BACKGROUND Congenital agenesis of the gallbladder(CAGB)is a rare condition often misdiagnosed as cholecystolithiasis,leading to unnecessary surgeries.Accurate diagnosis and surgical exploration are crucial in patients...BACKGROUND Congenital agenesis of the gallbladder(CAGB)is a rare condition often misdiagnosed as cholecystolithiasis,leading to unnecessary surgeries.Accurate diagnosis and surgical exploration are crucial in patients with suspected CAGB or atypical gallbladder stone symptoms.Preoperative imaging,such as magnetic resonance cholangiopancreatography(MRCP),plays a vital role in confirming the diagnosis.Careful intraoperative dissection is necessary to avoid iatrogenic injuries and misdiagnosis.Multidisciplinary consultations and collaboration,along with the use of various diagnostic methods,can minimize associated risks.CASE SUMMARY We present the case of a 34-year-old female with suspected gallbladder stones,ultimately diagnosed with CAGB through surgical exploration.The patient underwent laparoscopic examination followed by open exploratory surgery,which confirmed absence of the gallbladder.Subsequent imaging studies supported the diagnosis.The patient received appropriate postoperative care and experienced a successful recovery.CONCLUSION This case highlights the rarity of CAGB and the importance of considering this condition in the differential diagnosis of patients with gallbladder stone symptoms.Accurate diagnosis using preoperative imaging,such as MRCP,is crucial to prevent unnecessary surgeries.Surgeons should exercise caution and conduct meticulous dissection during surgery to avoid iatrogenic injuries and ensure accurate diagnosis.Multidisciplinary collaboration and utilization of various diagnostic methods are essential to minimize the risk of misdiagnosis.Selection of the optimal treatment strategy should prioritize minimizing trauma and maintaining open communication with the patient and their family members.展开更多
Hantaan virus(HTNV)is a rodent-borne virus that causes hemorrhagic fever with renal syndrome(HFRS),resulting in a high mortality rate of 15%.Interferons(IFNs)play a critical role in the anti-hantaviral immune response...Hantaan virus(HTNV)is a rodent-borne virus that causes hemorrhagic fever with renal syndrome(HFRS),resulting in a high mortality rate of 15%.Interferons(IFNs)play a critical role in the anti-hantaviral immune response,and IFN pretreatment efficiently restricts HTNV infection by triggering the expression of a series of IFNstimulated genes(ISGs)through the Janus kinase-signal transducer and activator of transcription 1(JAK-STAT)pathway.However,the tremendous amount of IFNs produced during late infection could not restrain HTNV replication,and the mechanism remains unclear.Here,we demonstrated that receptor-interacting protein kinase 3(RIPK3),a crucial molecule that mediates necroptosis,was activated by HTNV and contributed to hantavirus evasion of IFN responses by inhibiting STAT1 phosphorylation.RNA-seq analysis revealed the upregulation of multiple cell death-related genes after HTNV infection,with RIPK3 identified as a key modulator of viral replication.RIPK3 ablation significantly enhanced ISGs expression and restrained HTNV replication,without affecting the expression of pattern recognition receptors(PRRs)or the production of type I IFNs.Conversely,exogenously expressed RIPK3 compromised the host's antiviral response and facilitated HTNV replication.RIPK3^(-/-)mice also maintained a robust ability to clear HTNV with enhanced innate immune responses.Mechanistically,we found that RIPK3 could bind STAT1 and inhibit STAT1 phosphorylation dependent on the protein kinase domain(PKD)of RIPK3 but not its kinase activity.Overall,these observations demonstrated a noncanonical function of RIPK3 during viral infection and have elucidated a novel host innate immunity evasion strategy utilized by HTNV.展开更多
Hantaan virus(HTNV),the prototype virus of hantavirus,could escape innate immunity by restraining type I interferon(IFN)responses.It is largely unknown whether there existed other efficient anti-hantaviral tactics in ...Hantaan virus(HTNV),the prototype virus of hantavirus,could escape innate immunity by restraining type I interferon(IFN)responses.It is largely unknown whether there existed other efficient anti-hantaviral tactics in host cells.Here,we demonstrate that the stimulator of interferon genes(STING)strengthens the host IFNindependent anti-hantaviral immunity.HTNV infection activates RIG-I through IRE1-XBP 1-mediated ER stress,which further facilitates the subcellular translocation and activation of STING.During this process,STING triggers cellular autophagy by interacting with Rab7A,thus restricting viral replication.To note,the anti-hantaviral effects of STING are independent of canonical IFN signaling.Additionally,neither application of the pharmacological antagonist nor the agonist targeting STING could improve the outcomes of nude mice post HTNV challenge in vivo.However,the administration of plasmids exogenously expressing the mutant C-terminal tail(ΔCTT)STING,which would not trigger the type I IFN responses,protected the nude mice from lethal HTNV infection.In summary,our research revealed a novel antiviral pathway through the RIG-I-STING-autophagy pathway,which offered novel therapeutic strategies against hantavirus infection.展开更多
