A 62-year-old man had chronic hepatitis B virus （HBV） infection and was diagnosed with liver cirrhosis. At the time of diagnosis the patient＇s virologic markers were positive for hepatitis B surface antigen （HBsAg...A 62-year-old man had chronic hepatitis B virus （HBV） infection and was diagnosed with liver cirrhosis. At the time of diagnosis the patient＇s virologic markers were positive for hepatitis B surface antigen （HBsAg）, antibody to hepatitis B e antigen （anti-HBe） and antibody to hepatitis B core antigen （anti-HBc）, while antibody to hepatitis B surface antigen （anti-HBs） and HBV DNA were negative. Later the patient received chemotherapy for malignancy. However, this was interrupted due to elevated liver enzymes. At the same time HBV DNA became positive. Lamivudine （LMV） therapy was administered immediately. However, the levels of serum aminotransferase and total bilirubin （TB） were still rising. Finally the patient died of fulminant hepatic failure. A sequence revealed HBV genotype C （HBsAg subtype adw） with immune escape mutations, F8L, $34L, F41S, G44V, F93C, V96G, Lll0I, C149Y and F161Y. The high morbidity and mortality of this complication is one of the major obstacles to completing the standard treatment for malignancy in HBV carriers. Therefore, the relative risk of antiviral prophylactic failure should be further assessed and the optimal strategy for antiviral prophylaxis in HBsAg-positive patients with oncologic and hematologic malignancies undergoing chemotherapy should be revised.展开更多
Dear Editor,We report a case of HBV reactivation in an anti-HBs positive, anti-HBc positive non-Hodgkin’s lymphoma patient. Hepatitis B virus (HBV) reactivation is a well-recognized complication of patients undergoin...Dear Editor,We report a case of HBV reactivation in an anti-HBs positive, anti-HBc positive non-Hodgkin’s lymphoma patient. Hepatitis B virus (HBV) reactivation is a well-recognized complication of patients undergoing chemotherapy or immunosuppressive therapy for lymphomas. The presence of antibodies to the展开更多
Feasible and effective cell models for hepatitis B virus(HBV) infection are required for investigating the complete lifecycle of this virus, including the early steps of viral entry. Resistance to dimethyl sulfoxide/p...Feasible and effective cell models for hepatitis B virus(HBV) infection are required for investigating the complete lifecycle of this virus, including the early steps of viral entry. Resistance to dimethyl sulfoxide/polyethylene glycol(DMSO/PEG), h NTCP expression, and a differentiated state are the limiting factors for successful HBV infection models. In the present study, we used a hepatoma cell line(Hu7^(hDNTCPh)) to overcome these limiting factors so that it exhibits excellent susceptibility to HBV infection. To achieve this goal, different hepatoma cell lines were tested with 2.5% DMSO/4%PEG8000, and one resistant cell line(Huh7 D) was used to construct a stable h NTCP-expressing cell line(Hu7^(hDNTCPh)) using a recombinant lentivirus system. Then, the morphological characteristics and differentiation molecular markers of Hu7^(hDNTCPh) cells with or without DMSO treatment were characterized. Finally, the susceptibility of Hu7^(hDNTCPh) cells to HBV infection was assessed. Our results showed that Huh7 D cells were resistant to 2.5% DMSO/4% PEG8000, whereas the others were not. Hu7^(hDNTCPh) cells were established to express a high level of h NTCP compared to liver extracts, and Hu7^(hDNTCPh) cells rapidly transformed into a non-dividing, well-differentiated polarized phenotype under DMSO treatment. Hu7^(hDNTCPh) cells fully supported the entire lifecycle of HBV infection. This cell culture system will be useful for the analysis of host-virus interactions, which should facilitate the discovery of antiviral drugs and vaccines.展开更多
