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Usutu Virus, West Nile Virus and Neglected Flaviviruses

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A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Human Virology and Viral Diseases".

Deadline for manuscript submissions: closed (30 June 2024) | Viewed by 15342

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Prof. Dr. Yannick Simonin

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Institut de Génétique Moléculaire de Montpellier, University of Montpellier. Pathogenesis and Control of Chronic and Emerging Infections (PCCEI), 60 Rue de Navacelles, 34394 Montpellier, CEDEX 5, France
Interests: pathogenesis and diagnosis of emerging viruses especially flaviviruses and neurotropic viruses
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Dr. Daniel Cadar

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Bernhard Nocht Institut fur Tropenmedizin Hamburgdisabled, Hamburg, Germany
Interests: virus metagenomics; novel viruses; arboviruses; phylogeography; virus ecology and evolution
Special Issues, Collections and Topics in MDPI journals

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Dear Colleagues,

In the last decade, the number of emerging Flaviviruses described worldwide has increased considerably. Among them, the recent expansion of emerging neurotropic arthropod-borne viruses, such as West Nile virus (WNV), Usutu virus (USUV) or tickborne encephalitis virus (TBEV), or neglected flaviviruses, such as Powassan virus (POWV), over their natural range of distribution deserves special attention. Expansion and endemicity increase the spatial and temporal overlap of flaviviruses, posing significant challenges for surveillance and control.

In this Special Issue, we invite colleagues to submit their original research articles and scientific reviews to assemble a collection of papers highlighting the critical advancements in our understanding of the above-mentioned flaviviruses including the neglected flaviviruses on all aspects of viral infection including (but not restricted to) cellular, molecular and immunological aspects of infection, cell–virus interactions, factors responsible for virus virulence, epidemiology, transmission, vector competence and diagnosis.

Prof. Dr. Yannick Simonin
Dr. Daniel Cadar
Guest Editors

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Keywords

USUV
WNV
TBEV
neglected flaviviruses
arboviruses
epidemiology
pathogenesis
cell-virus interaction

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Published Papers (9 papers)

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16 pages, 2131 KiB

Open AccessArticle

Transcriptional Response to Tick-Borne Flavivirus Infection in Neurons, Astrocytes and Microglia In Vivo and In Vitro

by Ebba Rosendal, Richard Lindqvist, Nunya Chotiwan, Johan Henriksson and Anna K. Överby

Viruses 2024, 16(8), 1327; https://doi.org/10.3390/v16081327 - 19 Aug 2024

Viewed by 1196

Abstract

Tick-borne encephalitis virus (TBEV) is a neurotropic member of the genus Orthoflavivirus (former Flavivirus) and is of significant health concern in Europe and Asia. TBEV pathogenesis may occur directly via virus-induced damage to neurons or through immunopathology due to excessive inflammation. While primary cells isolated from the host can be used to study the immune response to TBEV, it is still unclear how well these reflect the immune response elicited in vivo. Here, we compared the transcriptional response to TBEV and the less pathogenic tick-borne flavivirus, Langat virus (LGTV), in primary monocultures of neurons, astrocytes and microglia in vitro, with the transcriptional response in vivo captured by single-nuclei RNA sequencing (snRNA-seq) of a whole mouse cortex. We detected similar transcriptional changes induced by both LGTV and TBEV infection in vitro, with the lower response to LGTV likely resulting from slower viral kinetics. Gene set enrichment analysis showed a stronger transcriptional response in vivo than in vitro for astrocytes and microglia, with a limited overlap mainly dominated by interferon signaling. Together, this adds to our understanding of neurotropic flavivirus pathogenesis and the strengths and limitations of available model systems. Full article

(This article belongs to the Special Issue Usutu Virus, West Nile Virus and Neglected Flaviviruses)

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15 pages, 7798 KiB

Open AccessArticle

Cross-Reactive Antibodies to the NS1 Protein of Omsk Hemorrhagic Fever Virus Are Absent in the Sera of Patients with Tick-Borne Encephalitis

by Bogdana I. Kravchuk, Yana A. Khlusevich, Galina S. Chicherina, Valeriy V. Yakimenko, Elena I. Krasnova, Nina N. Tikunova and Andrey L. Matveev

