Allicin, an antioxidant, is known for providing garlic with its unique fragrance and taste, as well as for its antimicrobial properties. Black garlic, a fermented form of garlic, contains higher levels of antioxidants...Allicin, an antioxidant, is known for providing garlic with its unique fragrance and taste, as well as for its antimicrobial properties. Black garlic, a fermented form of garlic, contains higher levels of antioxidants than fresh garlic. Antioxidants play a vital role in alleviating cellular stress during viral infections. Viral infections result in oxidative stress through the production of reactive oxidative species (ROS). A prolonged state of oxidative stress can result in cell death, DNA damage, and disease progression. In this study, black garlic extract (BGE) is evaluated for its ability to mitigate cytopathic effects and oxidative stress caused by herpes simplex virus-2 (HSV-2) infections in vitro. Antiviral assays were performed to determine the percent of viral inhibition resulting from treatment with the BGE. ROS-Glo<sup>TM</sup> H<sub>2</sub>O<sub>2</sub> assays were then completed to measure the post-infection ROS levels of BGE-treated virus and cells. The results thus far suggest that BGE may inhibit viral infection and decrease levels of oxidative stress.展开更多
AIM: To investigate into the potential involvement of pyrin containing 3 gene(NLRP3), a member of the nucleotide-binding oligomerization domain-like receptors with cytosolic pattern recognition, in the host defense of...AIM: To investigate into the potential involvement of pyrin containing 3 gene(NLRP3), a member of the nucleotide-binding oligomerization domain-like receptors with cytosolic pattern recognition, in the host defense of corneas against viruses.METHODS: The herpes viral keratitis model was utilized in BALB/c mice with inoculation of herpes simplex virus-1(HSV-1). Corneal tissues removed during therapy of patients with viral keratitis as well as a Simian vacuolating virus 40(SV40)-immortalized human corneal epithelial cell line were also examined.Immunohistochemistry was used to detect NLRP3 in these subjects, focusing on their distribution in tissue or cells. Western blot was used to measure the level of NLRP3 and another two related molecules in NLPR3 inflammasome, namely caspase-1 and IL-1β.RESULTS: The NLRP3 activation induced by HSV-1infection in corneas was accompanied with redistribution of NLRP3 from the cytoplasm to the nucleus in both murine and human corneal epithelial cells. Furthermore,in the SV40-immortalized human corneal epithelial cells,NLRP3 was exclusively located in the nucleus, and treatment of the cells with high concentration of extracellular potassium(known as an inhibitor of NLRP3activation) effectively drove NLRP3 back to the cytoplasm as reflected by both immunohistochemistry and Western blot.· CONCLUSION: It is proposed that herpes virus infection activates and causes redistribution of NLRP3 to nuclei. Whether this NLRP3 translocation occurs with other viral infections and in other cell types merit further study.展开更多
The Wnt/β-catenin signaling pathway is instrumental in successful differentiation and proliferation of mammalian cells. It is therefore not surprising that the herpesvirus family has developed mechanisms to interact ...The Wnt/β-catenin signaling pathway is instrumental in successful differentiation and proliferation of mammalian cells. It is therefore not surprising that the herpesvirus family has developed mechanisms to interact with and manipulate this pathway. Successful coexistence with the host requires that herpesviruses establish a lifelong infection that includes periods of latency and reactivation or persistence. Many herpesviruses establish latency in progenitor cells and viral reactivation is linked to host-cell proliferation and differentiation status. Importantly, Wnt/β-catenin is tightly connected to stem/progenitor cell maintenance and differentiation. Numerous studies have linked Wnt/β-catenin signaling to a variety of cancers, emphasizing the importance of Wnt/β-catenin pathways in development, tissue homeostasis and disease. This review details how the alpha-, beta-, and gammaherpesviruses interact and manipulate the Wnt/β-catenin pathway to promote a virus-centric agenda.展开更多
