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Emerging Infectious Diseases Aug 2016Worldwide, West Nile virus (WNV) causes encephalitis in humans, horses, and birds. The Kunjin strain of WNV (WNVKUN) is endemic to northern Australia, but infections are...
Worldwide, West Nile virus (WNV) causes encephalitis in humans, horses, and birds. The Kunjin strain of WNV (WNVKUN) is endemic to northern Australia, but infections are usually asymptomatic. In 2011, an unprecedented outbreak of equine encephalitis occurred in southeastern Australia; most of the ≈900 reported cases were attributed to a newly emerged WNVKUN strain. To investigate the origins of this virus, we performed genetic analysis and in vitro and in vivo studies of 13 WNVKUN isolates collected from different regions of Australia during 1960-2012. Although no disease was recorded for 1984, 2000, or 2012, isolates collected during those years (from Victoria, Queensland, and New South Wales, respectively) exhibited levels of virulence in mice similar to that of the 2011 outbreak strain. Thus, virulent strains of WNVKUN have circulated in Australia for >30 years, and the first extensive outbreak of equine disease in Australia probably resulted from a combination of specific ecologic and epidemiologic conditions.
Topics: Amino Acid Sequence; Animals; Antibodies, Monoclonal; Antibody Specificity; Antigens, Viral; Australia; Cell Line; Evolution, Molecular; Genome, Viral; Humans; Mice; Virulence; West Nile Fever; West Nile virus
PubMed: 27433830
DOI: 10.3201/eid2208.151719 -
Parasites & Vectors Mar 2017Active vector surveillance provides an efficient tool for monitoring the presence or spread of emerging or re-emerging vector-borne viruses. This study was undertaken to...
BACKGROUND
Active vector surveillance provides an efficient tool for monitoring the presence or spread of emerging or re-emerging vector-borne viruses. This study was undertaken to investigate the circulation of flaviviruses. Mosquitoes were collected from 58 locations in 10 provinces across the Aegean, Thrace and Mediterranean Anatolian regions of Turkey in 2014 and 2015. Following morphological identification, mosquitoes were pooled and screened by nested and real-time PCR assays. Detected viruses were further characterised by sequencing. Positive pools were inoculated onto cell lines for virus isolation. Next generation sequencing was employed for genomic characterisation of the isolates.
RESULTS
A total of 12,711 mosquito specimens representing 15 species were screened in 594 pools. Eleven pools (2%) were reactive in the virus screening assays. Sequencing revealed West Nile virus (WNV) in one Culex pipiens (s.l.) pool from Thrace. WNV sequence corresponded to lineage one clade 1a but clustered distinctly from the Turkish prototype isolate. In 10 pools, insect-specific flaviviruses were characterised as Culex theileri flavivirus in 5 pools of Culex theileri and one pool of Cx. pipiens (s.l.), Ochlerotatus caspius flavivirus in two pools of Aedes (Ochlerotatus) caspius, Flavivirus AV-2011 in one pool of Culiseta annulata, and an undetermined flavivirus in one pool of Uranotaenia unguiculata from the Aegean and Thrace regions. DNA forms or integration of the detected insect-specific flaviviruses were not observed. A virus strain, tentatively named as "Ochlerotatus caspius flavivirus Turkey", was isolated from an Ae. caspius pool in C6/36 cells. The viral genome comprised 10,370 nucleotides with a putative polyprotein of 3,385 amino acids that follows the canonical flavivirus polyprotein organisation. Sequence comparisons and phylogenetic analyses revealed the close relationship of this strain with Ochlerotatus caspius flavivirus from Portugal and Hanko virus from Finland. Several conserved structural and amino acid motifs were identified.
CONCLUSIONS
We identified WNV and several distinct insect-specific flaviviruses during an extensive biosurveillance study of mosquitoes in various regions of Turkey in 2014 and 2015. Ongoing circulation of WNV is revealed, with an unprecedented genetic diversity. A probable replicating form of an insect flavivirus identified only in DNA form was detected.
