV1 avoid brain defense mechanismSource:CC0PublicDomainRecently, one published in the International Journal ofJournalofExperimentalMedicineresearch report from Aarhus University and other institutions of the Andean scientists through research reveals the brain to help HSV1 infection of molecular mechanismsThe researchers said interferon gene stimulating protein (STING, stimulatorofinterferongenes) plays a key role in the body's immune system play in, DNA virus which can be activated during viral infection, then STING will open cell cascade effect helps the body to resist the invadersThese effects include gene activation and start production of cytokines to enhance the immune response proteins (IFN, a type I interferon) isresearchers say, HSV1 can produce a variety of mechanisms to evade a host to induce type 1 IFN's, but they do not know how to avoid the type 1 IFN HSV1 reactions in the brainIn this study, researchers identify HSV1 genome of a particular viral protein can promote the immune evasion brain, the researchers used as gene deletion key or critical HSV1 mutant gene is altered mouse brain infected cultures body when cells, they found that a gene mutation VP1-2 HSV1 body can show increased innate immune response, the mice can be exhibited against HSV1 mutant carrying VP1-2 similar strong immunity, suggesting that, VP1-2 gene inhibits the normal host organism's immune systemThe key difference between the normal and mutantVP1-2 gene is mutated such that the gene is lost the ability to remove the virus infected cells other proteins inside the cell posttranslational modifications (ubiquitination) of the pan biotinylated latter translational modification mechanisms, which can regulate the immune response cascade STING, the researchers found that, VP1-2 capable of targeting brain immune cells (microglia) STING activity, in addition, VP1-2 can simply remove the ubiquitination STING thereby can be suppressed STING is activated to emit a signalPrior research paper, the researchers also do not know how the virus is to change the ubiquitination of brain immune responsesBodda researchers said this paper shows that, HSV1 capable of targeting ubiquitination of the brain to promote STING HIV infection and progression to herpes simplex encephalitis, inhibition of virus removal capability ubiquitination special drugs can promote brain cells to produce effective anti-viral response to protect against HSV1, which for severe immune function defect in patients with HSV1 infection of the brain is very important, especially in patients who have been resistant to standard therapy acyclovir Finally the researchers note that, although the study focused on the herpes virus, but for such as SARS-CoV-2-induced COVID-19 also has applied significance, the researchers believe that if they can inhibit viral resistance STING off, then, can effectively suppress viral replication, which perhaps is the late stage of development to treat herpes virus, influenza virus coronavirus infection and even new therapy offers a new way of thinking (Biovalley Bioon.com) Original source: ChiranjeeviBodda, LineS.Reinert, StefanieFruhwürth, etal HSV1VP1-2deubiquitinatesSTINGtoblocktypeIinterferonexpressionandpromotebraininfection ,
JournalofExperimentalMedicine (2020) .DOI: 10.1084 / jem.20191422