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Journal of Neuroinflammation Sep 2023Flaviviruses are arthropod-borne RNA viruses found worldwide that, when introduced into the human body, cause diseases, including neuroinfections, that can lead to... (Review)
Review
Flaviviruses are arthropod-borne RNA viruses found worldwide that, when introduced into the human body, cause diseases, including neuroinfections, that can lead to serious metabolic consequences and even death. Some of the diseases caused by flaviviruses occur continuously in certain regions, while others occur intermittently or sporadically, causing epidemics. Some of the most common flaviviruses are West Nile virus, dengue virus, tick-borne encephalitis virus, Zika virus and Japanese encephalitis virus. Since all the above-mentioned viruses are capable of penetrating the blood-brain barrier through different mechanisms, their actions also affect the central nervous system (CNS). Like other viruses, flaviviruses, after entering the human body, contribute to redox imbalance and, consequently, to oxidative stress, which promotes inflammation in skin cells, in the blood and in CNS. This review focuses on discussing the effects of oxidative stress and inflammation resulting from pathogen invasion on the metabolic antiviral response of the host, and the ability of viruses to evade the consequences of metabolic changes or exploit them for increased replication and further progression of infection, which affects the development of sequelae and difficulties in therapy.
Topics: Humans; Flavivirus; West Nile virus; Encephalitis Virus, Japanese; Zika Virus; Encephalitis Viruses, Tick-Borne; Inflammation; Central Nervous System Infections; Zika Virus Infection
PubMed: 37775774
DOI: 10.1186/s12974-023-02898-4 -
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 -
Viruses Sep 2013West Nile virus, genus Flavivirus, is transmitted between birds and occasionally other animals by ornithophilic mosquitoes. This virus also infects humans causing... (Review)
Review
West Nile virus, genus Flavivirus, is transmitted between birds and occasionally other animals by ornithophilic mosquitoes. This virus also infects humans causing asymptomatic infections in about 85% of cases and <1% of clinical cases progress to severe neuroinvasive disease. The virus also presents a threat since most infections remain unapparent. However, the virus contained in blood and organs from asymptomatically infected donors can be transmitted to recipients of these infectious tissues. This paper reviews the presently available methods to achieve the laboratory diagnosis of West Nile virus infections in humans, discussing the most prominent advantages and disadvantages of each in light of the results obtained during four different External Quality Assessment studies carried out by the European Network for 'Imported' Viral Diseases (ENIVD).
Topics: Clinical Laboratory Techniques; Diagnostic Tests, Routine; Humans; Quality Assurance, Health Care; West Nile Fever; West Nile virus
PubMed: 24072061
DOI: 10.3390/v5102329 -
International Journal of Environmental... Dec 2013In this review, we discuss the possibility that the glycosylation of West Nile (WN) virus E-protein may be associated with enhanced pathogenicity and higher replication... (Review)
Review
In this review, we discuss the possibility that the glycosylation of West Nile (WN) virus E-protein may be associated with enhanced pathogenicity and higher replication of WN virus. The results indicate that E-protein glycosylation allows the virus to multiply in a heat-stable manner and therefore, has a critical role in enhanced viremic levels and virulence of WN virus in young-chick infection model. The effect of the glycosylation of the E protein on the pathogenicity of WN virus in young chicks was further investigated. The results indicate that glycosylation of the WN virus E protein is important for viral multiplication in peripheral organs and that it is associated with the strong pathogenicity of WN virus in birds. The micro-focus reduction neutralization test (FRNT) in which a large number of serum samples can be handled at once with a small volume (15 μL) of serum was useful for differential diagnosis between Japanese encephalitis and WN virus infections in infected chicks. Serological investigation was performed among wild birds in the Far Eastern region of Russia using the FRNT. Antibodies specific to WN virus were detected in 21 samples of resident and migratory birds out of 145 wild bird samples in the region.