Viruses 2024, 16(7), 1032; https://doi.org/10.3390/v16071032 - 27 Jun 2024

Cited by 1 | Viewed by 1072

Abstract

Omsk hemorrhagic fever virus (OHFV) is a member of the tick-borne encephalitis virus (TBEV) complex of the Flaviviridae family. Currently, there are no data on the cross-reactivity of antibodies to the NS1 proteins of OHFV and TBEV. Such data are of major interest for monitoring viral encephalitis of unknown etiology due to the increasing geographical distribution of OHFV. In this study, a recombinant OHFV NS1 protein was produced using the Escherichia coli expression system and purified. The recombinant OHFV NS1 protein was recognized by specific mice immune ascetic fluids to the native OHFV NS1 protein. A Western blot analysis and ELISA of the recombinant NS1 proteins of OHFV and TBEV were used to study the cross-reactivity of antibodies from immune ascites fluid obtained from OHFV-infected mice and mAbs against TBEV NS1. Anti-TBEV NS1 mouse monoclonal antibodies (mAbs) have been shown to not be cross-reactive to the OHFV NS1 protein. Sera from patients with confirmed tick-borne encephalitis (TBE) were examined by ELISA using recombinant OHFV NS1 and TBEV NS1 proteins as antigens. It was shown for the first time that cross-reactive antibodies to the OHFV NS1 protein were not detected in the sera of TBE patients, whereas the sera contained antibodies to the TBEV NS1 protein. Full article

(This article belongs to the Special Issue Usutu Virus, West Nile Virus and Neglected Flaviviruses)

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17 pages, 3416 KiB

Open AccessArticle

Evaluation of Non-Vector Transmission of Usutu Virus in Domestic Canaries (Serinus canaria)

by Aude Blanquer, Felipe Rivas, Mazarine Gérardy, Michaël Sarlet, Nassim Moula, Ute Ziegler, Martin H. Groschup, Daniel Desmecht, Thomas Marichal and Mutien Garigliany

Viruses 2024, 16(1), 79; https://doi.org/10.3390/v16010079 - 3 Jan 2024

Cited by 1 | Viewed by 1488

Abstract

Usutu virus (USUV) is a flavivirus transmitted to avian species through mosquito bites that causes mass mortalities in wild and captive bird populations. However, several cases of positive dead birds have been recorded during the winter, a vector-free period. To explain how USUV “overwinters”, the main hypothesis is bird-to-bird transmission, as shown for the closely related West Nile virus. To address this question, we experimentally challenged canaries with intranasal inoculation of USUV, which led to systemic dissemination of the virus, provided the inoculated dose was sufficient (>10² TCID₅₀). We also highlighted the oronasal excretion of infectious viral particles in infected birds. Next, we co-housed infected birds with naive sentinels, to determine whether onward transmission could be reproduced experimentally. We failed to detect such transmission but demonstrated horizontal transmission by transferring sputum from an infected to a naive canary. In addition, we evaluated the cellular tropism of respiratory mucosa to USUV in vitro using a canary tracheal explant and observed only limited evidence of viral replication. Further research is then needed to assess if and how comparable bird-to-bird transmission occurs in the wild. Full article

(This article belongs to the Special Issue Usutu Virus, West Nile Virus and Neglected Flaviviruses)

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11 pages, 1694 KiB

Open AccessArticle

Serologic and Genomic Investigation of West Nile Virus in Kosovo

by Petra Emmerich, Xhevat Jakupi, Kurtesh Sherifi, Shemsedin Dreshaj, Ariana Kalaveshi, Christoph Hemmer, Donjeta Pllana Hajdari, Ronald von Possel, Dániel Cadar and Alexandru Tomazatos