As the open reading frames of hepatitis B virus(HBV)genomes are overlapping,resistance mutations(MTs)in HBV polymerase may result in stop codon MTs in hepatitis B surface proteins,which are usually detected as a mixed...As the open reading frames of hepatitis B virus(HBV)genomes are overlapping,resistance mutations(MTs)in HBV polymerase may result in stop codon MTs in hepatitis B surface proteins,which are usually detected as a mixed population with wild-type(WT)HBV.The question was raised how the coexistence of nucleos(t)ide analogs(NAs)resistance MTs and WT sequences affects HBV replication.In the present study,HBV genomes with frequently detected reverse transcriptase(RT)/surface truncation MTs,rtA181T/sW172^*,rtV191I/sW182^*and rtM204I/sW196^*,were phenotypically characterized alone or together with their WT counterparts in different ratios by transient transfection in the absence or presence of Nas.In the absence of Nas,RT/surface truncation MTs impaired the expression and secretion of HBV surface proteins,and had a dose-dependent negative effect on WT HBV virion secretion.However,in the presence of Nas,coexistence of MTs with WT maintained viral replication,and the presence of WT was able to rescue the production of MT HBV virions.Our findings reveal that complementation of WT and MT HBV genomes is highly effective under drug treatment.展开更多
Dear Editor,With an estimated 240 million chronically infected people worldwide,hepatitis B virus(HBV)infection is a major public health problem(Schweitzer et al.,2015).Despite more than 30 years of in tense research,...Dear Editor,With an estimated 240 million chronically infected people worldwide,hepatitis B virus(HBV)infection is a major public health problem(Schweitzer et al.,2015).Despite more than 30 years of in tense research,many aspects of the HBV life cycle still remain unknown.展开更多
Class II HDACs, such as HDAC4, are critical regulators of the immune response in various immune cells;however, its role in innate immunity remains largely unknown.Here, we report that the overexpression of HDAC4 suppr...Class II HDACs, such as HDAC4, are critical regulators of the immune response in various immune cells;however, its role in innate immunity remains largely unknown.Here, we report that the overexpression of HDAC4 suppresses the production of type I interferons triggered by pattern-recognition receptors (PRRs). HDAC4 repressed the translocation of transcription factor IRF3 to the nucleus, thereby decreasing IRF3-mediated IFN-β expression. In particular, we also determined that HDAC4 can be phosphorylated and simultaneously block the phosphorylation of IRF3 at Ser386 and Ser396 by TBK1 and IKKε, respectively, by interacting with the kinase domain of TBK1 and IKKε. Furthermore, IFN-β may stimulate the expression of HDAC4. Our findings suggest that HDAC4 acts as a regulator of PRR signaling and is a novel mechanism of negative feedback regulation for preventing an overreactive innate immune response.展开更多
The phosphatidylserine-specific phospholipase A1(PLA1A)is an essential host factor in hepatitis C virus(HCV)assembly.In this study,we mapped the E2,NS2 and NS5A involved in PLA1A interaction to their lumenal domains a...The phosphatidylserine-specific phospholipase A1(PLA1A)is an essential host factor in hepatitis C virus(HCV)assembly.In this study,we mapped the E2,NS2 and NS5A involved in PLA1A interaction to their lumenal domains and membranous parts,through which they form oligomeric protein complexes to participate in HCV assembly.Multiple regions of PLA1A were involved in their interaction and complex formation.Furthermore,the results represented structures with PLA1A and E2 in closer proximity than NS2 and NS5A,and strongly suggest PLA1 A-E2,s physical interaction in cells.Meanwhile,we mapped the NS5A sequence which participated in PLA1A interaction with the C-terminus of domain 1.Interestingly,these amino acids in the sequence are also essential for viral RNA replication.Further experiments revealed that these four proteins interact with each other.Moreover,PLA1A expression levels were elevated in livers from HCV-infected patients.In conclusion,we exposed the structural determinants of PLA1A,E2,NS2 and NS5A proteins which were important for HCV assembly and provided a detailed characterization of PLA1A in HCV assembly.展开更多