Herpes simplex virus-1 (HSV-1) remains a leading cause of viral disease worldwide and is spread by direct contact with infected lesions. There is no vaccine against HSV-1 infections and there remains a need to identif...Herpes simplex virus-1 (HSV-1) remains a leading cause of viral disease worldwide and is spread by direct contact with infected lesions. There is no vaccine against HSV-1 infections and there remains a need to identify therapeutics that could reduce the spread. In this study various hispolon compounds were analyzed to determine their antiviral potential against HSV-1 infections in cultured Vero cells. To determine the effects on infectivity and possible mechanisms of inhibition, the following assays were conducted. In vitro cytotoxicity assays were conducted to determine the effect of the compounds on cell viability and the maximum non-cytotoxic concentrations. Antiviral assays measured cell viability, percent inhibition of infection following treatment with the compounds, and the effect on the viral infection cycle. These effects were visualized using inverted light and fluorescent microscopy. Of the 24 hispolons tested, only hispolon pyrazole-1 (HISP-1) demonstrated antiviral effects. HISP-1 was demonstrated to effect early stages in HSV-1 infection in cultured Vero cells (attachment, penetration, and post-penetration). In silico modeling analyses were conducted to analyze the interactions between HISP-1 and viral glycoprotein D (gD). HISP-1 is safe at concentrations tested and is effective in inhibiting infection of HSV-1 in cultured cells. HISP-1 has potential for therapeutic use as an antiviral against HSV-1 infection, could work in synergy with other antivirals that work be a different modality, and could be developed as a component of a topical agent to reduce the spread of HSV-1 infections.展开更多
Herpes simplex virus-1(HSV-1)is a widespread neurotropic virus that can reach the brain and cause a rare but acute herpes simplex encephalitis(HSE)with a high mortality rate.Most patients present with changes in neuro...Herpes simplex virus-1(HSV-1)is a widespread neurotropic virus that can reach the brain and cause a rare but acute herpes simplex encephalitis(HSE)with a high mortality rate.Most patients present with changes in neurological and behavioral status,and survivors suffer long-term neurological sequelae.To date,the pathogenesis leading to brain damage is still not well understood.HSV-1 induced encephalitis in the central nervous system(CNS)in animals are usually very diffuse and progressing rapidly,and mostly fatal,making the analysis difficult.Here,we established a mouse model of HSE via intracerebral inoculation of modified version of neuralattenuated strains of HSV-1(deletion of ICP34.5 and inserting a strong promoter into the latency-associated transcript region),in which the LMR-αΔpA strain initiated moderate productive infection,leading to strong host immune and inflammatory response characterized by persistent microglia activation.This viral replication activity and prolonged inflammatory response activated signaling pathways in neuronal damage,amyloidosis,Alzheimer's disease,and neurodegeneration,eventually leading to neuronal loss and behavioral changes characterized by hypokinesia.Our study reveals detailed pathogenic processes and persistent inflammatory responses in the CNS and provides a controlled,mild and non-lethal HSE model for studying long-term neuronal injury and increased risk of neurodegenerative diseases due to HSV-1 infection.展开更多
Honokiol is a pleiotropic natural compound isolated from Magnolia and has multiple biological and clinically relevant effects,including anticancer and antimicrobial function.However,the antiviral activity of honokiol ...Honokiol is a pleiotropic natural compound isolated from Magnolia and has multiple biological and clinically relevant effects,including anticancer and antimicrobial function.However,the antiviral activity of honokiol has not yet been well studied.Here we showed that honokiol had no effect on herpes simplex virus-1(HSV-1)entry,but inhibited HSV-1 viral DNA replication,gene expression and the production of new progeny viruses.The combination of honokiol and clinical drug acyclovir augmented inhibition of HSV-1 infection.Our results illustrate that honokiol could be a potential new candidate for clinical consideration in the treatment of HSV-1 infection alone or combination with other therapeutics.展开更多
