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Pathogens (Basel, Switzerland) May 2024West Nile virus (WNV) neuroinvasive disease (WNND) occurs in approximately 1 percent of WNV-infected patients and typically presents as encephalitis, meningitis, or...
West Nile virus (WNV) neuroinvasive disease (WNND) occurs in approximately 1 percent of WNV-infected patients and typically presents as encephalitis, meningitis, or acute flaccid paralysis (AFP). WNND remains a difficult inpatient diagnosis, creating significant challenges for prognostication and therapy selection. We characterized the clinical and diagnostic features of WNND cases at two major academic medical centers in New York City in routine clinical practice. We retrospectively reviewed the charts of thirty-six patients with WNND, including twenty-six encephalitis, four meningitis, and six AFP cases. The most common presenting symptoms were fever (86.1%) and gastrointestinal symptoms (38.9%) in addition to altered mental status (72.2%), lethargy (63.9%), gait disturbances (46.2%), and headache (44.4%). Fourteen (48.3%) patients displayed acute magnetic resonance imaging (MRI) findings, particularly T2 hyperintensities in the bilateral thalami, brainstem, and deep white matter. New York State Department of Health WNV CSF IgM testing was utilized for diagnosis in 58.3% of patients; however, just 38.1% had the result by discharge, compared to 85.6% of those who underwent serum IgM testing. The median length of stay was 13.5 days, 38.9% were intubated, and three patients (8.9%) died during acute hospitalization. Our findings underscore the morbidity, mortality, and diagnostic challenges of WNND, suggesting the potential utility of serum IgM testing in combination with confirmatory CSF testing to expedite diagnosis in the acute setting.
PubMed: 38787234
DOI: 10.3390/pathogens13050382 -
Veterinary Sciences May 2024The aim of this study was to analyze the seroprevalence of West Nile virus (WNV) among equids in Bulgaria, confirm the results of a competitive ELISA versus the virus...
The aim of this study was to analyze the seroprevalence of West Nile virus (WNV) among equids in Bulgaria, confirm the results of a competitive ELISA versus the virus neutralization test (VNT) and investigate some predisposing factors for WNV seropositivity. A total of 378 serum samples from 15 provinces in northern and southern Bulgaria were tested. The samples originated from 314 horses and 64 donkeys, 135 males and 243 females, aged from 1 to 30 years. IgG and IgM antibodies against WNV protein E were detected by ELISA. ELISA-positive samples were additionally tested via VNT for WNV and Usutu virus. Thirty-five samples were WNV-positive by ELISA (9.26% [CI = 6.45-12.88]), of which 15 were confirmed by VNT; hence, the seroprevalence was 3.97% (CI = 2.22-6.55). No virus-neutralizing antibodies to Usutu virus were detected among the 35 WNV-ELISA-positive equids in Bulgaria. When compared with VNT, ELISA showed 100.0% sensitivity and 94.5% specificity. A statistical analysis showed that the risk factors associated with WNV seropositivity were the region ( < 0.0001), altitude of the locality ( < 0.0001), type of housing ( < 0.0001) and breed ( = 0.0365). The results of the study demonstrate, albeit indirectly, that WNV circulates among equids in northern and southern Bulgaria, indicating that they could be suitable sentinel animals for predicting human cases and determining the risk in these areas or regions of the country.
PubMed: 38787181
DOI: 10.3390/vetsci11050209 -
Structure (London, England : 1993) May 2024Flaviviruses are single-stranded positive-sense RNA (+RNA) viruses that are responsible for several (re)emerging diseases such as yellow, dengue, or West Nile fevers....
Flaviviruses are single-stranded positive-sense RNA (+RNA) viruses that are responsible for several (re)emerging diseases such as yellow, dengue, or West Nile fevers. The Zika epidemic highlighted their dangerousness when a relatively benign virus known since the 1950s turned into a deadly pathogen. The central protein for their replication is NS5 (non-structural protein 5), which is composed of the N-terminal methyltransferase (MTase) domain and the C-terminal RNA-dependent RNA-polymerase (RdRp) domain. It is responsible for both RNA replication and installation of the 5' RNA cap. We structurally and biochemically analyzed the Ntaya virus MTase and RdRp domains and we compared their properties to other flaviviral NS5s. The enzymatic centers are well conserved across Flaviviridae, suggesting that the development of drugs targeting all flaviviruses is feasible. However, the enzymatic activities of the isolated proteins were significantly different for the MTase domains.
