scholarly journals Identification of Five Interferon-Induced Cellular Proteins That Inhibit West Nile Virus and Dengue Virus Infections

2010 ◽  
Vol 84 (16) ◽  
pp. 8332-8341 ◽  
Author(s):  
Dong Jiang ◽  
Jessica M. Weidner ◽  
Min Qing ◽  
Xiao-Ben Pan ◽  
Haitao Guo ◽  
...  
Keyword(s):  
West Nile Virus ◽  
Antiviral Activity ◽  
Dengue Virus ◽  
Denv Infection ◽  
Life Cycles ◽  
Hek293 Cells ◽  
Virus Infections ◽  
West Nile ◽  
Antiviral Immune Response ◽  
Cell Plasma

ABSTRACT Interferons (IFNs) are key mediators of the host innate antiviral immune response. To identify IFN-stimulated genes (ISGs) that instigate an antiviral state against two medically important flaviviruses, West Nile virus (WNV) and dengue virus (DENV), we tested 36 ISGs that are commonly induced by IFN-α for antiviral activity against the two viruses. We discovered that five ISGs efficiently suppressed WNV and/or DENV infection when they were individually expressed in HEK293 cells. Mechanistic analyses revealed that two structurally related cell plasma membrane proteins, IFITM2 and IFITM3, disrupted early steps (entry and/or uncoating) of the viral infection. In contrast, three IFN-induced cellular enzymes, viperin, ISG20, and double-stranded-RNA-activated protein kinase, inhibited steps in viral proteins and/or RNA biosynthesis. Our results thus imply that the antiviral activity of IFN-α is collectively mediated by a panel of ISGs that disrupt multiple steps of the DENV and WNV life cycles.

scholarly journals Surveillance of the major pathogenic arboviruses of public health concern in Gabon, Central Africa: increased risk of West Nile virus and dengue virus infections

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yuri Ushijima ◽  
Haruka Abe ◽  
Georgelin Nguema Ondo ◽  
Rodrigue Bikangui ◽  
Marguerite Massinga Loembé ◽  
...  
Keyword(s):  
Public Health ◽  
West Nile Virus ◽  
Dengue Virus ◽  
Central Africa ◽  
Fever Virus ◽  
Health Concern ◽  
Virus Infections ◽  
Public Health Concern ◽  
Serum Samples ◽  
West Nile

Abstract Background Increasing arbovirus infections have been a global burden in recent decades. Many countries have experienced the periodic emergence of arbovirus diseases. However, information on the prevalence of arboviruses is largely unknown or infrequently updated because of the lack of surveillance studies, especially in Africa. Methods A surveillance study was conducted in Gabon, Central Africa, on arboviruses, which are a major public health concern in Africa, including: West Nile virus (WNV), dengue virus (DENV), Zika virus (ZIKV), yellow fever virus (YFV), chikungunya virus (CHIKV), and Rift Valley fever virus (RVFV). Serological and molecular assays were performed to investigate past infection history and the current status of infection, using serum samples collected from healthy individuals and febrile patients, respectively. Results The overall seroprevalence during 2014˗2017 was estimated to be 25.3% for WNV, 20.4% for DENV, 40.3% for ZIKV, 60.7% for YFV, 61.2% for CHIKV, and 14.3% for RVFV. No significant differences were found in the seroprevalence of any of the viruses between the male and female populations. However, a focus on the mean age in each arbovirus-seropositive individual showed a significantly younger age in WNV- and DENV-seropositive individuals than in CHIKV-seropositive individuals, indicating that WNV and DENV caused a relatively recent epidemic in the region, whereas CHIKV had actively circulated before. Of note, this indication was supported by the detection of both WNV and DENV genomes in serum samples collected from febrile patients after 2016. Conclusions This study revealed the recent re-emergence of WNV and DENV in Gabon as well as the latest seroprevalence state of the major arboviruses, which indicated the different potential risks of virus infections and virus-specific circulation patterns. This information will be helpful for public health organizations and will enable a rapid response towards these arbovirus infections, thereby preventing future spread in the country.

