基于非结构蛋白1(NS1)的黄病毒感染诊断研究进展
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摘要
蚊虫传播的黄病毒造成的传染病是人类健康的重要威胁,有效的早期精确诊断对预防与控制黄病毒感染并及时有效开展病患救治至关重要。然而由于黄病毒在血液中核酸可检测窗口短,核酸检测手段难以发挥优势,必须要通过血清学的诊断与病毒分离予以佐证,而血清学检测也要面对黄病毒之间存在的交叉反应问题。本文介绍了基于黄病毒非结构蛋白1(NS1)建立的检测手段。NS1蛋白在病人血清中含量很高是良好早期诊断靶标,基于NS1蛋白的黄病毒血清学诊断的检测窗口较长、灵敏度高、特异性强,具有独特的优势。尤其是2016年寨卡病毒暴发以来基于NS1的检测技术在灵敏度与特异性上得到快速与多元的发展,为黄病毒的精确检测带开启了新的局面。
Mosquito-borne flaviviruses provide some of the most important examples of emerging and resurging diseases of global significance. The early diagnosis of flaviviruses infection is important for successful clinical management and epidemiological control. Multiple RT-PCR-based assays for the detection of flaviviruses are limited to the narrow window when viral RNA is detectable in body fluids. Therefore,host immune reponsebased assays play an important role. Unfortunately,flaviviruses diagnosis are challenging due to the cross-reactive nature of antibodies among flaviviruses. The non-structural protein 1( NS1) of flavivirus,a highly conserved and secreted glycoprotein,is abundant in the serum of flavivirus-infected patients and represents a useful early diagnostic marker. After ZIKV emerged as a global health threat,causing a pandemic in the Americas at 2016,lots of research groups focus on the NS1 based diagnosis. The improvements either from strategy or technology,which would significantly improve the differential diagnosis among flaviviruses infections.
Mosquito-borne flaviviruses provide some of the most important examples of emerging and resurging diseases of global significance. The early diagnosis of flaviviruses infection is important for successful clinical management and epidemiological control. Multiple RT-PCR-based assays for the detection of flaviviruses are limited to the narrow window when viral RNA is detectable in body fluids. Therefore,host immune reponsebased assays play an important role. Unfortunately,flaviviruses diagnosis are challenging due to the cross-reactive nature of antibodies among flaviviruses. The non-structural protein 1( NS1) of flavivirus,a highly conserved and secreted glycoprotein,is abundant in the serum of flavivirus-infected patients and represents a useful early diagnostic marker. After ZIKV emerged as a global health threat,causing a pandemic in the Americas at 2016,lots of research groups focus on the NS1 based diagnosis. The improvements either from strategy or technology,which would significantly improve the differential diagnosis among flaviviruses infections.
引文
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[10] Landry M L,St George K. Laboratory diagnosis of zika virus infection. Archives of Pathology&Laboratory Medicine,2017,141:60-67.
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[12] Stettler K,Beltramello M,Espinosa D A,et al. Specificity,cross-reactivity,and function of antibodies elicited by zika virus infection. Science,2016,353:823-826.
[13]Song H,Qi J,Haywood J,et al. Zika virus ns1 structure reveals diversity of electrostatic surfaces among flaviviruses. Nature structural&Molecular biology,2016,23:456-458.
[14]Heffron A S,Mohr E L,Baker D,et al. Antibody responses to zika virus proteins in pregnant and non-pregnant macaques. PLo S neglected tropical diseases,2018,12:e0006903.
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[22]Akey DL,Brown WC,Dutta S,et al. Flavivirus ns1 structures reveal surfaces for associations with membranes and the immune system. Science,2014,343:881-885.
[23]Edeling M A,Diamond M S,Fremont D H. Structural basis of flavivirus ns1 assembly and antibody recognition. Proceedings of the National Academy of Sciences of the United States of America,2014,111:4285-4290.
[24]Young P R,Hilditch P A,Bletchly C,et al. An antigen capture enzyme-linked immunosorbent assay reveals high levels of the dengue virus protein ns1 in the sera of infected patients. Journal of Clinical Microbiology,2000,38:1053-1057.
[25] Konishi E,Suzuki T. Ratios of subclinical to clinical japanese encephalitis(je)virus infections in vaccinated populations:Evaluation of an inactivated je vaccine by comparing the ratios with those in unvaccinated populations. Vaccine,2002,21:98-107.
[26]Chao D Y,Galula J U,Shen W F,et al. Nonstructural protein 1-specific immunoglobulin m and g antibody capture enzyme-linked immunosorbent assays in diagnosis of flaviviral infections in humans. Journal of Clinical Microbiology,2015,53:557-566.