To date, 29 distinct microRNAs(miRNAs) have been reported to be expressed during herpes simplex virus infections.Sequence analysis of mature herpes simplex virus-1(HSV-1) miRNAs revealed five sets of miRNAs that are c...To date, 29 distinct microRNAs(miRNAs) have been reported to be expressed during herpes simplex virus infections.Sequence analysis of mature herpes simplex virus-1(HSV-1) miRNAs revealed five sets of miRNAs that are complementary to each other: miR-H6-5p/H1-3p, miR-H6-3p/H1-5p, H2-5p/H14-3p, miR-H2-3p/H14-5p, and miR-H7/H27.However, the roles of individual miRNAs and consequences of this complementarity remain unclear. Here, we focus on two of these complementary miRNAs, miR-H6-5p and miR-H1-3p, using loss-of-function experiments in vitro and in a mouse model of infection using an miRNA sponge approach, including tandem multiplex artificial miRNA-binding sequences that do not match perfectly to the target miRNA inserted downstream of a green fluorescent protein reporter gene. Infection with recombinant virus expressing the miR-H6-5p sponge reduced viral protein levels and virus yield.Decreased accumulation of viral proteins was also observed at early stages of infection in the presence of both an miR-H6-5p inhibitor and plasmid-expressed miR-H1-3p. Moreover, establishment of latency and reactivation did not differ between the recombinant virus expressing the miR-H6-5p sponge and wild-type HSV-1. Taken together, these data suggest that miR-H6-5p has an as-yet-unidentified role in the early stages of viral infection, and its complement miR-H1-3p suppresses this role in later stages of infection. This report extends understanding of the roles of miRNAs in infection by herpes simplex viruses, supporting a model of infection in which the production of virus and its virulent effects are tightly controlled to maximize persistence in the host and population.展开更多
文摘Allicin, an antioxidant, is known for providing garlic with its unique fragrance and taste, as well as for its antimicrobial properties. Black garlic, a fermented form of garlic, contains higher levels of antioxidants than fresh garlic. Antioxidants play a vital role in alleviating cellular stress during viral infections. Viral infections result in oxidative stress through the production of reactive oxidative species (ROS). A prolonged state of oxidative stress can result in cell death, DNA damage, and disease progression. In this study, black garlic extract (BGE) is evaluated for its ability to mitigate cytopathic effects and oxidative stress caused by herpes simplex virus-2 (HSV-2) infections in vitro. Antiviral assays were performed to determine the percent of viral inhibition resulting from treatment with the BGE. ROS-Glo<sup>TM</sup> H<sub>2</sub>O<sub>2</sub> assays were then completed to measure the post-infection ROS levels of BGE-treated virus and cells. The results thus far suggest that BGE may inhibit viral infection and decrease levels of oxidative stress.
基金Supported by National Natural Science Foundation of China(No.81273212,81100651)Project of Science and Technology of Shandong Province(No.2014GSF118044)
文摘AIM: To investigate into the potential involvement of pyrin containing 3 gene(NLRP3), a member of the nucleotide-binding oligomerization domain-like receptors with cytosolic pattern recognition, in the host defense of corneas against viruses.METHODS: The herpes viral keratitis model was utilized in BALB/c mice with inoculation of herpes simplex virus-1(HSV-1). Corneal tissues removed during therapy of patients with viral keratitis as well as a Simian vacuolating virus 40(SV40)-immortalized human corneal epithelial cell line were also examined.Immunohistochemistry was used to detect NLRP3 in these subjects, focusing on their distribution in tissue or cells. Western blot was used to measure the level of NLRP3 and another two related molecules in NLPR3 inflammasome, namely caspase-1 and IL-1β.RESULTS: The NLRP3 activation induced by HSV-1infection in corneas was accompanied with redistribution of NLRP3 from the cytoplasm to the nucleus in both murine and human corneal epithelial cells. Furthermore,in the SV40-immortalized human corneal epithelial cells,NLRP3 was exclusively located in the nucleus, and treatment of the cells with high concentration of extracellular potassium(known as an inhibitor of NLRP3activation) effectively drove NLRP3 back to the cytoplasm as reflected by both immunohistochemistry and Western blot.· CONCLUSION: It is proposed that herpes virus infection activates and causes redistribution of NLRP3 to nuclei. Whether this NLRP3 translocation occurs with other viral infections and in other cell types merit further study.