scholarly journals Evaluation of an Epitope-Blocking Enzyme-Linked Immunosorbent Assay for the Diagnosis of West Nile Virus Infections in Humans

2009 ◽  
Vol 16 (5) ◽  
pp. 749-755 ◽  
Author(s):  
M. A. Loroño-Pino ◽  
J. A. Farfan-Ale ◽  
B. J. Blitvich ◽  
J. L. Beebe ◽  
R. G. Jarman ◽  
...  
Keyword(s):  
West Nile Virus ◽  
Dengue Virus ◽  
Immunosorbent Assay ◽  
False Positive ◽  
False Positive Rate ◽  
Enzyme Linked Immunosorbent Assay ◽  
Virus Infections ◽  
Characteristic Analysis ◽  
West Nile ◽  
Positive Rate

ABSTRACT An epitope-blocking enzyme-linked immunosorbent assay (b-ELISA) was evaluated for the diagnosis of West Nile virus (WNV) infections in humans. Sera from patients diagnosed with WNV infections from an outbreak in 2003 in Colorado and from patients diagnosed with dengue virus infections from Mexico and Thailand were tested with the b-ELISA. The b-ELISAs were performed using the WNV-specific monoclonal antibody (MAb) 3.1112G and the flavivirus-specific MAb 6B6C-1. Although the WNV-specific b-ELISA was effective in diagnosing WNV infections in humans from Colorado, it was not efficacious for diagnosing WNV infections in serum specimens from Mexico and Thailand. In serum specimens from patients from Colorado, the WNV b-ELISA and the WNV plaque reduction neutralization test showed an overall agreement of 91%. The sensitivity and specificity of the WNV b-ELISA were 89% and 92%, respectively, with a false-positive rate of 5%, based on receiver operating characteristic analysis. In contrast, false-positive rate results in specimens from the countries of Mexico and Thailand, where flaviviruses are endemic, were 79% and 80%, presumably due to the presence of antibodies resulting from previous dengue virus infections in Mexico and/or Japanese encephalitis virus infections or vaccination in Thailand. Thus, in regions where people have experienced previous or multiple flavivirus infections, the use of the b-ELISA for WNV diagnosis is contraindicated.

scholarly journals Human MicroRNA miR-532-5p Exhibits Antiviral Activity against West Nile Virus via Suppression of Host Genes SESTD1 and TAB3 Required for Virus Replication

2015 ◽  
Vol 90 (5) ◽  
pp. 2388-2402 ◽  
Author(s):  
Andrii Slonchak ◽  
Rory P. Shannon ◽  
Gabor Pali ◽  
Alexander A. Khromykh
Keyword(s):  
West Nile Virus ◽  
Antiviral Response ◽  
Human Cells ◽  
Hek293 Cells ◽  
Type I ◽  
Virus Infections ◽  
West Nile ◽  
Viral Pathogen ◽  
Host Genes

ABSTRACTWest Nile virus (WNV) is a mosquito-transmitted flavivirus that naturally circulates between mosquitos and birds but can also infect humans, causing severe neurological disease. The early host response to WNV infection in vertebrates primarily relies on the type I interferon pathway; however, recent studies suggest that microRNAs (miRNAs) may also play a notable role. In this study, we assessed the role of host miRNAs in response to WNV infection in human cells. We employed small RNA sequencing (RNA-seq) analysis to determine changes in the expression of host miRNAs in HEK293 cells infected with an Australian strain of WNV, Kunjin (WNVKUN), and identified a number of host miRNAs differentially expressed in response to infection. Three of these miRNAs were confirmed to be significantly upregulated in infected cells by quantitative reverse transcription (qRT)-PCR and Northern blot analyses, and one of them, miR-532-5p, exhibited a significant antiviral effect against WNVKUNinfection. We have demonstrated that miR-532-5p targets and downregulates expression of the host genes SESTD1 and TAB3 in human cells. Small interfering RNA (siRNA) depletion studies showed that both SESTD1 and TAB3 were required for efficient WNVKUNreplication. We also demonstrated upregulation of mir-532-5p expression and a corresponding decrease in the expression of its targets, SESTD1 and TAB3, in the brains of WNVKUN-infected mice. Our results show that upregulation of miR-532-5p and subsequent suppression of the SESTD1 and TAB3 genes represent a host antiviral response aimed at limiting WNVKUNinfection and highlight the important role of miRNAs in controlling RNA virus infections in mammalian hosts.IMPORTANCEWest Nile virus (WNV) is a significant viral pathogen that poses a considerable threat to human health across the globe. There is no specific treatment or licensed vaccine available for WNV, and deeper insight into how the virus interacts with the host is required to facilitate their development. In this study, we addressed the role of host microRNAs (miRNAs) in antiviral response to WNV in human cells. We identified miR-532-5p as a novel antiviral miRNA and showed that it is upregulated in response to WNV infection and suppresses the expression of the host genes TAB3 and SESTD1 required for WNV replication. Our results show that upregulation of miR-532-5p and subsequent suppression of the SESTD1 and TAB3 genes represent an antiviral response aimed at limiting WNV infection and highlight the important role of miRNAs in controlling virus infections in mammalian hosts.

