scholarly journals Computational modelling predicts that Dengue virus antibodies can bind to SARS-CoV-2 receptor binding sites: Is pre-exposure to dengue virus protective against COVID-19 severity?

2020 ◽  
Author(s):  
Himadri Nath ◽  
Abinash Mallick ◽  
Subrata Roy ◽  
Soumi Sukla ◽  
Subhajit Biswas
Keyword(s):  
Dengue Virus ◽  
Receptor Binding ◽  
Computational Modelling ◽  
Docking Studies ◽  
Virus Antigen ◽  
Cross Reactivity ◽  
Serological Tests ◽  
Modelling Studies ◽  
Reliability And Robustness ◽  
Positive Results

The world is going through the scourge of COVID-19 pandemic since last several months. The pandemic appears to be less severe in highly Dengue endemic countries. Furthermore, COVID-19 in two elderly patients (with no evidence of Dengue virus (DV) infection) elicited antibodies that gave false-positive results in DV serological tests. We anticipated that SARS-CoV-2 and DV share antigenic similarity and performed molecular docking studies. Our computational modelling studies predicted that human anti-DV antibodies can indeed, bind to RBD of SARS-CoV-2 Spike protein. Some of these interactions can also potentially intercept human ACE2 receptor binding to RBM. Our computational analysis showed that m396 Ab (against SARS-CoV-1) did not dock with RBM of SARS-CoV-2, a fact already proven experimentally. This confirmed reliability and robustness of our approach. So, immunological memory to DV in endemic countries is thwarting COVID-19. Available Dengue vaccines can be repurposed against SARS-CoV-2 in DV non-endemic countries until approved vaccines/ antivirals become available against COVID-19. Based on the observations that COVID-19 and Dengue severity maps do not tend to overlap and the fact that serological cross-reactivity has been reported for COVID-19 antibodies with Dengue antigen (s), together with results from our computational studies, it is imperative that serology-based diagnosis should be complemented with NAT/virus antigen detection-based tests for definitive diagnosis of either disease in regions where both of these viruses are now co-existent. Furthermore, we still do not know whether antibodies to SARS-CoV-2 will hinder/ameliorate DV infections by binding to DV particles and reduce dengue incidences in the future or, augment DV infection and severity by means of antibody-dependent enhancement (ADE).

scholarly journals Ability To Serologically Confirm Recent Zika Virus Infection in Areas with Varying Past Incidence of Dengue Virus Infection in the United States and U.S. Territories in 2016

2017 ◽  
Vol 56 (1) ◽  
Author(s):  
Nicole P. Lindsey ◽  
J. Erin Staples ◽  
Krista Powell ◽  
Ingrid B. Rabe ◽  
Marc Fischer ◽  
...  
Keyword(s):  
Puerto Rico ◽  
Virus Infection ◽  
Dengue Virus ◽  
Zika Virus ◽  
Denv Infection ◽  
The United States ◽  
American Samoa ◽  
Cross Reactivity ◽  
Immunoglobulin M ◽  
Positive Results

ABSTRACTCross-reactivity within flavivirus antibody assays, produced by shared epitopes in the envelope proteins, can complicate the serological diagnosis of Zika virus (ZIKAV) infection. We assessed the utility of the plaque reduction neutralization test (PRNT) to confirm recent ZIKAV infections and rule out misleading positive immunoglobulin M (IgM) results in areas with various levels of past dengue virus (DENV) infection incidence. We reviewed PRNT results of sera collected for diagnosis of ZIKAV infection from 1 January through 31 August 2016 with positive ZIKAV IgM results, and ZIKAV and DENV PRNTs were performed. PRNT result interpretations included ZIKAV, unspecified flavivirus, DENV infection, or negative. For this analysis, ZIKAV IgM was considered false positive for samples interpreted as a DENV infection or negative. In U.S. states, 208 (27%) of 759 IgM-positive results were confirmed to be ZIKAV compared to 11 (21%) of 52 in the U.S. Virgin Islands (USVI), 15 (15%) of 103 in American Samoa, and 13 (11%) of 123 in Puerto Rico. In American Samoa and Puerto Rico, more than 80% of IgM-positive results were unspecified flavivirus infections. The false-positivity rate was 27% in U.S. states, 18% in the USVI, 2% in American Samoa, and 6% in Puerto Rico. In U.S. states, the PRNT provided a virus-specific diagnosis or ruled out infection in the majority of IgM-positive samples. Almost a third of ZIKAV IgM-positive results were not confirmed; therefore, providers and patients must understand that IgM results are preliminary. In territories with historically higher rates of DENV transmission, the PRNT usually could not differentiate between ZIKAV and DENV infections.