[27]Balmaseda A,Stettler K,Medialdea-Carrera R,et al. Antibodybased assay discriminates zika virus infection from other flaviviruses. Proceedings of the National Academy of Sciences of the United States of America,2017,114:8384-8389.
[28]Zhang B,Pinsky B A,Ananta J S,et al. Diagnosis of zika virus infection on a nanotechnology platform. Nature Medicine,2017,23:548-550.
[29]Lustig Y,Zelena H,Venturi G,et al. Sensitivity and kinetics of an ns1-based zika virus enzyme-linked immunosorbent assay in zika virus-infected travelers from israel,the czech republic,italy,belgium,germany,and chile. Journal of Clinical Microbiology,2017,55:1894-1901.
[30]Tsai W Y,Youn H H,Brites C,et al. Distinguishing secondary dengue virus infection from zika virus infection with previous dengue by a combination of 3 simple serological tests. Clinical Infectious Diseases,2017,65:1829-1836.
[31]Lustig Y,Mendelson E,Paran N,et al. Detection of zika virus rna in whole blood of imported zika virus disease cases up to 2months after symptom onset,israel,december 2015 to april 2016.Eurosurveillance,2016,21(26):doi:10. 2807/1560-7917. ES.2016. 21. 26. 30269.
[32] Kikuti M, Tauro L B, Moreira P S S, et al. Diagnostic performance of commercial igm and igg enzyme-linked immunoassays(elisas)for diagnosis of zika virus infection.Virology Journal,2018,15:108.
[33] De Ory F,Sánchez-Seco M P,Vázquez A,et al. Comparative evaluation of indirect immunofluorescence and ns-1-based elisa to determine zika virus-specific igm. Viruses,2018,10(7):E379.
[34]Nurtop E,Villarroel P M S,Pastorino B,et al. Combination of elisa screening and seroneutralisation tests to expedite zika virus seroprevalence studies. Virology Journal,2018,15:192.
[35]Liu LT,Dalipanda T,Jagilly R,et al. Comparison of two rapid diagnostic tests during a large dengue virus serotype 3 outbreak in the solomon islands in 2013. Plo S One,2018,13:e0202304.
[36] Rodriguez-Manzano J,Chia P Y,Yeo TW,et al. Improving dengue diagnostics and management through innovative technology. Current infectious Disease Reports,2018,20:25.
[37]Stambaugh A,Parks J W,Stott M A,et al. Optofluidic detection of zika nucleic acid and protein biomarkers using multimode interference multiplexing. Biomedical Optics Express,2018,9:3725-3730.
[38] Bosch I,de Puig H,Hiley M,et al. Rapid antigen tests for dengue virus serotypes and zika virus in patient serum. Science Translational Medicine,2017,9(409):eaan1589.
[39]Tsai W Y,Youn H H,Tyson J,et al. Use of urea wash elisa to distinguish zika and dengue virus infections. Emerging Infectious Diseases,2018,24:1355-1359.
[40] Gao X,Wen Y,Wang J,et al. Delayed and highly specific antibody response to nonstructural protein 1(ns1)revealed during natural human zikv infection by ns1-based capture elisa. BMC Infectious Diseases,2018,18:275.
[41] Dai H,Xu Z Z,Wang M,et al. Development of a doublemonoclonal antibody sandwich elisa:Tool for chicken interferon-γdetection ex vivo. Canadian Journal of Veterinary Research,2016,80:134-140.
[42]Lustig Y,Sofer D,Bucris E D,et al. Surveillance and diagnosis of west nile virus in the face of flavivirus cross-reactivity. Frontiers in Microbiology,2018,9:2421.
[43]Zhang L,Du X,Chen C,et al. Development and characterization of double-antibody sandwich elisa for detection of zika virus infection. Viruses,2018,10(634):1-12.
[44]Lum F-M,Lin C,Susova O Y,et al. A sensitive method for detecting zika virus antigen in patients’whole-blood specimens as an alternative diagnostic approach. The Journal of Infectious Diseases,2017,216:182-190.
[45] Rockstroh A,Barzon L,Kumbukgolla W,et al. Dengue virus igm serotyping by elisa with recombinant mutant envelope proteins. Emerging Infectious Diseases,2019,25:1111-1115.
[2]Fernandez-Garcia M D,Mazzon M,Jacobs M,et al. Pathogenesis of flavivirus infections:Using and abusing the host cell. Cell Host&Microbe,2009,5:318-328.
[3] Reinhold JM, Lazzari CR, Lahondere C. Effects of the environmental temperature on aedes aegypti and aedes albopictus mosquitoes:A review. Insects,2018,9.