Topics: Aedes; Animals; Culex; Flavivirus; Flavivirus Infections; Genetic Variation; Genome, Viral; Humans; Insect Vectors; Phylogeny; Species Specificity; Turkey; West Nile Fever; West Nile virus
PubMed: 28320443
DOI: 10.1186/s13071-017-2087-7 -
Veterinary Research Jun 2013West Nile virus (WNV) is a globally distributed arthropod-borne flavivirus capable of infecting a wide variety of vertebrates, with birds as its natural reservoir.... (Review)
Review
West Nile virus (WNV) is a globally distributed arthropod-borne flavivirus capable of infecting a wide variety of vertebrates, with birds as its natural reservoir. Although it had been considered a pathogen of little importance for birds, from the 1990's, and especially after its introduction in the North American continent in 1999, thousands of birds have succumbed to West Nile infection. This review summarizes the pathogenesis and pathology of WNV infection in birds highlighting differences in lesion and antigen distribution and severity among bird orders and families. Despite significant species differences in susceptibility to infection, WNV associated lesions and viral antigen are present in the majority of organs of infected birds. The non-progressive, acute or more prolonged course of the disease accounts for part of the differences in lesion and viral antigen distribution and lesion severity. Most likely a combination of host variables and environmental factors in addition to the intrinsic virulence and pathogenicity of the infecting WNV strain influence the pathogenesis of the infection.
Topics: Animals; Antigens, Viral; Bird Diseases; Birds; Disease Susceptibility; Organ Specificity; Species Specificity; West Nile Fever; West Nile virus
PubMed: 23731695
DOI: 10.1186/1297-9716-44-39 -
Communications Biology Jan 2022It is unclear whether West Nile virus (WNV) circulates endemically in Portugal. Despite the country's adequate climate for transmission, Portugal has only reported four...
It is unclear whether West Nile virus (WNV) circulates endemically in Portugal. Despite the country's adequate climate for transmission, Portugal has only reported four human WNV infections so far. We performed a review of WNV-related data (1966-2020), explored mosquito (2016-2019) and land type distributions (1992-2019), and used climate data (1981-2019) to estimate WNV transmission suitability in Portugal. Serological and molecular evidence of WNV circulation from animals and vectors was largely restricted to the south. Land type and climate-driven transmission suitability distributions, but not the distribution of WNV-capable vectors, were compatible with the North-South divide present in serological and molecular evidence of WNV circulation. Our study offers a comprehensive, data-informed perspective and review on the past epidemiology, surveillance and climate-driven transmission suitability of WNV in Portugal, highlighting the south as a subregion of importance. Given the recent WNV outbreaks across Europe, our results support a timely change towards local, active surveillance.
Topics: Animal Distribution; Animals; Climate; Culicidae; Humans; Mosquito Vectors; Portugal; Seasons; Species Specificity; Weather; West Nile Fever; West Nile virus
PubMed: 35013546
DOI: 10.1038/s42003-021-02969-3 -
Journal of Virology Sep 2017West Nile virus (WNV) is a mosquito-borne flavivirus that causes epidemics of encephalitis and viscerotropic disease worldwide. This virus has spread rapidly and has...
West Nile virus (WNV) is a mosquito-borne flavivirus that causes epidemics of encephalitis and viscerotropic disease worldwide. This virus has spread rapidly and has posed a significant public health threat since the outbreak in New York City in 1999. The interferon (IFN)-mediated antiviral response represents an important component of virus-host interactions and plays an essential role in regulating viral replication. Previous studies have suggested that multifunctional nonstructural proteins encoded by flaviviruses antagonize the host IFN response via various means in order to establish efficient viral replication. In this study, we demonstrated that the nonstructural protein 1 (NS1) of WNV antagonizes IFN-β production, most likely through suppression of retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) activation. In a dual-luciferase reporter assay, WNV NS1 significantly inhibited the activation of the IFN-β promoter after Sendai virus infection or poly(I·C) treatment. NS1 also suppressed the activation of the IFN-β promoter when it was stimulated by interferon regulatory factor 3 (IRF3)/5D or its upstream molecules in the RLR signaling pathway. Furthermore, NS1 blocked the phosphorylation and nuclear translocation of IRF3 upon stimulation by various inducers. Mechanistically, WNV NS1 targets RIG-I and melanoma differentiation-associated gene 5 (MDA5) by interacting with them and subsequently causing their degradation by the proteasome. Furthermore, WNV NS1 inhibits the K63-linked polyubiquitination of RIG-I, thereby inhibiting the activation of downstream sensors in the RLR signaling pathway. Taken together, our results reveal a novel mechanism by which WNV NS1 interferes with the host antiviral response. WNV Nile virus (WNV) has received increased attention since its introduction to the United States. However, the pathogenesis of this virus is poorly understood. This study demonstrated that the nonstructural protein 1 (NS1) of WNV antagonizes the induction of interferon beta (IFN-β) by interacting with and degrading retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5), which are crucial viral sensors in the host innate immune system. Further experiments suggested that NS1-mediated inhibition of the RIG-I-like receptor (RLR) signaling pathway involves inhibition of RIG-I K63-linked polyubiquitination and that the proteasome plays a role in RIG-I degradation. This study provides new insights into the regulation of WNV NS1 in the RLR signaling pathway and reveals a novel mechanism by which WNV evades the host innate immune response. The novel findings may guide us to discover new therapeutic targets and develop effective vaccines for WNV infections.