scholarly journals Demonstrating the presence of Ehrlichia canis DNA from different tissues of dogs with suspected subclinical ehrlichiosis

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Carlos A. Rodríguez-Alarcón ◽  
Diana M. Beristain-Ruiz ◽  
Angélica Olivares-Muñoz ◽  
Andrés Quezada-Casasola ◽  
Federico Pérez-Casio ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Lymph Node ◽  
Cross Reactivity ◽  
Ehrlichia Canis ◽  
Serological Tests ◽  
Blood Samples ◽  
Negative Results ◽  
Target Organs ◽  
Polymerase Chain ◽  
Positive Results

Abstract Background Nowadays, Ehrlichia canis receives increasing attention because of its great morbidity and mortality in animals. Dogs in the subclinical and chronic phases can be asymptomatic, and serological tests show cross-reactivity and fail to differentiate between current and past infections. Moreover, there could be low parasitaemia, and E. canis might be found only in target organs, hence causing results to be negative by polymerase chain reaction (PCR) on blood samples. Methods We evaluated by PCR the prevalence of E. canis in blood, liver, spleen, lymph node and bone marrow samples of 59 recently euthanised dogs that had ticks but were clinically healthy. Results In total, 52.55% of the blood PCRs for E. canis were negative, yet 61.30% yielded positive results from tissue biopsies and were as follows: 63.15% from bone marrow; 52.63% from liver; 47.36% from spleen; and 15.78% from lymph node. In addition, 33% had infection in three tissues (spleen, liver and bone marrow). Conclusions Our results show the prevalence of E. canis from tissues of dogs that were negative by blood PCR. Ehrlichia canis DNA in tissue was 30% lower in dogs that tested negative in PCR of blood samples compared to those that were positive. However, it must be taken into account that some dogs with negative results were positive for E. canis in other tissues.

scholarly journals Development of Envelope Protein Antigens To Serologically Differentiate Zika Virus Infection from Dengue Virus Infection

2017 ◽  
Vol 56 (3) ◽  
Author(s):  
Lakshmanane Premkumar ◽  
Matthew Collins ◽  
Stephen Graham ◽  
Guei-Jiun Alice Liou ◽  
Cesar A. Lopez ◽  
...  
Keyword(s):  
Virus Infection ◽  
Dengue Virus ◽  
Zika Virus ◽  
Envelope Protein ◽  
Population Level ◽  
Denv Infection ◽  
Cross Reactivity ◽  
Protein Antigens ◽  
Zikv Infection ◽  
Serological Tests

ABSTRACT Zika virus (ZIKV) is an emerging flavivirus that can cause birth defects and neurologic complications. Molecular tests are effective for diagnosing acute ZIKV infection, although the majority of infections produce no symptoms at all or present after the narrow window in which molecular diagnostics are dependable. Serology is a reliable method for detecting infections after the viremic period; however, most serological assays have limited specificity due to cross-reactive antibodies elicited by flavivirus infections. Since ZIKV and dengue virus (DENV) widely cocirculate, distinguishing ZIKV infection from DENV infection is particularly important for diagnosing individual cases or for surveillance to coordinate public health responses. Flaviviruses also elicit type-specific antibodies directed to non-cross-reactive epitopes of the infecting virus; such epitopes are attractive targets for the design of antigens for development of serological tests with greater specificity. Guided by comparative epitope modeling of the ZIKV envelope protein, we designed two recombinant antigens displaying unique antigenic regions on domain I (Z-EDI) and domain III (Z-EDIII) of the ZIKV envelope protein. Both the Z-EDI and Z-EDIII antigens consistently detected ZIKV-specific IgG in ZIKV-immune sera but not cross-reactive IgG in DENV-immune sera in late convalescence (>12 weeks postinfection). In contrast, during early convalescence (2 to 12 weeks postinfection), secondary DENV-immune sera and some primary DENV-immune sera cross-reacted with the Z-EDI and Z-EDIII antigens. Analysis of sequential samples from DENV-immune individuals demonstrated that Z-EDIII cross-reactivity peaked in early convalescence and declined steeply over time. The Z-EDIII antigen has much potential as a diagnostic antigen for population-level surveillance and for detecting past infections in patients.

