Usutu Virus Infection

A special issue of Pathogens (ISSN 2076-0817). This special issue belongs to the section "Viral Pathogens".

Deadline for manuscript submissions: closed (31 October 2020) | Viewed by 13889

Special Issue Editors


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Virology Unit, Istituto Zooprofilattico Sperimentale dell'Abruzzo e del Molise “G. Caporale”, Teramo, Italy
Interests: diagnosis of viral infectious diseases via innovative molecular methods; coronaviruses; morbilliviruses; reverse genetics; swine influenza viruses; next generations sequencing; arbovirus; orbiviruses; West Nile virus; viral diagnostics; virus discovery; virus evolution; pathogenesis studies
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Guest Editor
Istituto Zooprofilattico Sperimentale dell’Abruzzo e del Molise G. Caporale, 64100 Teramo, Italy
Interests: arboviroses
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The Flavivirus genus, within the family Flaviviridae, includes over 50 arthropod-borne viruses, so called arboviruses. Yellow fever, after which the genus is named, was the first virus demonstrated to cause an arthropod-borne disease. Additional important human pathogens, including the four dengue viruses (DENV), Japanese encephalitis (JEV), West Nile (WNV), Zika (ZIKV), and tick-borne encephalitis viruses, belong to the genus.  Importantly, zoonotic flaviviruses constitutes one of the main challenges for human and animal health. DENV cause around 21.000 human deaths annually, and it is estimated that at least 120 countries have endemic Dengue viruses transmission; ZIKV was recently responsible in affected areas for microcephaly and other severe brain defects following infections of pregnant women. WNV has become more prominent as a zoonotic agent, particularly in Europe and North America, where infections in humans, horses and birds have been reported. Human infected with WNV may develop a mild flu-like illness consisting of symptoms such as malaise, eye pain, headache, myalgia, gastrointestinal discomfort, and rash. However, 1% of persons with clinical illness may develop neuroinvasive disease such as meningitis, encephalitis, and acute flaccid paralysis

USUV was discovered in 1959 from a mosquito of the Culex neavei species in South Africa and isolated by intracerebral inoculation of newborne mice. The natural life cycle of USUV is similar to WNV: it involves birds as reservoirs and ornithophilic mosquitoes as vectors like the common Culex pipiens. USUV was considered for decades as a flavivirus with low zoonotic potential. However, recent data from various European countries indicate that there also might be a much higher number of clinical neuro-invasive USUV infections in humans than assumed to date. As WNV, USUV circulates in multiple genetic lineages and according to recent surveillance studies, WNV and USUV are the most widespread mosquito-borne flaviviruses in Europe, with co-circulation in the same geographical areas.

Although over the last years some breakthroughs have been achieved, there are important gaps of knowledge regarding the pathogenesis and immunological mechanisms of USUV. In this perspective, knowledge regarding the interaction of pre-exisiting flavivirus immunity and USUV infection, or vice versa, is also lacking.   

In this issue, we would like to focus on all aspects of USUV that provide an update of our current knowledge of the disease and of the interaction of USUV with extant flaviviruses. Topics of interest include (but are not limited to) epidemiology, transmission pathways, vector competence, host–virus interactions, mechanisms of infection and viral spread, cell-virus interactions, disease dynamics, clinical aspects, pathology and standardization of pathological evaluation protocols, disease pathogenesis, factors responsible for virus virulence, virus persistence, immune responses correlated with protection and how these can be activated, and development and improvement of diagnostic techniques.

Dr. Alessio Lorusso
Dr. Giovanni Savini
Guest Editors

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Keywords

  • Usutu virus
  • USUV
  • flavivirus
  • epidemiology
  • pathogenesis
  • cell-virus interaction
  • pre-existing immunity
  • pathology
  • vectors
  • diagnosis
  • molecular epidemiology
  • clinical aspects
  • immune response
  • experimental models of infection

Published Papers (3 papers)