scholarly journals Dengue Virus NS Proteins Inhibit RIG-I/MAVS Signaling by Blocking TBK1/IRF3 Phosphorylation: Dengue Virus Serotype 1 NS4A Is a Unique Interferon-Regulating Virulence Determinant

mBio ◽  
2015 ◽  
Vol 6 (3) ◽  
Author(s):  
Nadine A. Dalrymple ◽  
Velasco Cimica ◽  
Erich R. Mackow
Keyword(s):  
West Nile Virus ◽  
Dengue Virus ◽  
Interferon Beta ◽  
Denv Infection ◽  
Type I ◽  
West Nile ◽  
Virulence Determinant ◽  
Virus Serotype ◽  
Serotype 1 ◽  
Viral Attenuation

ABSTRACTDengue virus (DENV) replication is inhibited by the prior addition of type I interferon or by RIG-I agonists that elicit RIG-I/MAVS/TBK1/IRF3-dependent protective responses. DENV infection of primary human endothelial cells (ECs) results in a rapid increase in viral titer, which suggests that DENV inhibits replication-restrictive RIG-I/interferon beta (IFN-β) induction pathways within ECs. Our findings demonstrate that DENV serotype 4 (DENV4) nonstructural (NS) proteins NS2A and NS4B inhibited RIG-I-, MDA5-, MAVS-, and TBK1/IKKε-directed IFN-β transcription (>80%) but failed to inhibit IFN-β induction directed by STING or constitutively active IRF3-5D. Expression of NS2A and NS4B dose dependently inhibited the phosphorylation of TBK1 and IRF3, which suggests that they function at the level of TBK1 complex activation. NS2A and NS4B from DENV1/2/4, as well as the West Nile virus NS4B protein, commonly inhibited TBK1 phosphorylation and IFN-β induction. A comparative analysis of NS4A proteins across DENVs demonstrated that DENV1, but not DENV2 or DENV4, NS4A proteins uniquely inhibited TBK1. These findings indicate that DENVs contain conserved (NS2A/NS4B) and DENV1-specific (NS4A) mechanisms for inhibiting RIG-I/TBK1-directed IFN responses. Collectively, our results define DENV NS proteins that restrict IRF3 and IFN responses and thereby facilitate DENV replication and virulence. Unique DENV1-specific NS4A regulation of IFN induction has the potential to be a virulence determinant that contributes to the increased severity of DENV1 infections and the immunodominance of DENV1 responses during tetravalent DENV1-4 vaccination.IMPORTANCEOur findings demonstrate that NS2A and NS4B proteins from dengue virus serotypes 1, 2, and 4 are inhibitors of RIG-I/MDA5-directed interferon beta (IFN-β) induction and that they accomplish this by blocking TBK1 activation. We determined that IFN inhibition is functionally conserved across NS4B proteins from West Nile virus and DENV1, -2, and -4 viruses. In contrast, DENV1 uniquely encodes an extra IFN regulating protein, NS4A, that inhibits TBK1-directed IFN induction. DENV1 is associated with an increase in severe patient disease, and added IFN regulation by the DENV1 NS4A protein may contribute to increased DENV1 replication, immunodominance, and virulence. The regulation of IFN induction by nonstructural (NS) proteins suggests their potential roles in enhancing viral replication and spread and as potential protein targets for viral attenuation. DENV1-specific IFN regulation needs to be considered in vaccine strategies where enhanced DENV1 replication may interfere with DENV2-4 seroconversion within coadministered tetravalent DENV1-4 vaccines.