文摘BACKGROUND Congenital agenesis of the gallbladder(CAGB)is a rare condition often misdiagnosed as cholecystolithiasis,leading to unnecessary surgeries.Accurate diagnosis and surgical exploration are crucial in patients with suspected CAGB or atypical gallbladder stone symptoms.Preoperative imaging,such as magnetic resonance cholangiopancreatography(MRCP),plays a vital role in confirming the diagnosis.Careful intraoperative dissection is necessary to avoid iatrogenic injuries and misdiagnosis.Multidisciplinary consultations and collaboration,along with the use of various diagnostic methods,can minimize associated risks.CASE SUMMARY We present the case of a 34-year-old female with suspected gallbladder stones,ultimately diagnosed with CAGB through surgical exploration.The patient underwent laparoscopic examination followed by open exploratory surgery,which confirmed absence of the gallbladder.Subsequent imaging studies supported the diagnosis.The patient received appropriate postoperative care and experienced a successful recovery.CONCLUSION This case highlights the rarity of CAGB and the importance of considering this condition in the differential diagnosis of patients with gallbladder stone symptoms.Accurate diagnosis using preoperative imaging,such as MRCP,is crucial to prevent unnecessary surgeries.Surgeons should exercise caution and conduct meticulous dissection during surgery to avoid iatrogenic injuries and ensure accurate diagnosis.Multidisciplinary collaboration and utilization of various diagnostic methods are essential to minimize the risk of misdiagnosis.Selection of the optimal treatment strategy should prioritize minimizing trauma and maintaining open communication with the patient and their family members.
基金This work was supported in whole or in part by the National Natural Science Foundation of China(82172272,31970148 and 82222367)the Key Research and Development Program of Shaanxi(2021ZDLSF01-05 and 2021ZDLSF01-02).
文摘Hantaan virus(HTNV)is a rodent-borne virus that causes hemorrhagic fever with renal syndrome(HFRS),resulting in a high mortality rate of 15%.Interferons(IFNs)play a critical role in the anti-hantaviral immune response,and IFN pretreatment efficiently restricts HTNV infection by triggering the expression of a series of IFNstimulated genes(ISGs)through the Janus kinase-signal transducer and activator of transcription 1(JAK-STAT)pathway.However,the tremendous amount of IFNs produced during late infection could not restrain HTNV replication,and the mechanism remains unclear.Here,we demonstrated that receptor-interacting protein kinase 3(RIPK3),a crucial molecule that mediates necroptosis,was activated by HTNV and contributed to hantavirus evasion of IFN responses by inhibiting STAT1 phosphorylation.RNA-seq analysis revealed the upregulation of multiple cell death-related genes after HTNV infection,with RIPK3 identified as a key modulator of viral replication.RIPK3 ablation significantly enhanced ISGs expression and restrained HTNV replication,without affecting the expression of pattern recognition receptors(PRRs)or the production of type I IFNs.Conversely,exogenously expressed RIPK3 compromised the host's antiviral response and facilitated HTNV replication.RIPK3^(-/-)mice also maintained a robust ability to clear HTNV with enhanced innate immune responses.Mechanistically,we found that RIPK3 could bind STAT1 and inhibit STAT1 phosphorylation dependent on the protein kinase domain(PKD)of RIPK3 but not its kinase activity.Overall,these observations demonstrated a noncanonical function of RIPK3 during viral infection and have elucidated a novel host innate immunity evasion strategy utilized by HTNV.
基金supported by grants from the National Natural Science Foundation of China (No.31970148,82172272 and 82202367)the Key Research and Development Program of Shaanxi (2021ZDLSF01-02 and 2021ZDLSF01-05).
文摘Hantaan virus(HTNV),the prototype virus of hantavirus,could escape innate immunity by restraining type I interferon(IFN)responses.It is largely unknown whether there existed other efficient anti-hantaviral tactics in host cells.Here,we demonstrate that the stimulator of interferon genes(STING)strengthens the host IFNindependent anti-hantaviral immunity.HTNV infection activates RIG-I through IRE1-XBP 1-mediated ER stress,which further facilitates the subcellular translocation and activation of STING.During this process,STING triggers cellular autophagy by interacting with Rab7A,thus restricting viral replication.To note,the anti-hantaviral effects of STING are independent of canonical IFN signaling.Additionally,neither application of the pharmacological antagonist nor the agonist targeting STING could improve the outcomes of nude mice post HTNV challenge in vivo.However,the administration of plasmids exogenously expressing the mutant C-terminal tail(ΔCTT)STING,which would not trigger the type I IFN responses,protected the nude mice from lethal HTNV infection.In summary,our research revealed a novel antiviral pathway through the RIG-I-STING-autophagy pathway,which offered novel therapeutic strategies against hantavirus infection.