Viruses 2024, 16(1), 66; https://doi.org/10.3390/v16010066 - 30 Dec 2023

Viewed by 1586

Abstract

The prevalence of West Nile virus (WNV) is increasing across Europe, with cases emerging in previously unaffected countries. Kosovo is situated in a WNV-endemic region where the seroepidemiological data on WNV in humans remains absent. To address this issue, we have conducted a seroepidemiological investigation of 453 randomly selected sera from a hospital in Kosovo, revealing a 1.55% anti-WNV IgG seroprevalence. Comparative and phylogeographic analyses of the WNV genomes obtained by sequencing archived samples from patients with West Nile fever indicate at least two recent and distinct introductions of WNV lineage 2 into Kosovo from neighboring countries. These findings confirm the eco-epidemiological status of WNV in southeast Europe, where long- and short-range dispersion of lineage 2 strains contributes to a wider circulation via central Europe. Our results suggest an increasing risk for WNV spreading in Kosovo, underscoring the need for an integrated national surveillance program targeting vectors and avian populations for early epidemic detection, as well as the screening of blood donors to gauge the impact of virus circulation on the human population. Full article

(This article belongs to the Special Issue Usutu Virus, West Nile Virus and Neglected Flaviviruses)

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8 pages, 999 KiB

Open AccessCommunication

Re-Emergence of a West Nile Virus (WNV) Variant in South Spain with Rapid Spread Capacity

by María José Ruiz-López, Pilar Aguilera-Sepúlveda, Sonia Cebrián-Camisón, Jordi Figuerola, Sergio Magallanes, Sarai Varona, Isabel Cuesta, Cristina Cano-Gómez, Patricia Sánchez-Mora, Juan Camacho, Carolina Sánchez-Peña, Francisco José Marchena, Ulises Ameyugo, Santiago Ruíz, María Paz Sánchez-Seco, Montserrat Agüero, Miguel Ángel Jiménez-Clavero, Jovita Fernández-Pinero and Ana Vázquez

Viruses 2023, 15(12), 2372; https://doi.org/10.3390/v15122372 - 1 Dec 2023

Cited by 4 | Viewed by 2559

Abstract

West Nile Virus (WNV) is a mosquito vector-borne zoonosis with an increasing incidence in Europe that has become a public health concern. In Spain, although local circulation has been known for decades, until 2020, when a large outbreak occurred, West Nile Virus cases were scarce and mostly occurred in southern Spain. Since then, there have been new cases every year and the pathogen has spread to new regions. Thus, monitoring of circulating variants and lineages plays a fundamental role in understanding WNV evolution, spread and dynamics. In this study, we sequenced WNV consensus genomes from mosquito pools captured in 2022 as part of a newly implemented surveillance program in southern Spain and compared it to other European, African and Spanish sequences. Characterization of WNV genomes in mosquitoes captured in 2022 reveals the co-circulation of two WNV lineage 1 variants, the one that caused the outbreak in 2020 and another variant that is closely related to variants reported in Spain in 2012, France in 2015, Italy in 2021–2022 and Senegal in 2012–2018. The geographic distribution of these variants indicates that WNV L1 dynamics in southern Europe include an alternating dominance of variants in some territories. Full article

(This article belongs to the Special Issue Usutu Virus, West Nile Virus and Neglected Flaviviruses)

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12 pages, 1164 KiB

Open AccessArticle

The Prevalence, Seroprevalence, and Risk Factors of Tick-Borne Encephalitis Virus in Dogs in Lithuania, a Highly Endemic State

by Evelina Simkute, Arnoldas Pautienius, Juozas Grigas, Paulina Urbute and Arunas Stankevicius