Hepatitis B virus(HBV)/Hepatitis C virus(HCV)coinfection is frequently observed because of the common infection routine.Despite the reciprocal inhibition exerted by HBV and HCV genomes,the coinfection of HBV and HCV i...Hepatitis B virus(HBV)/Hepatitis C virus(HCV)coinfection is frequently observed because of the common infection routine.Despite the reciprocal inhibition exerted by HBV and HCV genomes,the coinfection of HBV and HCV is associated with more severe forms of liver diseases.However,the complexity of viral interference and underlying pathological mechanism is still unclarified.With the demonstration of absence of direct viral interplay,some in vitro studies suggest the indirect effects of viral-host interaction on viral dominance outcome.Here,we comprehensively investigated the viral replication and host immune responses which might mediate the interference between viruses in HBV/HCV coinfected Huh7-NTCP cells and immunocompetent HCV human receptors transgenic ICR mice.We found that presence of HCV significantly inhibited HBV replication in vitro and in vivo irrespective of the coinfection order,while HBV did not affect HCV replication.Pathological alteration was coincidently reproduced in coinfected mice.In addition to the participation of innate immune response,an involvement of HCV in up-regulating HBV-specific immune responses was described to facilitate HBV clearance.Our systems partially recapitulate HBV/HCV coinfection and unveil the uncharacterized adaptive anti-viral immune responses during coinfection,which renews the knowledge on the nature of indirect viral interaction during HBV/HCV coinfection.展开更多
Autophagy,a conserved“self-eating”process for cellular homeostasis,plays a crucial role in the hepatitis B virus(HBV)life cycle,including viral assembly,envelopment,release,and degradation.1 Autophagy can also be hi...Autophagy,a conserved“self-eating”process for cellular homeostasis,plays a crucial role in the hepatitis B virus(HBV)life cycle,including viral assembly,envelopment,release,and degradation.1 Autophagy can also be hijacked by HBV for its persistence and survival.However,the association between HBV mutations and autophagy remains unclear.Herein,we found that an HBV surface antigen(HBsAg)mutation involving sL13H substitution impaired HBsAg expression and caused its abnormal distribution in vitro and in a hydrodynamic injection(HI)-based mouse model for acute HBV infection.The sL13H mutation also decreased autophagosome formation and inhibited autophagic flux.Further mechanistic analysis revealed that sL13H suppresses HBV-induced autophagy initiation by inhibiting the eukaryotic translation initiation factor 2 alpha kinase 3(EIF2AK3/PERK)eeukaryotic translation initiation factor 2 subunit alpha(EIF2S1/eIF2a)eautophagy related(ATG)5/12 axis.Therefore,our findings reveal a potential role for HBV mutations in manipulating host autophagic flux for virus persistence and pathogenesis in chronic hepatitis B.展开更多
Over 40% of the coronavirus disease 2019(COVID-19)COVID-19 patients were asymptomatically infected with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)and the immune responses of these asymptomatic individ...Over 40% of the coronavirus disease 2019(COVID-19)COVID-19 patients were asymptomatically infected with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)and the immune responses of these asymptomatic individuals is a critical factor for developing the strategy to contain the COVID-19 pandemic.Here,we determined the viral dynamics and antibody responses among 143 asymptomatic individuals identified in a massive screening of more than 5 million people in eight districts of Wuhan in May 2020.Asymptomatic individuals were admitted to the government-designated centralized sites in accordance with policy.The incidence rate of asymptomatic infection is〜2.92/100,000.These individuals had low viral copy numbers(peaked at 315 copies/mL)and short-lived antibody responses with the estimated diminish time of 69 days.The antibody responses in individuals with persistent SARS-CoV-2 infection is much longer with the estimated diminish time of 257 days.These results imply that the immune responses in the asymptomatic individuals are not potent enough for preventing SARS-CoV-2 re-infection,which has recently been reported in recovered COVID-19 patients.This casts doubt on the efficacy of forming"herd-immunity"through natural SARS-CoV-2 infection and urges for the development of safe and effective vaccines.展开更多
The severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) epidemic has become a major challenge to public health in China and other countries, considering its pathogenicity across all age groups. Pregnancy is a ...The severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) epidemic has become a major challenge to public health in China and other countries, considering its pathogenicity across all age groups. Pregnancy is a unique physiological condition, and is characterized by altered immunity and elevated hormone levels to actively tolerate the semiallogeneic fetus, which undergoes a sudden and substantial fluctuation during the immediate postpartum period. Changes in clinical features, laboratory characteristics, and imaging features of pregnant women during the pre-partum and postpartum periods require further elucidation. Here, we retrospectively analyzed the clinical features, laboratory characteristics, and imaging features of eight pregnant cases of SARS-CoV-2 infection during the pre-partum and post-partum periods. Our results showed that four of the eight pregnant women were asymptomatic before delivery but became symptomatic post-partum. Correspondingly, white blood cell(WBC) counts increased and lymphocyte(LYMPH) counts decreased. C-reactive protein(CRP) levels in the serum also increased to a higher level than those in general pregnancy.Therefore, it is imperative to closely monitor laboratory parameters including the WBC count, LYMPH count, and CRP,along with other imaging features in chest CT scans, to promptly prevent, diagnose, and treat a SARS-CoV-2 infection during pregnancy.展开更多
Hepatitis B virus(HBV) belongs to Hepadnaviridae family and mainly infects hepatocytes, which can cause acute or chronic hepatitis. Currently, two types of antiviral drugs are approved for chronic infection clinically...Hepatitis B virus(HBV) belongs to Hepadnaviridae family and mainly infects hepatocytes, which can cause acute or chronic hepatitis. Currently, two types of antiviral drugs are approved for chronic infection clinically: interferons and nucleos(t)ide analogues. However, the clinical cure for chronic infection is still rare, and it is a huge challenge for all researchers to develop high-efficiency, safe, non-tolerant, and low-toxicity anti-HBV drugs. Antazoline hydrochloride is a first-generation antihistamine with anticholinergic properties, and it is commonly used to relieve nasal congestion and in eye drops. Recently, an in vitro high-throughput evaluation system was constructed to screen nearly 800 compounds from the Food and Drug Administration(FDA)-approved Drug Library. We found that arbidol hydrochloride and antazoline hydrochloride can effectively reduce HBV DNA in the extracellular supernatant in a dose-dependent manner, with EC_(50) of4.321 lmol/L and 2.910 lmol/L in HepAD38 cells, respectively. Moreover, the antiviral effects and potential mechanism of action of antazoline hydrochloride were studied in different HBV replication systems. The results indicate that antazoline hydrochloride also has a significant inhibitory effect on HBV DNA in the extracellular supernatant of Huh7 cells,with an EC_(50) of 2.349 lmol/L. These findings provide new ideas for screening and research related to HBV agents.展开更多
基金National Basic Research Priorities Program of China(2011CB106303)The National Natural Science Foundation of China(31200699)The Fundamental Research Funds for the Central Universities(HUST:2012QN140)
文摘A 62-year-old man had chronic hepatitis B virus （HBV） infection and was diagnosed with liver cirrhosis. At the time of diagnosis the patient＇s virologic markers were positive for hepatitis B surface antigen （HBsAg）, antibody to hepatitis B e antigen （anti-HBe） and antibody to hepatitis B core antigen （anti-HBc）, while antibody to hepatitis B surface antigen （anti-HBs） and HBV DNA were negative. Later the patient received chemotherapy for malignancy. However, this was interrupted due to elevated liver enzymes. At the same time HBV DNA became positive. Lamivudine （LMV） therapy was administered immediately. However, the levels of serum aminotransferase and total bilirubin （TB） were still rising. Finally the patient died of fulminant hepatic failure. A sequence revealed HBV genotype C （HBsAg subtype adw） with immune escape mutations, F8L, $34L, F41S, G44V, F93C, V96G, Lll0I, C149Y and F161Y. The high morbidity and mortality of this complication is one of the major obstacles to completing the standard treatment for malignancy in HBV carriers. Therefore, the relative risk of antiviral prophylactic failure should be further assessed and the optimal strategy for antiviral prophylaxis in HBsAg-positive patients with oncologic and hematologic malignancies undergoing chemotherapy should be revised.