scholarly journals Real-time PCR for detecting circulating dengue virus in the Guangdong Province of China in 2006

2008 ◽  
Vol 57 (12) ◽  
pp. 1547-1552 ◽  
Author(s):  
Zhijun Bai ◽  
Licheng Liu ◽  
Zeng Tu ◽  
Lisi Yao ◽  
Jianwei Liu ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Real Time ◽  
Real Time Pcr ◽  
Cross Reactivity ◽  
Clinical Samples ◽  
Sequencing Analysis ◽  
Serum Samples ◽  
Serological Tests ◽  
Wide Range ◽  
Pcr Assays

Dengue virus (DENV) causes a wide range of diseases in humans, from the acute febrile illness dengue fever (DF) to life-threatening dengue haemorrhagic fever/dengue shock syndrome. We developed four real-time quantitative PCR assays for each serotype of DENV based on computational analysis. These assays had high sensitivity and specificity without cross-reactivity for the four serotypes. To evaluate the performance of these assays in detecting and typing the virus in clinical samples, we analysed 64 serum samples from Guangdong during 2006. The results showed that 71 % of those samples were positive by the DEN-1 assay. The DENV assay results, in agreement with the serological tests and sequencing analysis, showed that the pathogen resulting in the DF explosion in Guangdong in 2006 belonged to DEN-1. Compared to the serological assays, the real-time PCR assays that we developed were much more sensitive in the 1–3 days after onset of the symptoms.

scholarly journals Identification of Immunogenic Candidate for New Serological Tests for Brucella melitensis by a Proteomic Approach

2021 ◽  
Vol 15 (1) ◽  
pp. 92-97
Author(s):  
Valentina Paci ◽  
Pierina Visciano ◽  
Ivanka Krasteva ◽  
Tiziana Di Febo ◽  
Fabrizia Perletta ◽  
...  
Keyword(s):  
Brucella Melitensis ◽  
Cross Reactivity ◽  
Protein Antigens ◽  
Serological Tests ◽  
Gram Negative ◽  
Additional Tool ◽  
Bioinformatic Tools ◽  
Proteomic Approach ◽  
Immunogenic Proteins ◽  
Positive Results

Background: The diagnosis of brucellosis by serological tests is based on antigen suspensions derived from smooth lipopolysaccharide extracts, which can give false positive results linked to cross-reactivity with other Gram-negative microorganisms, especially Yersinia enterocolitica O:9 and Escherichia coli O157:H7. Objective: The objective of the present study was the characterization by proteomic analysis of specific immunogenic proteins not associated with smooth lipopolysaccharide to improve the diagnostic tests used in the ovine brucellosis eradication programs. Methods: The serum from a sheep positive to Brucella melitensis was treated to eliminate all antibodies against such lipopolysaccharide and highlight the reaction towards the immunoreactive proteins in Western Blotting. Results: The immunoreactive bands were identified by nLC-MS/MS and through bioinformatic tools, it was possible to select 12 potential candidates as protein antigens specific for Brucella melitensis. Conclusion: The detection of new antigens not subjected to cross-reactivity with other Gram-negative microorganisms can offer an additional tool for the serological diagnosis of such disease.