Identification of anti-premembrane antibody as a serocomplex-specific marker to discriminate Zika, dengue and West Nile virus infections

2021 ◽  
Author(s):  
Szu-Chia Hsieh ◽  
Wen-Yang Tsai ◽  
Jih-Jin Tsai ◽  
Mars Stone ◽  
Graham Simmons ◽  
...  
Keyword(s):  
West Nile Virus ◽  
Nonstructural Protein ◽  
Denv Infection ◽  
Antibody Responses ◽  
Severe Dengue ◽  
Specific Marker ◽  
Virus Infections ◽  
West Nile ◽  
Serological Tests ◽  
Nonstructural Protein 1

Although transmission of Zika virus (ZIKV) in the Americas has greatly declined since late 2017, recent reports of reduced risks of symptomatic Zika by prior dengue virus (DENV) infection and increased risks of severe dengue disease by previous ZIKV or DENV infection underscore a critical need for serological tests that can discriminate past ZIKV, DENV and/or other flavivirus infections and improve our understanding of the immune interactions between these viruses and vaccine strategy in endemic regions. As serological tests for ZIKV primarily focus on envelope (E) and nonstructural protein 1 (NS1), antibodies to other ZIKV proteins have not been explored. Here we employed Western blot analysis using antigens of 6 flaviviruses from 3 serocomplexes to investigate antibody responses following reverse-transcription-polymerase-chain reaction-confirmed ZIKV infection. Panels of 20 primary ZIKV and 20 ZIKV with previous DENV infection recognized E proteins of all 6 flaviviruses and NS1 protein of ZIKV with some cross-reactivity to DENV. While the primary ZIKV panel recognized only the premembrane (prM) protein of ZIKV, the ZIKV with previous DENV panel recognized both ZIKV and DENV prM proteins. Analysis of antibody responses following 42 DENV and 18 West Nile virus infections revealed similar patterns of recognition by anti-E and anti-NS1 antibodies, whereas both panels recognized prM protein of homologous serocomplex but not others. The specificity was further supported by analysis of sequential samples. Together, these findings suggest that anti-prM antibody is a flavivirus serocomplex-specific marker and can be used to delineate current and past flavivirus infections in endemic areas. IMPORTANCE Despite a decline in Zika virus (ZIKV) transmission since late 2017, questions regarding its surveillance, potential re-emergence, and interactions with other flaviviruses in endemic regions remain unanswered. Recent studies have reported reduced risks of symptomatic Zika by prior dengue virus (DENV) infection and increased risks of severe dengue disease by previous ZIKV or DENV infection, highlighting a need for better serological tests to discriminate past ZIKV, DENV and/or other flavivirus infections and improved understanding of the immune interactions and vaccine strategy for these viruses. As most serological tests for ZIKV focused on envelope and nonstructural protein 1, antibodies to other ZIKV proteins including potentially specific antibodies remain understudied. We employed Western blot analysis using antigens of 6 flaviviruses to study antibody responses following well-documented ZIKV, DENV and West Nile virus infections and identified anti-premembrane antibody as a flavivirus serocomplex-specific marker to delineate current and past flavivirus infections in endemic areas.

scholarly journals Epidemiology of West Nile Virus Infections in Humans, Italy, 2012–2020: A Summary of Available Evidences

2021 ◽  
Vol 6 (2) ◽  
pp. 61
Author(s):  
Matteo Riccò ◽  
Simona Peruzzi ◽  
Federica Balzarini
Keyword(s):  
West Nile Virus ◽  
Age Groups ◽  
Invasive Disease ◽  
Incidence Rates ◽  
Annual Incidence ◽  
Virus Infections ◽  
West Nile ◽  
Po River ◽  
Air Temperatures ◽  
Sex Risk