Topics: Animals; Bird Diseases; Birds; Glycosylation; Seroepidemiologic Studies; Siberia; Viral Envelope Proteins; West Nile Fever; West Nile virus
PubMed: 24351738
DOI: 10.3390/ijerph10127144 -
Viruses Oct 2013CD4 and CD8 T lymphocytes are adaptive immune cells that play a key role in the immune response to pathogens. They have been extensively studied in a variety of model... (Review)
Review
CD4 and CD8 T lymphocytes are adaptive immune cells that play a key role in the immune response to pathogens. They have been extensively studied in a variety of model systems and the mechanisms by which they function are well described. However, the responses by these cell types vary widely from pathogen to pathogen. In this review, we will discuss the role of CD8 and CD4 T cells in the immune response to West Nile virus infection.
Topics: Animals; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Humans; West Nile Fever; West Nile virus
PubMed: 24153060
DOI: 10.3390/v5102573 -
Viruses Mar 2023West Nile virus (WNV) is a mosquito-borne pathogen that can lead to encephalitis and death in susceptible hosts. Cytokines play a critical role in inflammation and... (Review)
Review
West Nile virus (WNV) is a mosquito-borne pathogen that can lead to encephalitis and death in susceptible hosts. Cytokines play a critical role in inflammation and immunity in response to WNV infection. Murine models provide evidence that some cytokines offer protection against acute WNV infection and assist with viral clearance, while others play a multifaceted role WNV neuropathogenesis and immune-mediated tissue damage. This article aims to provide an up-to-date review of cytokine expression patterns in human and experimental animal models of WNV infections. Here, we outline the interleukins, chemokines, and tumor necrosis factor superfamily ligands associated with WNV infection and pathogenesis and describe the complex roles they play in mediating both protection and pathology of the central nervous system during or after virus clearance. By understanding of the role of these cytokines during WNV neuroinvasive infection, we can develop treatment options aimed at modulating these immune molecules in order to reduce neuroinflammation and improve patient outcomes.
Topics: Humans; Mice; Animals; West Nile Fever; Tumor Necrosis Factors; West Nile virus; Cytokines; Chemokines; Interleukins
PubMed: 36992514
DOI: 10.3390/v15030806 -
International Journal of Molecular... Apr 2019West Nile virus (WNV) is an arbovirus with important public health implications globally. This study characterizes a viral isolate, 2004Hou3, in comparison with the NY99...
West Nile virus (WNV) is an arbovirus with important public health implications globally. This study characterizes a viral isolate, 2004Hou3, in comparison with the NY99 strain from the original WNV outbreak in New York, USA. NextGen sequencing was used to compare the viral isolates genetically, while wild-type C57/BL6 mice were used to compare pathogenicity and viral persistence. Significant differences in survival and clinical presentations were noted, with minor genetic variations between the two strains potentially offering an explanation. One notable difference is that 5 of 35 mice infected with the 2004Hou3 strain developed hind limb flaccid paralysis, suggesting its possible use as a small animal pathogenesis model for this clinical characteristic often observed in human WN neuroinvasive disease patients but not reported in other animal models of infection. Overall, this study suggests that 2004Hou3 is a less pathogenic strain with potential for use in long-term outcome studies using small animal models.
Topics: Animals; Body Fluids; Chlorocebus aethiops; Female; Genotype; Mice, Inbred C57BL; Phenotype; Sequence Analysis, DNA; Survival Analysis; Vero Cells; West Nile Fever; West Nile virus
PubMed: 31010172
DOI: 10.3390/ijms20081936 -
PLoS Pathogens Nov 2011In nature, arthropod-borne viruses (arboviruses) perpetuate through alternating replication in vertebrate and invertebrate hosts. The trade-off hypothesis proposes that...
In nature, arthropod-borne viruses (arboviruses) perpetuate through alternating replication in vertebrate and invertebrate hosts. The trade-off hypothesis proposes that these viruses maintain adequate replicative fitness in two disparate hosts in exchange for superior fitness in one host. Releasing the virus from the constraints of a two-host cycle should thus facilitate adaptation to a single host. This theory has been addressed in a variety of systems, but remains poorly understood. We sought to determine the fitness implications of alternating host replication for West Nile virus (WNV) using an in vivo model system. Previously, WNV was serially or alternately passed 20 times in vivo in chicks or mosquitoes and resulting viruses were characterized genetically. In this study, these test viruses were competed in vivo in fitness assays against an unpassed marked reference virus. Fitness was assayed in chicks and in two important WNV vectors, Culex pipiens and Culex quinquefasciatus. Chick-specialized virus displayed clear fitness gains in chicks and in Cx. pipiens but not in Cx. quinquefasciatus. Cx. pipiens-specialized virus experienced reduced fitness in chicks and little change in either mosquito species. These data suggest that when fitness is measured in birds the trade-off hypothesis is supported; but in mosquitoes it is not. Overall, these results suggest that WNV evolution is driven by alternate cycles of genetic expansion in mosquitoes, where purifying selection is weak and genetic diversity generated, and restriction in birds, where purifying selection is strong.