Improving the Sensitivity and the Specificity of HLA-B27 Typing by Replacing Serological Tests with a TaqMan-PCR Assay

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4720-4720
Author(s):  
Xiaoduan Weng ◽  
Louise Robin ◽  
Marie-lise Audet ◽  
Linda Hébert ◽  
Ginette Lapointe ◽  
...  
Keyword(s):  
Detection System ◽  
Cross Reactivity ◽  
Hla B27 ◽  
Serological Tests ◽  
Dna Assay ◽  
Negative Results ◽  
Flow Cytometric ◽  
Antigen Assay ◽  
Taqman Pcr ◽  
Positive Results

Abstract HLA-B27 is a strong diagnostic biomarker as it is found in 90– 95% of ankylosing spondylitis. Routinely, the false-positive results generated by cross-reactivity of HLA-B27 monoclonal antibodies (mAbs) with some other type of HLA-B antigens are problematic. The present study aims at improving the sensitivity and specificity of typing for HLA-B27 by using a more accurate DNA assay. A real time sequence specific primer polymerase chain reaction (PCR-SSP) is performed by using MGB TaqMan oligoprobe and an ABI PRISM™ 7500 sequence detection system. The TaqMan PCR-SSP assay is compared with Immunophenotyping by flow cytometric antigen assay (BD HLA-B27-Kit, clone GS145.2). The results are finally confirmed by sequencing (ABI PRISM ® 3100). As summarised in the table, three methods are identical for clearly positive and negative results. There is 90% concordance for borderline negative results obtained by immunophenotyping with TaqMan PCR-SSC and/or sequencing. However, only 15.4% of borderline positives obtained by immunophenotyping are confirmed as true HLA-B27 positives by sequencing as well as TaqMan PCR-SSC. TaqMan PCR-SSP DNA assay completely correlates with sequencing (gold standard) with 100% PPV and NPV, compared to a PPV of 15% and a NPV of 98% for borderline results by immunophenotyping. Conclusion: when compared with flow cytometric antigen assay, typing HLA-B27 by TaqMan PCR-SSP clearly demonstrates an advantage to better establish the genotype of the patient. Specifically, there is a marked difference for ambitious positive results from immunophenotyping. Moreover, compared to immunophenotyping, there is no need of fresh samples, can test a larger number of samples concomitantly, and reduces technical time as well as cost. N = 52 Immunophenotyping TaqMan PCR-SSP Sequencing Immuno vs Sequencing TaqMan PCR-SSP vs Sequencing Positive 11 11 11 100% 100% Negative 17 17 17 100% 100% Positive (borderline by Immunophenotyping) 13 2 2 15% 100% Negative (borderline ) by Immunophenotyping) 10 9 9 98% 100%

scholarly journals Demonstrating the presence of Ehrlichia canis DNA from different tissues of dogs with negative PCR in blood

2020 ◽  
Author(s):  
Carlos Arturo Rodríguez-Alarcón ◽  
Diana M. Beristain-Ruiz ◽  
Angélica Olivares-Muñoz ◽  
Andrés Quezada-Casasola ◽  
Federico Pérez-Casio ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Lymph Node ◽  
Cross Reactivity ◽  
Ehrlichia Canis ◽  
Serological Tests ◽  
Blood Samples ◽  
Negative Results ◽  
Target Organs ◽  
Polymerase Chain ◽  
Positive Results

Abstract Background: Nowadays, Ehrlichia canis receives increasing attention because of its great morbidity and mortality in animals. Dogs in the subclinical and chronic phases can be asymptomatic, and serological tests show cross-reactivity and fail to differentiate between current and past infections. Moreover, there could be low parasitaemia, and E. canis might be found only in target organs, hence causing results to be negative by polymerase chain reaction (PCR) on blood samples.Methods: We evaluated by PCR the prevalence of E. canis in blood, liver, spleen, lymph node and bone marrow samples of 59 recently euthanised dogs that had ticks but were clinically healthy.Results: In total, 52.55% of the blood PCRs for E. canis were negative, yet 61.30% yielded positive results from tissue biopsies and were as follows: 63.15% from bone marrow; 52.63% from liver; 47.36% from spleen; and 15.78% from lymph node. In addition, 33% had infection in three tissues (spleen, liver and bone marrow).Conclusions: Our results show the prevalence of E. canis from tissues of dogs that were negative by blood PCR. Ehrlichia canis DNA in tissue was 30% lower in dogs that tested negative in PCR of blood samples compared to those that were positive. However, it must be taken into account that some dogs with negative results were positive for E. canis in other tissues.