In Italy, human cases of West Nile virus (WNV) infection have been recorded since 2008, and seasonal outbreaks have occurred almost annually. In this study, we summarize available evidences on the epidemiology of WNV and West Nile neuro-invasive disease (WNND) in humans reported between 2012 and 2020. In total, 1145 WNV infection cases were diagnosed; of them 487 (42.5%) had WNND. A significant circulation of the pathogen was suggested by studies on blood donors, with annual incidence rates ranging from 1.353 (95% confidence intervals (95% CI) 0.279–3.953) to 19.069 cases per 100,000 specimens (95% CI 13.494–26.174). The annual incidence rates of WNND increased during the study period from 0.047 cases per 100,000 (95% CI 0.031–0.068) in 2012, to 0.074 cases per 100,000 (95% CI 0.054–0.099) in 2020, peaking to 0.377 cases per 100,000 (95% CI 0.330–0.429) in 2018. There were 60 deaths. Cases of WNND were clustered in Northern Italy, particularly in the Po River Valley, during the months of August (56.7%) and September (27.5%). Higher risk for WNND was reported in subjects of male sex (risk ratio (RR) 1.545, 95% CI 1.392–1.673 compared to females), and in older age groups (RR 24.46, 95% CI 15.61–38.32 for 65–74 y.o.; RR 43.7, 95% CI 28.33–67.41 for subjects older than 75 years), while main effectors were identified in average air temperatures (incidence rate ratio (IRR) 1.3219, 95% CI 1.0053–1.7383), population density (IRR 1.0004, 95% CI 1.0001–1.0008), and occurrence of cases in the nearby provinces (IRR 1.0442, 95% CI 1.0340–1.0545). In summary, an enhanced surveillance is vital for the early detection of human cases and the prompt implementation of response measures.

scholarly journals The IFITM Proteins Mediate Cellular Resistance to Influenza A H1N1 Virus, West Nile Virus, and Dengue Virus

Cell ◽  
2009 ◽  
Vol 139 (7) ◽  
pp. 1243-1254 ◽  
Author(s):  
Abraham L. Brass ◽  
I-Chueh Huang ◽  
Yair Benita ◽  
Sinu P. John ◽  
Manoj N. Krishnan ◽  
...  
Keyword(s):  
West Nile Virus ◽  
Dengue Virus ◽  
Influenza A ◽  
H1n1 Virus ◽  
West Nile ◽  
Cellular Resistance ◽  
Influenza A H1n1 ◽  
Virus West Nile

scholarly journals Environmental Predictors of Human West Nile Virus Infections, Colorado

2007 ◽  
Vol 13 (11) ◽  
pp. 1788-1790 ◽  
Author(s):  
Jennifer L. Patnaik ◽  
Lara Juliusson ◽  
Richard L. Vogt
Keyword(s):  
West Nile Virus ◽  
Virus Infections ◽  
Environmental Predictors ◽  
West Nile ◽  
Human West Nile Virus

scholarly journals Increase in human West Nile and Usutu virus infections, Austria, 2018

2018 ◽  
Vol 23 (43) ◽  
Author(s):  
Stephan W. Aberle ◽  
Jolanta Kolodziejek ◽  
Christof Jungbauer ◽  
Karin Stiasny ◽  
Judith H. Aberle ◽  
...  
Keyword(s):  
West Nile Virus ◽  
Blood Donors ◽  
Blood Donation ◽  
Virus Infections ◽  
West Nile Fever ◽  
West Nile ◽  
Usutu Virus ◽  
Neuroinvasive Disease ◽  
Human West Nile Virus ◽  
Imported Cases

Between 28 June and 17 September 2018, 27 cases of human West Nile virus infections were recorded in Austria; four cases of West Nile neuroinvasive disease, 11 cases of West Nile fever, six infections detected by blood donation screening and six imported cases. In addition, 18 cases of human Usutu virus infections (all blood donors) were recorded. This is the highest number of annual infections recorded in Austria since the introduction of both viruses.

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