文摘The Wnt/β-catenin signaling pathway is instrumental in successful differentiation and proliferation of mammalian cells. It is therefore not surprising that the herpesvirus family has developed mechanisms to interact with and manipulate this pathway. Successful coexistence with the host requires that herpesviruses establish a lifelong infection that includes periods of latency and reactivation or persistence. Many herpesviruses establish latency in progenitor cells and viral reactivation is linked to host-cell proliferation and differentiation status. Importantly, Wnt/β-catenin is tightly connected to stem/progenitor cell maintenance and differentiation. Numerous studies have linked Wnt/β-catenin signaling to a variety of cancers, emphasizing the importance of Wnt/β-catenin pathways in development, tissue homeostasis and disease. This review details how the alpha-, beta-, and gammaherpesviruses interact and manipulate the Wnt/β-catenin pathway to promote a virus-centric agenda.
文摘Herpes simplex virus-1 (HSV-1) remains a leading cause of viral disease worldwide and is spread by direct contact with infected lesions. There is no vaccine against HSV-1 infections and there remains a need to identify therapeutics that could reduce the spread. In this study various hispolon compounds were analyzed to determine their antiviral potential against HSV-1 infections in cultured Vero cells. To determine the effects on infectivity and possible mechanisms of inhibition, the following assays were conducted. In vitro cytotoxicity assays were conducted to determine the effect of the compounds on cell viability and the maximum non-cytotoxic concentrations. Antiviral assays measured cell viability, percent inhibition of infection following treatment with the compounds, and the effect on the viral infection cycle. These effects were visualized using inverted light and fluorescent microscopy. Of the 24 hispolons tested, only hispolon pyrazole-1 (HISP-1) demonstrated antiviral effects. HISP-1 was demonstrated to effect early stages in HSV-1 infection in cultured Vero cells (attachment, penetration, and post-penetration). In silico modeling analyses were conducted to analyze the interactions between HISP-1 and viral glycoprotein D (gD). HISP-1 is safe at concentrations tested and is effective in inhibiting infection of HSV-1 in cultured cells. HISP-1 has potential for therapeutic use as an antiviral against HSV-1 infection, could work in synergy with other antivirals that work be a different modality, and could be developed as a component of a topical agent to reduce the spread of HSV-1 infections.
基金supported by grants from the National Natural Science Foundation of China-Yunnan Joint Found(NSFC,U2202215,U1602226)the National Natural Science Foundation of China(NSFC,81672040 to J.Zhou,8206306 to X.Cao,and 31802026 to L.Li)+11 种基金the Ministry of Science and Technology of China(MOST,2018YFC2000402,2018YFE0203700)the Ministry of Science and Technology of China Foreign Expert Program to J.Zhou(G2021061008L)the CAS“Light of West China”Program(xbzg-zdsys-201909)to J.Zhou,a Thousand Foreign Talent scholarship from Yunnan Province and High-end Foreign Expert Project of Yunnan Revitalization Talent Support Program to J.Zhouthe Technology Innovation Team of Kunming Medical University(CXTD201804)the International Science and Technology Cooperation Project(2017IB011)the Yunnan Training Project for Medical Talents(L-2017014)the biomedical Special Project of the Department of Science and Technology of Yunnan Province(202102AA100007-4)to X.Caothe Chinese Academy of Sciences President's International Fellowship Initiative(PIFI,2019VBA0045)to N.W.Fraserthe China Postdoctoral Science Foundation(2022MD713758)to E.Wangthe Medical reserve Talents Training Program of Yunnan Provincial Health Commission of China(H-2019059)to X.Huangthe Yunnan Fundamental Research Projects(202201AT070195)to Y.Ye.Open Research Fund HXDT-2019-1 to J.Zhou.