Topics: Animals; Biological Evolution; Chickens; Culex; Genetic Fitness; Genetic Variation; Host-Pathogen Interactions; Selection, Genetic; Serial Passage; West Nile Fever; West Nile virus
PubMed: 22102808
DOI: 10.1371/journal.ppat.1002335 -
PLoS Neglected Tropical Diseases Nov 2017The West Nile virus (WNV), isolated in 1937, is an arbovirus (arthropod-borne virus) that infects thousands of people each year. Despite its burden on global health,...
The West Nile virus (WNV), isolated in 1937, is an arbovirus (arthropod-borne virus) that infects thousands of people each year. Despite its burden on global health, little is known about the virus' biological and evolutionary dynamics. As several lineages are endemic in West Africa, we obtained the complete polyprotein sequence from three isolates from the early 1990s, each representing a different lineage. We then investigated differences in growth behavior and pathogenicity for four distinct West African lineages in arthropod (Ap61) and primate (Vero) cell lines, and in mice. We found that genetic differences, as well as viral-host interactions, could play a role in the biological properties in different WNV isolates in vitro, such as: (i) genome replication, (ii) protein translation, (iii) particle release, and (iv) virulence. Our findings demonstrate the endemic diversity of West African WNV strains and support future investigations into (i) the nature of WNV emergence, (ii) neurological tropism, and (iii) host adaptation.
Topics: Africa, Western; Animals; Arthropods; Biological Variation, Population; Cell Line; Genetic Variation; Host-Pathogen Interactions; Mice; Phylogeny; Polyproteins; Primates; Sequence Analysis, DNA; Viral Proteins; Virulence; Virus Replication; West Nile virus
PubMed: 29117195
DOI: 10.1371/journal.pntd.0006078 -
Antiviral Chemistry & Chemotherapy May 2011Dengue fever, dengue haemorrhagic fever, and dengue shock syndrome are caused by infections with any of the four serotypes of the dengue virus (DENV), and are an...
BACKGROUND
Dengue fever, dengue haemorrhagic fever, and dengue shock syndrome are caused by infections with any of the four serotypes of the dengue virus (DENV), and are an increasing global health risk. The related West Nile virus (WNV) causes significant morbidity and mortality as well, and continues to be a threat in endemic areas. Currently no FDA-approved vaccines or therapeutics are available to prevent or treat any of these infections. Like the other members of Flaviviridae, DENV and WNV encode a protease (NS3) which is essential for viral replication and therefore is a promising target for developing therapies to treat dengue and West Nile infections.
METHODS
Flaviviral protease inhibitors were identified and biologically characterized for mechanism of inhibition and DENV antiviral activity.
RESULTS
A guanidinylated 2,5-dideoxystreptamine class of compounds was identified that competitively inhibited the NS3 protease from DENV(1-4) and WNV with 50% inhibitory concentration values in the 1-70 μM range. Cytotoxicity was low; however, antiviral activity versus DENV-2 on VERO cells was not detectable.
CONCLUSIONS
This class of compounds is the first to demonstrate competitive pan-dengue and WNV NS3 protease inhibition and, given the sequence conservation among flavivirus NS3 proteins, suggests that developing a pan-dengue or possibly pan-flavivirus therapeutic is feasible.
Topics: Animals; Antiviral Agents; Chlorocebus aethiops; Dengue Virus; Microbial Sensitivity Tests; Molecular Structure; Molecular Weight; Protease Inhibitors; RNA Helicases; Serine Endopeptidases; Structure-Activity Relationship; Vero Cells; Viral Nonstructural Proteins; West Nile virus
PubMed: 21566267
DOI: 10.3851/IMP1767