Topics: Animals; Cell Line; DEAD Box Protein 58; Host-Pathogen Interactions; Humans; Immune Evasion; Interferon-Induced Helicase, IFIH1; Interferon-beta; Proteasome Endopeptidase Complex; Proteolysis; Receptors, Immunologic; Viral Nonstructural Proteins; West Nile virus
PubMed: 28659477
DOI: 10.1128/JVI.02396-16 -
PloS One 2009West Nile virus (WNV) has emerged globally as an increasingly important pathogen for humans and domestic animals. Studies of the evolutionary diversity of the virus over...
West Nile virus (WNV) has emerged globally as an increasingly important pathogen for humans and domestic animals. Studies of the evolutionary diversity of the virus over its known history will help to elucidate conserved sites, and characterize their correspondence to other pathogens and their relevance to the immune system. We describe a large-scale analysis of the entire WNV proteome, aimed at identifying and characterizing evolutionarily conserved amino acid sequences. This study, which used 2,746 WNV protein sequences collected from the NCBI GenPept database, focused on analysis of peptides of length 9 amino acids or more, which are immunologically relevant as potential T-cell epitopes. Entropy-based analysis of the diversity of WNV sequences, revealed the presence of numerous evolutionarily stable nonamer positions across the proteome (entropy value of < or = 1). The representation (frequency) of nonamers variant to the predominant peptide at these stable positions was, generally, low (< or = 10% of the WNV sequences analyzed). Eighty-eight fragments of length 9-29 amino acids, representing approximately 34% of the WNV polyprotein length, were identified to be identical and evolutionarily stable in all analyzed WNV sequences. Of the 88 completely conserved sequences, 67 are also present in other flaviviruses, and several have been associated with the functional and structural properties of viral proteins. Immunoinformatic analysis revealed that the majority (78/88) of conserved sequences are potentially immunogenic, while 44 contained experimentally confirmed human T-cell epitopes. This study identified a comprehensive catalogue of completely conserved WNV sequences, many of which are shared by other flaviviruses, and majority are potential epitopes. The complete conservation of these immunologically relevant sequences through the entire recorded WNV history suggests they will be valuable as components of peptide-specific vaccines or other therapeutic applications, for sequence-specific diagnosis of a wide-range of Flavivirus infections, and for studies of homologous sequences among other flaviviruses.
Topics: Amino Acid Sequence; Animals; Antigens, Viral; Conserved Sequence; Databases, Protein; Epitopes, T-Lymphocyte; Evolution, Molecular; Genetic Variation; HLA Antigens; Humans; Molecular Sequence Data; Proteome; Viral Proteins; West Nile virus
PubMed: 19401763
DOI: 10.1371/journal.pone.0005352 -
Parasites & Vectors Sep 2016West Nile virus (WNV) represents a serious burden to human and animal health because of its capacity to cause unforeseen and large epidemics. Until 2004, only lineage 1... (Review)
Review
West Nile virus (WNV) represents a serious burden to human and animal health because of its capacity to cause unforeseen and large epidemics. Until 2004, only lineage 1 and 3 WNV strains had been found in Europe. Lineage 2 strains were initially isolated in 2004 (Hungary) and in 2008 (Austria) and for the first time caused a major WNV epidemic in 2010 in Greece with 262 clinical human cases and 35 fatalities. Since then, WNV lineage 2 outbreaks have been reported in several European countries including Italy, Serbia and Greece. Understanding the interaction of ecological factors that affect WNV transmission is crucial for preventing or decreasing the impact of future epidemics. The synchronous co-occurrence of competent mosquito vectors, virus, bird reservoir hosts, and susceptible humans is necessary for the initiation and propagation of an epidemic. Weather is the key abiotic factor influencing the life-cycles of the mosquito vector, the virus, the reservoir hosts and the interactions between them. The purpose of this paper is to review and compare mosquito population dynamics, and weather conditions, in three ecologically different contexts (urban/semi-urban, rural/agricultural, natural) across four European countries (Italy, France, Serbia, Greece) with a history of WNV outbreaks. Local control strategies will be described as well. Improving our understanding of WNV ecology is a prerequisite step for appraising and optimizing vector control strategies in Europe with the ultimate goal to minimize the probability of WNV infection.