文摘Herpes simplex virus-1(HSV-1)is a widespread neurotropic virus that can reach the brain and cause a rare but acute herpes simplex encephalitis(HSE)with a high mortality rate.Most patients present with changes in neurological and behavioral status,and survivors suffer long-term neurological sequelae.To date,the pathogenesis leading to brain damage is still not well understood.HSV-1 induced encephalitis in the central nervous system(CNS)in animals are usually very diffuse and progressing rapidly,and mostly fatal,making the analysis difficult.Here,we established a mouse model of HSE via intracerebral inoculation of modified version of neuralattenuated strains of HSV-1(deletion of ICP34.5 and inserting a strong promoter into the latency-associated transcript region),in which the LMR-αΔpA strain initiated moderate productive infection,leading to strong host immune and inflammatory response characterized by persistent microglia activation.This viral replication activity and prolonged inflammatory response activated signaling pathways in neuronal damage,amyloidosis,Alzheimer's disease,and neurodegeneration,eventually leading to neuronal loss and behavioral changes characterized by hypokinesia.Our study reveals detailed pathogenic processes and persistent inflammatory responses in the CNS and provides a controlled,mild and non-lethal HSE model for studying long-term neuronal injury and increased risk of neurodegenerative diseases due to HSV-1 infection.
基金supported by the grant from National Key Research and Development Program (2016YFA0502100)
文摘Honokiol is a pleiotropic natural compound isolated from Magnolia and has multiple biological and clinically relevant effects,including anticancer and antimicrobial function.However,the antiviral activity of honokiol has not yet been well studied.Here we showed that honokiol had no effect on herpes simplex virus-1(HSV-1)entry,but inhibited HSV-1 viral DNA replication,gene expression and the production of new progeny viruses.The combination of honokiol and clinical drug acyclovir augmented inhibition of HSV-1 infection.Our results illustrate that honokiol could be a potential new candidate for clinical consideration in the treatment of HSV-1 infection alone or combination with other therapeutics.
基金supported by grants from Shenzhen Science and Innovation Commission Project Grants JCYJ20170411094933148Dapeng Research Project Grants KY20160301 to Shenzhen International Institute for Biomedical Research+1 种基金Guangzhou Science and Innovation Commission Project Grants 2016070100039Guangzhou Education Bureau Project Grants 1201620034 to Guangzhou Medical University
文摘To date, 29 distinct microRNAs(miRNAs) have been reported to be expressed during herpes simplex virus infections.Sequence analysis of mature herpes simplex virus-1(HSV-1) miRNAs revealed five sets of miRNAs that are complementary to each other: miR-H6-5p/H1-3p, miR-H6-3p/H1-5p, H2-5p/H14-3p, miR-H2-3p/H14-5p, and miR-H7/H27.However, the roles of individual miRNAs and consequences of this complementarity remain unclear. Here, we focus on two of these complementary miRNAs, miR-H6-5p and miR-H1-3p, using loss-of-function experiments in vitro and in a mouse model of infection using an miRNA sponge approach, including tandem multiplex artificial miRNA-binding sequences that do not match perfectly to the target miRNA inserted downstream of a green fluorescent protein reporter gene. Infection with recombinant virus expressing the miR-H6-5p sponge reduced viral protein levels and virus yield.Decreased accumulation of viral proteins was also observed at early stages of infection in the presence of both an miR-H6-5p inhibitor and plasmid-expressed miR-H1-3p. Moreover, establishment of latency and reactivation did not differ between the recombinant virus expressing the miR-H6-5p sponge and wild-type HSV-1. Taken together, these data suggest that miR-H6-5p has an as-yet-unidentified role in the early stages of viral infection, and its complement miR-H1-3p suppresses this role in later stages of infection. This report extends understanding of the roles of miRNAs in infection by herpes simplex viruses, supporting a model of infection in which the production of virus and its virulent effects are tightly controlled to maximize persistence in the host and population.