基金supported by the National Basic Research Priorities Program of China (2011CB106303)National Natural Science Foundation of China(31200699)the Fundamental Research Funds for the Central Universities (HUST: 2012QN140)
文摘Dear Editor,We report a case of HBV reactivation in an anti-HBs positive, anti-HBc positive non-Hodgkin’s lymphoma patient. Hepatitis B virus (HBV) reactivation is a well-recognized complication of patients undergoing chemotherapy or immunosuppressive therapy for lymphomas. The presence of antibodies to the
基金supported by the National Natural Science Foundation of China (Grant number: 81601760, 31621061 and 81461130019)General Financial Grant from the China Postdoctoral Science Foundation (Grant number: 2016M602587)+1 种基金the Shenzhen Foundation of Science and Technology (Grant number: JCYJ20160425 104534335)supported by the Youth Innovation Promotion Association CAS (No.201603)
文摘Feasible and effective cell models for hepatitis B virus(HBV) infection are required for investigating the complete lifecycle of this virus, including the early steps of viral entry. Resistance to dimethyl sulfoxide/polyethylene glycol(DMSO/PEG), h NTCP expression, and a differentiated state are the limiting factors for successful HBV infection models. In the present study, we used a hepatoma cell line(Hu7^(hDNTCPh)) to overcome these limiting factors so that it exhibits excellent susceptibility to HBV infection. To achieve this goal, different hepatoma cell lines were tested with 2.5% DMSO/4%PEG8000, and one resistant cell line(Huh7 D) was used to construct a stable h NTCP-expressing cell line(Hu7^(hDNTCPh)) using a recombinant lentivirus system. Then, the morphological characteristics and differentiation molecular markers of Hu7^(hDNTCPh) cells with or without DMSO treatment were characterized. Finally, the susceptibility of Hu7^(hDNTCPh) cells to HBV infection was assessed. Our results showed that Huh7 D cells were resistant to 2.5% DMSO/4% PEG8000, whereas the others were not. Hu7^(hDNTCPh) cells were established to express a high level of h NTCP compared to liver extracts, and Hu7^(hDNTCPh) cells rapidly transformed into a non-dividing, well-differentiated polarized phenotype under DMSO treatment. Hu7^(hDNTCPh) cells fully supported the entire lifecycle of HBV infection. This cell culture system will be useful for the analysis of host-virus interactions, which should facilitate the discovery of antiviral drugs and vaccines.
基金supported by the Deutsche Forschungsgemeinschaft (TRR60)the National Nature Science Foundation of China (31770180, 31621061)+1 种基金the Youth Innovation Promotion Association CAS (No. 2016303)the Youth Planning Project of Hubei Health Planning Commission (WJ2017Q027)
文摘As the open reading frames of hepatitis B virus(HBV)genomes are overlapping,resistance mutations(MTs)in HBV polymerase may result in stop codon MTs in hepatitis B surface proteins,which are usually detected as a mixed population with wild-type(WT)HBV.The question was raised how the coexistence of nucleos(t)ide analogs(NAs)resistance MTs and WT sequences affects HBV replication.In the present study,HBV genomes with frequently detected reverse transcriptase(RT)/surface truncation MTs,rtA181T/sW172^*,rtV191I/sW182^*and rtM204I/sW196^*,were phenotypically characterized alone or together with their WT counterparts in different ratios by transient transfection in the absence or presence of Nas.In the absence of Nas,RT/surface truncation MTs impaired the expression and secretion of HBV surface proteins,and had a dose-dependent negative effect on WT HBV virion secretion.However,in the presence of Nas,coexistence of MTs with WT maintained viral replication,and the presence of WT was able to rescue the production of MT HBV virions.Our findings reveal that complementation of WT and MT HBV genomes is highly effective under drug treatment.
文摘Dear Editor,With an estimated 240 million chronically infected people worldwide,hepatitis B virus(HBV)infection is a major public health problem(Schweitzer et al.,2015).Despite more than 30 years of in tense research,many aspects of the HBV life cycle still remain unknown.
文摘Class II HDACs, such as HDAC4, are critical regulators of the immune response in various immune cells;however, its role in innate immunity remains largely unknown.Here, we report that the overexpression of HDAC4 suppresses the production of type I interferons triggered by pattern-recognition receptors (PRRs). HDAC4 repressed the translocation of transcription factor IRF3 to the nucleus, thereby decreasing IRF3-mediated IFN-β expression. In particular, we also determined that HDAC4 can be phosphorylated and simultaneously block the phosphorylation of IRF3 at Ser386 and Ser396 by TBK1 and IKKε, respectively, by interacting with the kinase domain of TBK1 and IKKε. Furthermore, IFN-β may stimulate the expression of HDAC4. Our findings suggest that HDAC4 acts as a regulator of PRR signaling and is a novel mechanism of negative feedback regulation for preventing an overreactive innate immune response.