[4] Muller D A,Depelsenaire A C,Young P R. Clinical and laboratory diagnosis of dengue virus infection. The Journal of Infectious Diseases,2017,215:S89-s95.
[5] Domingo C,Charrel R N,Schmidt-Chanasit J,et al. Yellow fever in the diagnostics laboratory. Emerging Microbes&Infections,2018,7:129.
[6] Connor B,Bunn W B. The changing epidemiology of japanese encephalitis and new data:The implications for new recommendations for japanese encephalitis vaccine. Tropical Diseases,Travel Medicine and Vaccines,2017,3:14.
[7]Chancey C,Grinev A,Volkova E,et al. The global ecology and epidemiology of west nile virus. BioMed Research International,2015,2015:376230.
[8] Steinhagen K,Probst C,Radzimski C,et al. Serodiagnosis of zika virus(zikv)infections by a novel ns1-based elisa devoid of cross-reactivity with dengue virus antibodies:A multicohort study of assay performance,2015 to 2016. Euro Surveillance,2016,21(50):pii:30426.
[9] Wong S J,Furuya A,Zou J,et al. A multiplex microsphere immunoassay for zika virus diagnosis. EBioMedicine,2017,16:136-140.
[10] Landry M L,St George K. Laboratory diagnosis of zika virus infection. Archives of Pathology&Laboratory Medicine,2017,141:60-67.
[11] Fritzell C,Rousset D,Adde A,et al. Current challenges and implications for dengue, chikungunya and zika seroprevalence studies worldwide:A scoping review. PLo S Neglected Tropical Diseases,2018,12:e0006533.
[12] Stettler K,Beltramello M,Espinosa D A,et al. Specificity,cross-reactivity,and function of antibodies elicited by zika virus infection. Science,2016,353:823-826.
[13]Song H,Qi J,Haywood J,et al. Zika virus ns1 structure reveals diversity of electrostatic surfaces among flaviviruses. Nature structural&Molecular biology,2016,23:456-458.
[14]Heffron A S,Mohr E L,Baker D,et al. Antibody responses to zika virus proteins in pregnant and non-pregnant macaques. PLo S neglected tropical diseases,2018,12:e0006903.
[15] Martinez J D,Garza J A C,Cuellar-Barboza A. Going viral2019:Zika,chikungunya,and dengue. Dermatologic Clinics,2019,37:95-105.
[16] Mandl C W,Guirakhoo F,Holzmann H,et al. Antigenic structure of the flavivirus envelope protein e at the molecular level,using tick-borne encephalitis virus as a model. Journal of Virology,1989,63:564-571.
[17] Rockstroh A,Moges B,Barzon L,et al. Specific detection of dengue and zika virus antibodies using envelope proteins with mutations in the conserved fusion loop. Emerging Microbes&Infections,2017,6:e99.
[18]Rockstroh A,Barzon L,Pacenti M,et al. Recombinant envelopeproteins with mutations in the conserved fusion loop allow specific serological diagnosis of dengue-infections. PLo S Neglected Tropical Diseases,2015,9:e0004218.
[19]Garcia G,Vaughn D W,Del Angel R M. Recognition of synthetic oligopeptides from nonstructural proteins ns1 and ns3 of dengue-4virus by sera from dengue virus-infected children. The American Journal of Tropical Medicine And Hygiene,1997,56:466-470.
[20]Shu P Y,Chen L K,Chang S F,et al. Potential application of nonstructural protein ns1 serotype-specific immunoglobulin g enzyme-linked immunosorbent assay in the seroepidemiologic study of dengue virus infection:Correlation of results with those of the plaque reduction neutralization test. Journal of Clinical Microbiology,2002,40:1840-1844.
[21] Wong S J,Boyle R H,Demarest V L,et al. Immunoassay targeting nonstructural protein 5 to differentiate west nile virus infection from dengue and st. Louis encephalitis virus infections and from flavivirus vaccination. Journal of Clinical Microbiology,2003,41:4217-4223.
[22]Akey DL,Brown WC,Dutta S,et al. Flavivirus ns1 structures reveal surfaces for associations with membranes and the immune system. Science,2014,343:881-885.
[23]Edeling M A,Diamond M S,Fremont D H. Structural basis of flavivirus ns1 assembly and antibody recognition. Proceedings of the National Academy of Sciences of the United States of America,2014,111:4285-4290.
[24]Young P R,Hilditch P A,Bletchly C,et al. An antigen capture enzyme-linked immunosorbent assay reveals high levels of the dengue virus protein ns1 in the sera of infected patients. Journal of Clinical Microbiology,2000,38:1053-1057.