Enterovirus D-68 Molecular Virology, Epidemiology, and Treatment: an update and way forward

2020 ◽  
Vol 20 ◽  
Author(s):  
Mahmoud Ahmed Ebada ◽  
Notila Fayed ◽  
Souad Alkanj ◽  
Ahmed Wadaa Allah
Keyword(s):  
Current Knowledge ◽  
Rna Virus ◽  
Neurological Diseases ◽  
Cross Reactivity ◽  
Serological Tests ◽  
Molecular Virology ◽  
Acute Flaccid Myelitis ◽  
The Family ◽  
Pcr Products ◽  
Enterovirus D68

: Enterovirus D68 (EV-D68) is a single-stranded positive-sense RNA virus, and it is one of the family Picornaviridae. Except for EV-D68, the family Picornaviridae has been illustrated in literature. EV-D68 was first discovered and isolated in California, USA, in 1962. EV-D68 has resulted in respiratory disorders’ outbreaks among children worldwide, and it has been detected in cases of various neurological diseases such as acute flaccid myelitis (AFM). A recent study documented a higher number of EV-D68 cases associated with AFM in Europe in 2016 compared to the 2014 outbreak. EV-D68 is mainly diagnosed by quantitative PCR, and there is an affirmative strategy for EV-D68 detection by using pan-EV PCR on the untranslated region and/or the VP1 or VP2, followed by sequencing of the PCR products. Serological tests are limited due to cross-reactivity of the antigens between the different serotypes. Many antiviral drugs for EV-D68 have been evaluated, and showed promising results. In our review, we discuss the current knowledge about EV-D68 and its role in the development of AFM.

scholarly journals A High-Performance Multiplex Immunoassay for Serodiagnosis of Flavivirus-Associated Neurological Diseases in Horses

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Cécile Beck ◽  
Philippe Desprès ◽  
Sylvie Paulous ◽  
Jessica Vanhomwegen ◽  
Steeve Lowenski ◽  
...  
Keyword(s):  
High Performance ◽  
Neurological Diseases ◽  
Expression System ◽  
Cross Reactivity ◽  
Encephalitis Virus ◽  
Serological Tests ◽  
Multiplex Immunoassay ◽  
Tick Borne Encephalitis ◽  
Tick Borne Encephalitis Virus ◽  
Negative Controls

West Nile virus (WNV), Japanese encephalitis virus (JEV), and tick-borne encephalitis virus (TBEV) are flaviviruses responsible for severe neuroinvasive infections in humans and horses. The confirmation of flavivirus infections is mostly based on rapid serological tests such as enzyme-linked immunosorbent assays (ELISAs). These tests suffer from poor specificity, mainly due to antigenic cross-reactivity among flavivirus members. Robust diagnosis therefore needs to be validated through virus neutralisation tests (VNTs) which are time-consuming and require BSL3 facilities. The flavivirus envelope (E) glycoprotein ectodomain is composed of three domains (D) named DI, DII, and DIII, with EDIII containing virus-specific epitopes. In order to improve the serological differentiation of flavivirus infections, the recombinant soluble ectodomain of WNV E (WNV.sE) and EDIIIs (rEDIIIs) of WNV, JEV, and TBEV were synthesised using theDrosophilaS2 expression system. Purified antigens were covalently bonded to fluorescent beads. The microspheres coupled to WNV.sE or rEDIIIs were assayed with about 300 equine immune sera from natural and experimental flavivirus infections and 172 nonimmune equine sera as negative controls. rEDIII-coupled microspheres captured specific antibodies against WNV, TBEV, or JEV in positive horse sera. This innovative multiplex immunoassay is a powerful alternative to ELISAs and VNTs for veterinary diagnosis of flavivirus-related diseases.

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