PubMed: 38781970
DOI: 10.1016/j.str.2024.04.020 -
Science Signaling May 2024Oligoadenylate synthetase 3 (OAS3) and ribonuclease L (RNase L) are components of a pathway that combats viral infection in mammals. Upon detection of viral...
Oligoadenylate synthetase 3 (OAS3) and ribonuclease L (RNase L) are components of a pathway that combats viral infection in mammals. Upon detection of viral double-stranded RNA (dsRNA), OAS3 synthesizes 2'-5'-oligo(A), which activates the RNase domain of RNase L by promoting the homodimerization and oligomerization of RNase L monomers. Activated RNase L rapidly degrades all cellular mRNAs, shutting off several cellular processes. We sought to understand the molecular mechanisms underlying the rapid activation of RNase L in response to viral infection. Through superresolution microscopy and live-cell imaging, we showed that OAS3 and RNase L concentrated into higher-order cytoplasmic complexes known as dsRNA-induced foci (dRIF) in response to dsRNA or infection with dengue virus, Zika virus, or West Nile virus. The concentration of OAS3 and RNase L at dRIF corresponded with the activation of RNase L-mediated RNA decay. We showed that dimerized/oligomerized RNase L concentrated in a liquid-like shell surrounding a core OAS3-dRIF structure and dynamically exchanged with the cytosol. These data establish that the condensation of dsRNA, OAS3, and RNase L into dRIF is a molecular switch that promotes the rapid activation of RNase L upon detection of dsRNA in mammalian cells.
Topics: Endoribonucleases; Humans; 2',5'-Oligoadenylate Synthetase; RNA, Double-Stranded; Zika Virus; Animals; Dengue Virus; RNA, Viral; RNA Stability; West Nile virus; Zika Virus Infection; Enzyme Activation; HeLa Cells; HEK293 Cells
PubMed: 38771918
DOI: 10.1126/scisignal.adi9844 -
PloS One 2024
PubMed: 38758813
DOI: 10.1371/journal.pone.0304217 -
Euro Surveillance : Bulletin Europeen... May 2024collected in 2023 in the greater Paris area (Île-de-France) were experimentally able to transmit five arboviruses: West Nile virus from 3 days post-infection (dpi),...
collected in 2023 in the greater Paris area (Île-de-France) were experimentally able to transmit five arboviruses: West Nile virus from 3 days post-infection (dpi), chikungunya virus and Usutu virus from 7 dpi, dengue virus and Zika virus from 21 dpi. Given the growing number of imported dengue cases reported in early 2024 in France, surveillance of should be reinforced during the Paris Olympic Games in July, when many international visitors including from endemic countries are expected.
Topics: Animals; Aedes; Humans; Zika Virus; Dengue Virus; Chikungunya virus; Paris; Mosquito Vectors; West Nile virus; Arboviruses; Arbovirus Infections; Flavivirus; France; Dengue; Zika Virus Infection
PubMed: 38757289
DOI: 10.2807/1560-7917.ES.2024.29.20.2400271 -
Survey of Ophthalmology May 2024A 51-year-old man presented with decreased vision, fever, confusion, headaches, agitation, nausea, vomiting and diarrhea. Magnetic resonance imaging of the brain...
A 51-year-old man presented with decreased vision, fever, confusion, headaches, agitation, nausea, vomiting and diarrhea. Magnetic resonance imaging of the brain demonstrated bilateral T2 hyperintense lesions in the region of the mesial temporal lobe and optic radiations. There was a predominantly polymorphonuclear leukocyte pleocytosis in the cerebrospinal fluid (CSF) with hyperproteinorachia. A meningoencephalitis was diagnosed. Intravenous fluorescein angiography (IVFA) demonstrated a multifocal chorioretinitis that was in a linear pattern in the left eye. CSF enzyme-linked immunosorbent assay was positive for West Nile virus (WNV) IgM. We review the clinical manifestations of WNV disease and highlight the value of IVFA in determining the diagnosis.
PubMed: 38750826
DOI: 10.1016/j.survophthal.2024.05.003 -
Journal of Alzheimer's Disease Reports 2024In comparison to persons who did not have viral encephalitis, people with viral encephalitis had a later-life risk of Alzheimer's disease (AD) that was 31 times higher....