[25] Konishi E,Suzuki T. Ratios of subclinical to clinical japanese encephalitis(je)virus infections in vaccinated populations:Evaluation of an inactivated je vaccine by comparing the ratios with those in unvaccinated populations. Vaccine,2002,21:98-107.
[26]Chao D Y,Galula J U,Shen W F,et al. Nonstructural protein 1-specific immunoglobulin m and g antibody capture enzyme-linked immunosorbent assays in diagnosis of flaviviral infections in humans. Journal of Clinical Microbiology,2015,53:557-566.
[27]Balmaseda A,Stettler K,Medialdea-Carrera R,et al. Antibodybased assay discriminates zika virus infection from other flaviviruses. Proceedings of the National Academy of Sciences of the United States of America,2017,114:8384-8389.
[28]Zhang B,Pinsky B A,Ananta J S,et al. Diagnosis of zika virus infection on a nanotechnology platform. Nature Medicine,2017,23:548-550.
[29]Lustig Y,Zelena H,Venturi G,et al. Sensitivity and kinetics of an ns1-based zika virus enzyme-linked immunosorbent assay in zika virus-infected travelers from israel,the czech republic,italy,belgium,germany,and chile. Journal of Clinical Microbiology,2017,55:1894-1901.
[30]Tsai W Y,Youn H H,Brites C,et al. Distinguishing secondary dengue virus infection from zika virus infection with previous dengue by a combination of 3 simple serological tests. Clinical Infectious Diseases,2017,65:1829-1836.
[31]Lustig Y,Mendelson E,Paran N,et al. Detection of zika virus rna in whole blood of imported zika virus disease cases up to 2months after symptom onset,israel,december 2015 to april 2016.Eurosurveillance,2016,21(26):doi:10. 2807/1560-7917. ES.2016. 21. 26. 30269.
[32] Kikuti M, Tauro L B, Moreira P S S, et al. Diagnostic performance of commercial igm and igg enzyme-linked immunoassays(elisas)for diagnosis of zika virus infection.Virology Journal,2018,15:108.
[33] De Ory F,Sánchez-Seco M P,Vázquez A,et al. Comparative evaluation of indirect immunofluorescence and ns-1-based elisa to determine zika virus-specific igm. Viruses,2018,10(7):E379.
[34]Nurtop E,Villarroel P M S,Pastorino B,et al. Combination of elisa screening and seroneutralisation tests to expedite zika virus seroprevalence studies. Virology Journal,2018,15:192.
[35]Liu LT,Dalipanda T,Jagilly R,et al. Comparison of two rapid diagnostic tests during a large dengue virus serotype 3 outbreak in the solomon islands in 2013. Plo S One,2018,13:e0202304.
[36] Rodriguez-Manzano J,Chia P Y,Yeo TW,et al. Improving dengue diagnostics and management through innovative technology. Current infectious Disease Reports,2018,20:25.
[37]Stambaugh A,Parks J W,Stott M A,et al. Optofluidic detection of zika nucleic acid and protein biomarkers using multimode interference multiplexing. Biomedical Optics Express,2018,9:3725-3730.
[38] Bosch I,de Puig H,Hiley M,et al. Rapid antigen tests for dengue virus serotypes and zika virus in patient serum. Science Translational Medicine,2017,9(409):eaan1589.
[39]Tsai W Y,Youn H H,Tyson J,et al. Use of urea wash elisa to distinguish zika and dengue virus infections. Emerging Infectious Diseases,2018,24:1355-1359.
[40] Gao X,Wen Y,Wang J,et al. Delayed and highly specific antibody response to nonstructural protein 1(ns1)revealed during natural human zikv infection by ns1-based capture elisa. BMC Infectious Diseases,2018,18:275.
[41] Dai H,Xu Z Z,Wang M,et al. Development of a doublemonoclonal antibody sandwich elisa:Tool for chicken interferon-γdetection ex vivo. Canadian Journal of Veterinary Research,2016,80:134-140.
[42]Lustig Y,Sofer D,Bucris E D,et al. Surveillance and diagnosis of west nile virus in the face of flavivirus cross-reactivity. Frontiers in Microbiology,2018,9:2421.
[43]Zhang L,Du X,Chen C,et al. Development and characterization of double-antibody sandwich elisa for detection of zika virus infection. Viruses,2018,10(634):1-12.
[44]Lum F-M,Lin C,Susova O Y,et al. A sensitive method for detecting zika virus antigen in patients’whole-blood specimens as an alternative diagnostic approach. The Journal of Infectious Diseases,2017,216:182-190.
[45] Rockstroh A,Barzon L,Kumbukgolla W,et al. Dengue virus igm serotyping by elisa with recombinant mutant envelope proteins. Emerging Infectious Diseases,2019,25:1111-1115.