Topics: Animals; Culicidae; Ecology; Europe; Humans; Mosquito Vectors; West Nile Fever; West Nile virus
PubMed: 27590848
DOI: 10.1186/s13071-016-1736-6 -
Science (New York, N.Y.) Oct 2011Many invasive species that have been spread through the globalization of trade and travel are pathogens. A paradigmatic case is the introduction of West Nile virus (WNV)... (Review)
Review
Many invasive species that have been spread through the globalization of trade and travel are pathogens. A paradigmatic case is the introduction of West Nile virus (WNV) into North America in 1999. A decade of research on the ecology and evolution of WNV includes three findings that provide insight into the outcome of future pathogen introductions. First, WNV transmission in North America is highest in urbanized and agricultural habitats, in part because the hosts and vectors of WNV are abundant in human-modified areas. Second, after its introduction, the virus quickly adapted to infect local mosquito vectors more efficiently than the originally introduced strain. Third, highly focused feeding patterns of the mosquito vectors of WNV result in unexpected host species being important for transmission. This research provides a framework for predicting and preventing the emergence of foreign vector-borne pathogens.
Topics: Agriculture; Animals; Biological Evolution; Bird Diseases; Birds; Culex; Ecosystem; Epidemics; Feeding Behavior; Humans; Insect Vectors; Internationality; Introduced Species; North America; Urbanization; West Nile Fever; West Nile virus
PubMed: 22021850
DOI: 10.1126/science.1201010 -
Viruses Apr 2024West Nile Virus (WNV) and Usutu Virus (USUV) are both neurotropic mosquito-borne viruses belonging to the family. These closely related viruses mainly follow an... (Review)
Review
West Nile Virus (WNV) and Usutu Virus (USUV) are both neurotropic mosquito-borne viruses belonging to the family. These closely related viruses mainly follow an enzootic cycle involving mosquitoes as vectors and birds as amplifying hosts, but humans and other mammals can also be infected through mosquito bites. WNV was first identified in Uganda in 1937 and has since spread globally, notably in Europe, causing periodic outbreaks associated with severe cases of neuroinvasive diseases such as meningitis and encephalitis. USUV was initially isolated in 1959 in Swaziland and has also spread to Europe, primarily affecting birds and having a limited impact on human health. There has been a recent expansion of these viruses' geographic range in Europe, facilitated by factors such as climate change, leading to increased human exposure. While sharing similar biological traits, ecology, and epidemiology, there are significant distinctions in their pathogenicity and their impact on both human and animal health. While WNV has been more extensively studied and is a significant public health concern in many regions, USUV has recently been gaining attention due to its emergence in Europe and the diversity of its circulating lineages. Understanding the pathophysiology, ecology, and transmission dynamics of these viruses is important to the implementation of effective surveillance and control measures. This perspective provides a brief overview of the current situation of these two viruses in Europe and outlines the significant challenges that need to be addressed in the coming years.
Topics: Europe; West Nile virus; Animals; Humans; Flavivirus; Flavivirus Infections; West Nile Fever; Birds; Culicidae; Mosquito Vectors; Disease Outbreaks
PubMed: 38675940
DOI: 10.3390/v16040599 -
Viruses Dec 2013The outbreak of West Nile virus (WNV) in 1999 in the USA, and its continued spread throughout the Americas, parts of Europe, the Middle East and Africa, underscored the... (Review)
Review
The outbreak of West Nile virus (WNV) in 1999 in the USA, and its continued spread throughout the Americas, parts of Europe, the Middle East and Africa, underscored the need for WNV antiviral development. Here, we review the current status of WNV drug discovery. A number of approaches have been used to search for inhibitors of WNV, including viral infection-based screening, enzyme-based screening, structure-based virtual screening, structure-based rationale design, and antibody-based therapy. These efforts have yielded inhibitors of viral or cellular factors that are critical for viral replication. For small molecule inhibitors, no promising preclinical candidate has been developed; most of the inhibitors could not even be advanced to the stage of hit-to-lead optimization due to their poor drug-like properties. However, several inhibitors developed for related members of the family Flaviviridae, such as dengue virus and hepatitis C virus, exhibited cross-inhibition of WNV, suggesting the possibility to re-purpose these antivirals for WNV treatment. Most promisingly, therapeutic antibodies have shown excellent efficacy in mouse model; one of such antibodies has been advanced into clinical trial. The knowledge accumulated during the past fifteen years has provided better rationale for the ongoing WNV and other flavivirus antiviral development.
Topics: Antibodies, Viral; Antiviral Agents; Clinical Trials as Topic; Drug Discovery; Drug Evaluation, Preclinical; Drug Repositioning; Humans; West Nile virus
PubMed: 24300672
DOI: 10.3390/v5122977