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Research

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14 pages, 1827 KiB  
Article
Akt Interacts with Usutu Virus Polymerase, and Its Activity Modulates Viral Replication
by Laura Albentosa-González, Rosario Sabariegos, Armando Arias, Pilar Clemente-Casares and Antonio Mas
Pathogens 2021, 10(2), 244; https://doi.org/10.3390/pathogens10020244 - 20 Feb 2021
Cited by 6 | Viewed by 2282
Abstract
Usutu virus (USUV) is a flavivirus that mainly infects wild birds through the bite of Culex mosquitoes. Recent outbreaks have been associated with an increased number of cases in humans. Despite being a growing source of public health concerns, there is yet insufficient [...] Read more.
Usutu virus (USUV) is a flavivirus that mainly infects wild birds through the bite of Culex mosquitoes. Recent outbreaks have been associated with an increased number of cases in humans. Despite being a growing source of public health concerns, there is yet insufficient data on the virus or host cell targets for infection control. In this work we have investigated whether the cellular kinase Akt and USUV polymerase NS5 interact and co-localize in a cell. To this aim, we performed co-immunoprecipitation (Co-IP) assays, followed by confocal microscopy analyses. We further tested whether NS5 is a phosphorylation substrate of Akt in vitro. Finally, to examine its role in viral replication, we chemically silenced Akt with three inhibitors (MK-2206, honokiol and ipatasertib). We found that both proteins are localized (confocal) and pulled down (Co-IP) together when expressed in different cell lines, supporting the fact that they are interacting partners. This possibility was further sustained by data showing that NS5 is phosphorylated by Akt. Treatment of USUV-infected cells with Akt-specific inhibitors led to decreases in virus titers (>10-fold). Our results suggest an important role for Akt in virus replication and stimulate further investigations to examine the PI3K/Akt/mTOR pathway as an antiviral target. Full article
(This article belongs to the Special Issue Usutu Virus Infection)
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15 pages, 282 KiB  
Article
Evidence of Exposure to USUV and WNV in Zoo Animals in France
by Orianne Constant, Karine Bollore, Marion Clé, Jonathan Barthelemy, Vincent Foulongne, Baptiste Chenet, David Gomis, Laurie Virolle, Serafin Gutierrez, Caroline Desmetz, Rayane Amaral Moares, Cécile Beck, Sylvie Lecollinet, Sara Salinas and Yannick Simonin
Pathogens 2020, 9(12), 1005; https://doi.org/10.3390/pathogens9121005 - 30 Nov 2020
Cited by 20 | Viewed by 3397
Abstract
West Nile virus (WNV) and Usutu virus (USUV) are zoonotic arboviruses. These flaviviruses are mainly maintained in the environment through an enzootic cycle involving mosquitoes and birds. Horses and humans are incidental, dead-end hosts, but can develop severe neurological disorders. Nevertheless, there is [...] Read more.
West Nile virus (WNV) and Usutu virus (USUV) are zoonotic arboviruses. These flaviviruses are mainly maintained in the environment through an enzootic cycle involving mosquitoes and birds. Horses and humans are incidental, dead-end hosts, but can develop severe neurological disorders. Nevertheless, there is little data regarding the involvement of other mammals in the epidemiology of these arboviruses. In this study, we performed a serosurvey to assess exposure to these viruses in captive birds and mammals in a zoo situated in the south of France, an area described for the circulation of these two viruses. A total of 411 samples comprising of 70 species were collected over 16 years from 2003 to 2019. The samples were first tested by a competitive enzyme-linked immunosorbent assay. The positive sera were then tested using virus-specific microneutralization tests against USUV and WNV. USUV seroprevalence in birds was 10 times higher than that of WNV (14.59% versus 1.46%, respectively). Among birds, greater rhea (Rhea Americana) and common peafowl (Pavo cristatus) exhibited the highest USUV seroprevalence. Infections occurred mainly between 2016–2018 corresponding to a period of high circulation of these viruses in Europe. In mammalian species, antibodies against WNV were detected in one dama gazelle (Nanger dama) whereas serological evidence of USUV infection was observed in several Canidae, especially in African wild dogs (Lycaon pictus). Our study helps to better understand the exposure of captive species to WNV and USUV and to identify potential host species to include in surveillance programs in zoos. Full article
(This article belongs to the Special Issue Usutu Virus Infection)

Review

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19 pages, 3375 KiB  
Review
Epidemiology of Usutu Virus: The European Scenario
by Tatjana Vilibic-Cavlek, Tamas Petrovic, Vladimir Savic, Ljubo Barbic, Irena Tabain, Vladimir Stevanovic, Ana Klobucar, Anna Mrzljak, Maja Ilic, Maja Bogdanic, Iva Benvin, Marija Santini, Krunoslav Capak, Federica Monaco, Eddy Listes and Giovanni Savini
Pathogens 2020, 9(9), 699; https://doi.org/10.3390/pathogens9090699 - 26 Aug 2020
Cited by 73 | Viewed by 7577
Abstract
Usutu virus (USUV) is an emerging arbovirus isolated in 1959 (Usutu River, Swaziland). Previously restricted to sub-Saharan Africa, the virus was introduced in Europe in 1996. While the USUV has received little attention in Africa, the virus emergence has prompted numerous studies with [...] Read more.
Usutu virus (USUV) is an emerging arbovirus isolated in 1959 (Usutu River, Swaziland). Previously restricted to sub-Saharan Africa, the virus was introduced in Europe in 1996. While the USUV has received little attention in Africa, the virus emergence has prompted numerous studies with robust epidemiological surveillance programs in Europe. The natural transmission cycle of USUV involves mosquitoes (vectors) and birds (amplifying hosts) with humans and other mammals considered incidental (“dead-end”) hosts. In Africa, the virus was isolated in mosquitoes, rodents and birds and serologically detected in horses and dogs. In Europe, USUV was detected in bats, whereas antibodies were found in different animal species (horses, dogs, squirrels, wild boar, deer and lizards). While bird mortalities were not reported in Africa, in Europe USUV was shown to be highly pathogenic for several bird species, especially blackbirds (Turdus merula) and great gray owls (Strix nebulosa). Furthermore, neurotropism of USUV for humans was reported for the first time in both immunocompromised and immunocompetent patients. Epizootics and genetic diversity of USUV in different bird species as well as detection of the virus in mosquitoes suggest repeated USUV introductions into Europe with endemization in some countries. The zoonotic potential of USUV has been reported in a growing number of human cases. Clinical cases of neuroinvasive disease and USUV fever, as well as seroconversion in blood donors were reported in Europe since 2009. While most USUV strains detected in humans, birds and mosquitoes belong to European USUV lineages, several reports indicate the presence of African lineages as well. Since spreading trends of USUV are likely to continue, continuous multidisciplinary interventions (“One Health” concept) should be conducted for monitoring and prevention of this emerging arboviral infection. Full article
(This article belongs to the Special Issue Usutu Virus Infection)
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