BACKGROUND
In comparison to persons who did not have viral encephalitis, people with viral encephalitis had a later-life risk of Alzheimer's disease (AD) that was 31 times higher. In a previous study, we were able to confirm the association of viral encephalitis with AD and suggest that West Nile Virus infection is a significant AD risk factor. A genome wide association study (GWAS) with UK Biobank data revealed that the gene RAR Related Orphan Receptor B (RORB) is significantly associated with viral encephalitis.
OBJECTIVE
To use data from the 8 PheWeb datasets to try to identify genes other than RORB that might be involved in both infectious encephalitis and AD.
METHODS
PheWeb includes data from UKBB and 5 other databanks. We used UK Biobank data to examine gene expression and phenotypic expression.
RESULTS
PheWeb identified additional genes associated with both infectious encephalitis and AD. RPTOR, a gene associated with the mTOR pathway, emerges as significant. Analyses of UK Biobank data reveal the impact of RPTOR on AD risk, with carriers of the minor allele A exhibiting decreased prevalence in subjects under age 55. Further analysis demonstrates that RPTOR genotypes influence body mass index (BMI) in subjects of all ages, with carriers of the minor allele A having lower BMI. Logistic regression analyses confirm the association between reduced BMI and increased AD risk, along with the established factor of age.
CONCLUSIONS
RPTOR may represent an AD gene, though mTOR's role in AD and BMI is complex. Nevertheless, RPTOR and mTOR could represent potential therapeutic targets for AD.
PubMed: 38746632
DOI: 10.3233/ADR-230185 -
MSystems Jun 2024In arthropod-associated microbial communities, insect-specific viruses (ISVs) are prevalent yet understudied due to limited infectivity outside their natural hosts....
In arthropod-associated microbial communities, insect-specific viruses (ISVs) are prevalent yet understudied due to limited infectivity outside their natural hosts. However, ISVs might play a crucial role in regulating mosquito populations and influencing arthropod-borne virus transmission. Some studies have indicated a core virome in mosquitoes consisting of mostly ISVs. Employing single mosquito metagenomics, we comprehensively profiled the virome of native and invasive mosquito species in Belgium. This approach allowed for accurate host species determination, prevalence assessment of viruses and , and the identification of novel viruses. Contrary to our expectations, no abundant core virome was observed in mosquitoes from Belgium. In that regard, we caution against rigidly defining mosquito core viromes and encourage nuanced interpretations of other studies. Nonetheless, our study identified 45 viruses of which 28 were novel, enriching our understanding of the mosquito virome and ISVs. We showed that the mosquito virome in this study is species-specific and less dependent on the location where mosquitoes from the same species reside. In addition, because has previously been observed to influence arbovirus transmission, we report the prevalence of in Belgian mosquitoes and the detection of several mobile genetic elements. The observed prevalence ranged from 83% to 92% in members from the complex.IMPORTANCE mosquitoes are important vectors for arboviruses like West Nile virus and Usutu virus. Virome studies on individual , and on individual mosquitoes in general, have been lacking. To mitigate this, we sequenced the virome of 190 individual and 8 individual mosquitoes. We report the lack of a core virome in these mosquitoes from Belgium and caution the interpretation of other studies in this light. The discovery of new viruses in this study will aid our comprehension of insect-specific viruses and the mosquito virome in general in relation to mosquito physiology and mosquito population dynamics.
Topics: Animals; Culex; Virome; Wolbachia; Belgium; Species Specificity; Mosquito Vectors; Metagenomics; Insect Viruses; Climate
PubMed: 38742876
DOI: 10.1128/msystems.00012-24 -
IScience Apr 2024Rab27a, a Rab family small GTPases, plays an important role in the trafficking and secretion of the intracellular proteins and has been reported to promote various viral...
Rab27a, a Rab family small GTPases, plays an important role in the trafficking and secretion of the intracellular proteins and has been reported to promote various viral multiplication. However, whether Rab27a is involved in West Nile virus (WNV) multiplication is unknown. This study examined the ability of Rab27a to suppress WNV multiplication. The inhibition of Rab27a expression increased viral multiplication and the intracellular levels of WNV structural proteins, E and prM proteins. Rab27a partially colocalized with E protein, mainly in the perinuclear region, while inhibition of Rab27a expression resulted in diffuse subcellular localization of E protein. In addition, some of the perinuclear E protein colocalized with the lysosomal marker LAMP1, and inhibition of lysosomal acidification increased intracellular levels of Rab27a and E proteins. These observations suggested that Rab27a inhibits WNV multiplication by inducing the degradation of viral protein in lysosomes.
PubMed: 38715944
DOI: 10.1016/j.isci.2024.109539