Viruses 2023, 15(11), 2265; https://doi.org/10.3390/v15112265 - 17 Nov 2023

Cited by 1 | Viewed by 1645

Abstract

The rising awareness and increasing number of case reports of tick-borne encephalitis (TBE) in dogs indicate that the virus might be an important tick-borne pathogen in dogs, especially in endemic areas. Therefore, the aim of the present study was to investigate the prevalence rate of TBEV RNA and TBEV-specific antibodies in clinical samples of dogs living in a highly endemic region of Lithuania and to evaluate the main risk factors for severe disease course and death. The blood samples (n = 473) of dogs were collected in two veterinary clinics in central Lithuania. Tick-borne encephalitis virus (TBEV) RNA was detected in 18.6% (88/473; CI 95% 15.2–22.4) and TBEV-specific antibodies were found in 21.6% (102/473; CI 95% 17.9–25.6) of dog blood serum samples after confirmation with a virus neutralization test. The death/euthanasia rate was 18.2% (16/88; CI 95% 10.8–27.8) in PCR-positive dogs. Male dogs were more likely to develop neurological symptoms (p = 0.008). Older dogs (p = 0.003), dogs with the presence of neurological symptoms (p = 0.003), and dogs with the presence of TBEV-specific antibodies (p = 0.024) were more likely to experience worse outcomes of the disease. The results of the present study demonstrate that TBEV is a common and clinically important pathogen in dogs in such endemic countries as Lithuania. Full article

(This article belongs to the Special Issue Usutu Virus, West Nile Virus and Neglected Flaviviruses)

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12 pages, 1427 KiB

Open AccessArticle

High Seroprevalence of IgG Antibodies to Multiple Arboviruses in People Living with HIV (PLWHIV) in Madagascar

by Fetra Angelot Rakotomalala, Julie Bouillin, Santatriniaina Dauphin Randriarimanana, Guillaume Thaurignac, Luca Maharavo, Mihaja Raberahona, Lucien Razafindrakoto, Jasmina Rasoanarivo, Mala Rakoto-Andrianarivelo, Danielle Aurore Doll Rakoto, François Xavier Babin, Tahinamandranto Rasamoelina, Eric Delaporte, Luc Hervé Samison, Martine Peeters, Eric Nerrienet and Ahidjo Ayouba

Viruses 2023, 15(11), 2258; https://doi.org/10.3390/v15112258 - 15 Nov 2023

Cited by 3 | Viewed by 1703

Abstract

To estimate the prevalence of IgG antibodies against six arboviruses in people living with HIV-1 (PLWHIV) in Madagascar, we tested samples collected between January 2018 and June 2021. We used a Luminex-based serological assay to detect IgG antibodies against antigens from Dengue virus serotypes 1–4 (DENV1–4), Zika virus (ZIKV), West Nile virus (WNV), Usutu virus (USUV), Chikungunya virus (CHIKV), and O’nyong nyong virus (ONNV). Of the 1036 samples tested, IgG antibody prevalence was highest for ONNV (28.4%), CHIKV (26.7%), WNV-NS1 (27.1%), DENV1 (12.4%), USUV (9.9%), and DENV3 (8.9%). ZIKV (4.9%), DENV2 (4.6%), WNV-D3 (5.1%), and DENV4 (1.4%) were lower. These rates varied by province of origin, with the highest rates observed in Toamasina, on the eastern coast (50.5% and 56.8%, for CHIKV and ONNV, respectively). The seroprevalence increased with age for DENV1 and 3 (p = 0.006 and 0.038, respectively) and WNV DIII (p = 0.041). The prevalence of IgG antibodies against any given arborvirus varied over the year and significantly correlated with rainfalls in the different areas (r = 0.61, p = 0.036). Finally, we found a significant correlation between the seroprevalence of antibodies against CHIKV and ONNV and the HIV-1 RNA plasma viral load. Thus, PLWHIV in Madagascar are highly exposed to various arboviruses. Further studies are needed to explain some of our findings. Full article

(This article belongs to the Special Issue Usutu Virus, West Nile Virus and Neglected Flaviviruses)

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22 pages, 1829 KiB

Open AccessSystematic Review

Inflammatory Response Associated with West Nile Neuroinvasive Disease: A Systematic Review

by Alessandro Pavesi, Giorgio Tiecco, Luca Rossi, Anita Sforza, Andrea Ciccarone, Federico Compostella, Sofia Lovatti, Lina Rachele Tomasoni, Francesco Castelli and Eugenia Quiros-Roldan