基金supported by grants of the National Basic Research Priorities Program of China (2015CB554304)
文摘The phosphatidylserine-specific phospholipase A1(PLA1A)is an essential host factor in hepatitis C virus(HCV)assembly.In this study,we mapped the E2,NS2 and NS5A involved in PLA1A interaction to their lumenal domains and membranous parts,through which they form oligomeric protein complexes to participate in HCV assembly.Multiple regions of PLA1A were involved in their interaction and complex formation.Furthermore,the results represented structures with PLA1A and E2 in closer proximity than NS2 and NS5A,and strongly suggest PLA1 A-E2,s physical interaction in cells.Meanwhile,we mapped the NS5A sequence which participated in PLA1A interaction with the C-terminus of domain 1.Interestingly,these amino acids in the sequence are also essential for viral RNA replication.Further experiments revealed that these four proteins interact with each other.Moreover,PLA1A expression levels were elevated in livers from HCV-infected patients.In conclusion,we exposed the structural determinants of PLA1A,E2,NS2 and NS5A proteins which were important for HCV assembly and provided a detailed characterization of PLA1A in HCV assembly.
基金supported by National Key Research and Development Program of China(2018YFA0507201 to X.C)the grants from the National Natural Science Foundation of China(81672021 to R.P,31770180 to C.W)。
文摘Hepatitis B virus(HBV)/Hepatitis C virus(HCV)coinfection is frequently observed because of the common infection routine.Despite the reciprocal inhibition exerted by HBV and HCV genomes,the coinfection of HBV and HCV is associated with more severe forms of liver diseases.However,the complexity of viral interference and underlying pathological mechanism is still unclarified.With the demonstration of absence of direct viral interplay,some in vitro studies suggest the indirect effects of viral-host interaction on viral dominance outcome.Here,we comprehensively investigated the viral replication and host immune responses which might mediate the interference between viruses in HBV/HCV coinfected Huh7-NTCP cells and immunocompetent HCV human receptors transgenic ICR mice.We found that presence of HCV significantly inhibited HBV replication in vitro and in vivo irrespective of the coinfection order,while HBV did not affect HCV replication.Pathological alteration was coincidently reproduced in coinfected mice.In addition to the participation of innate immune response,an involvement of HCV in up-regulating HBV-specific immune responses was described to facilitate HBV clearance.Our systems partially recapitulate HBV/HCV coinfection and unveil the uncharacterized adaptive anti-viral immune responses during coinfection,which renews the knowledge on the nature of indirect viral interaction during HBV/HCV coinfection.
基金This work was supported by grants from the National Natural Science Foundation of China(No.82002131,31770180)the Natural Science Foundation Project of CQ CSTC(No.cstc2020jcyj-msxmX0081)Open project of State Key Laboratory of Virology(No.2020IOV006)。
文摘Autophagy,a conserved“self-eating”process for cellular homeostasis,plays a crucial role in the hepatitis B virus(HBV)life cycle,including viral assembly,envelopment,release,and degradation.1 Autophagy can also be hijacked by HBV for its persistence and survival.However,the association between HBV mutations and autophagy remains unclear.Herein,we found that an HBV surface antigen(HBsAg)mutation involving sL13H substitution impaired HBsAg expression and caused its abnormal distribution in vitro and in a hydrodynamic injection(HI)-based mouse model for acute HBV infection.The sL13H mutation also decreased autophagosome formation and inhibited autophagic flux.Further mechanistic analysis revealed that sL13H suppresses HBV-induced autophagy initiation by inhibiting the eukaryotic translation initiation factor 2 alpha kinase 3(EIF2AK3/PERK)eeukaryotic translation initiation factor 2 subunit alpha(EIF2S1/eIF2a)eautophagy related(ATG)5/12 axis.Therefore,our findings reveal a potential role for HBV mutations in manipulating host autophagic flux for virus persistence and pathogenesis in chronic hepatitis B.
基金supported by the National Science and Technology Major Project(No.2018ZX10101004001005)the National Key R&D Program of China(2018YFA0507201)+3 种基金the National Natural Science Foundation of China(No.31770188,32070179 and 31900144)Fundamental Research Funds for Central Public Welfare Scientific Research Institutes sponsored by National Institute of Metrology,P.R.China(grant no.31-ZYZJ2001 and grant no.AKYYJ2009)the Advanced Customer Cultivation Project of Wuhan National Biosafety Laboratory Chinese Academy of Sciences(No.2018ACCP-MS01)the Key Technology Development Program of Shenzhen(grant no.JSGG20200225153042494).
文摘Over 40% of the coronavirus disease 2019(COVID-19)COVID-19 patients were asymptomatically infected with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)and the immune responses of these asymptomatic individuals is a critical factor for developing the strategy to contain the COVID-19 pandemic.Here,we determined the viral dynamics and antibody responses among 143 asymptomatic individuals identified in a massive screening of more than 5 million people in eight districts of Wuhan in May 2020.Asymptomatic individuals were admitted to the government-designated centralized sites in accordance with policy.The incidence rate of asymptomatic infection is〜2.92/100,000.These individuals had low viral copy numbers(peaked at 315 copies/mL)and short-lived antibody responses with the estimated diminish time of 69 days.The antibody responses in individuals with persistent SARS-CoV-2 infection is much longer with the estimated diminish time of 257 days.These results imply that the immune responses in the asymptomatic individuals are not potent enough for preventing SARS-CoV-2 re-infection,which has recently been reported in recovered COVID-19 patients.This casts doubt on the efficacy of forming"herd-immunity"through natural SARS-CoV-2 infection and urges for the development of safe and effective vaccines.
文摘The severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) epidemic has become a major challenge to public health in China and other countries, considering its pathogenicity across all age groups. Pregnancy is a unique physiological condition, and is characterized by altered immunity and elevated hormone levels to actively tolerate the semiallogeneic fetus, which undergoes a sudden and substantial fluctuation during the immediate postpartum period. Changes in clinical features, laboratory characteristics, and imaging features of pregnant women during the pre-partum and postpartum periods require further elucidation. Here, we retrospectively analyzed the clinical features, laboratory characteristics, and imaging features of eight pregnant cases of SARS-CoV-2 infection during the pre-partum and post-partum periods. Our results showed that four of the eight pregnant women were asymptomatic before delivery but became symptomatic post-partum. Correspondingly, white blood cell(WBC) counts increased and lymphocyte(LYMPH) counts decreased. C-reactive protein(CRP) levels in the serum also increased to a higher level than those in general pregnancy.Therefore, it is imperative to closely monitor laboratory parameters including the WBC count, LYMPH count, and CRP,along with other imaging features in chest CT scans, to promptly prevent, diagnose, and treat a SARS-CoV-2 infection during pregnancy.
基金supported by grants from the National Nature Science Foundation of China (31770180)。
文摘Hepatitis B virus(HBV) belongs to Hepadnaviridae family and mainly infects hepatocytes, which can cause acute or chronic hepatitis. Currently, two types of antiviral drugs are approved for chronic infection clinically: interferons and nucleos(t)ide analogues. However, the clinical cure for chronic infection is still rare, and it is a huge challenge for all researchers to develop high-efficiency, safe, non-tolerant, and low-toxicity anti-HBV drugs. Antazoline hydrochloride is a first-generation antihistamine with anticholinergic properties, and it is commonly used to relieve nasal congestion and in eye drops. Recently, an in vitro high-throughput evaluation system was constructed to screen nearly 800 compounds from the Food and Drug Administration(FDA)-approved Drug Library. We found that arbidol hydrochloride and antazoline hydrochloride can effectively reduce HBV DNA in the extracellular supernatant in a dose-dependent manner, with EC_(50) of4.321 lmol/L and 2.910 lmol/L in HepAD38 cells, respectively. Moreover, the antiviral effects and potential mechanism of action of antazoline hydrochloride were studied in different HBV replication systems. The results indicate that antazoline hydrochloride also has a significant inhibitory effect on HBV DNA in the extracellular supernatant of Huh7 cells,with an EC_(50) of 2.349 lmol/L. These findings provide new ideas for screening and research related to HBV agents.