Viruses 2024, 16(3), 383; https://doi.org/10.3390/v16030383 - 29 Feb 2024

Cited by 1 | Viewed by 1895

Abstract

Background: West Nile virus (WNV) infection is a seasonal arbovirosis with the potential to cause severe neurological disease. Outcomes of the infection from WNV depend on viral factors (e.g., lineage) and host-intrinsic factors (e.g., age, sex, immunocompromising conditions). Immunity is essential to control the infection but may also prove detrimental to the host. Indeed, the persistence of high levels of pro-inflammatory cytokines and chemokines is associated with the development of blood–brain barrier (BBB) damage. Due to the importance of the inflammatory processes in the development of West Nile neuroinvasive disease (WNND), we reviewed the available literature on the subject. Methods: According to the 2020 updated PRISMA guidelines, all peer-reviewed articles regarding the inflammatory response associated with WNND were included. Results: One hundred and thirty-six articles were included in the data analysis and sorted into three groups (in vitro on-cell cultures, in vivo in animals, and in humans). The main cytokines found to be increased during WNND were IL-6 and TNF-α. We highlighted the generally small quantity and heterogeneity of information about the inflammatory patterns associated with WNND. Conclusions: Further studies are needed to understand the pathogenesis of WNND and to investigate the extent and the way the host inflammatory response either helps in controlling the infection or in worsening the outcomes. This might prove useful both for the development of target therapies and for the development of molecular markers allowing early identification of patients displaying an inflammatory response that puts them at a higher risk of developing neuroinvasive disease and who might thus benefit from early antiviral therapies. Full article

(This article belongs to the Special Issue Usutu Virus, West Nile Virus and Neglected Flaviviruses)

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9 pages, 758 KiB

Open AccessBrief Report

A Specific Pattern of Routine Cerebrospinal Fluid Parameters Might Help to Identify Cases of West Nile Virus Neuroinvasive Disease

by Johann Otto Pelz, Christoph Mühlberg, Isabel Friedrich, Lorenz Weidhase, Silke Zimmermann, Melanie Maier and Corinna Pietsch

Viruses 2024, 16(3), 341; https://doi.org/10.3390/v16030341 - 22 Feb 2024

Cited by 1 | Viewed by 1455

Abstract

Background: Viral meningitis/encephalitis (ME) is a rare but potentially harmful disease. The prompt identification of the respective virus is important to guide not only treatment but also potential public health countermeasures. However, in about 40% of cases, no virus is identified despite an extensive diagnostic workup. The aim of the present study was to analyze demographic, seasonal, and routine cerebrospinal fluid (CSF) parameters in cases of viral ME and assess their utility for the prediction of the causative virus. Methods: Demographic data, season, and routine CSF parameters (total leucocytes, CSF cell differentiation, age-adjusted CSF/serum albumin ratio, and total immunoglobulin ratios) were retrospectively assessed in cases of viral ME. Results: In total, 156 cases of acute viral ME (74 female, median age 40.0 years) were treated at a tertiary-care hospital in Germany. Specific viral infections were detected in 93 (59.6%) cases. Of these, 14 (9.0%) cases were caused by herpes simplex virus (HSV), 36 (23.1%) by varicella-zoster virus (VZV), 27 (17.3%) by enteroviruses, 9 (5.8%) by West Nile virus (WNV), and 7 (4.5%) by other specific viruses. Additionally, 64 (41.0%) cases of ME of unknown viral etiology were diagnosed. Cases of WNV ME were older, predominantly male, showed a severe disruption of the blood–CSF–barrier, a high proportion of neutrophils in CSF, and an intrathecal total immunoglobulin M synthesis in the first CSF sample. In a multinominal logistic regression analysis, the accuracy of these CSF parameters together with age and seasonality was best for the prediction of WNV (87.5%), followed by unknown viral etiology (66.7%), VZV (61.8%), and enteroviruses (51.9%). Conclusions: Cases with WNV ME showed a specific pattern of routine CSF parameters and demographic data that allowed for their identification with good accuracy. These findings might help to guide the diagnostic workup in cases with viral ME, in particular allowing the timely identification of cases with ME due to WNV. Full article

(This article belongs to the Special Issue Usutu Virus, West Nile Virus and Neglected Flaviviruses)

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