Sand Fly-Borne Phleboviruses, Volume II

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Insect Viruses".

Deadline for manuscript submissions: closed (30 November 2022) | Viewed by 13785

Special Issue Editors


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Istituto Zooprofilattico Sperimentale della Lombardia e dell’Emilia Romagna “Bruno Ubertini”, Brescia, Italy
Interests: mosquitoes; sand flies; arbovirus; flavivirus; Usutu virus; West Nile virus; phlebovirus; Toscana virus
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Guest Editor
College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, USA
Interests: ecology and epidemiology of rodent-borne viruses; arbovirus ecology and epidemiology; viral diagnosis; viral taxonomy; viral evolution; ecology of hantaviruses
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

New phleboviruses (genus Phlebovirus, family Phenuiviridae) are increasingly isolated, or simply detected, in sand flies in recent years. Despite the number of new isolated viruses, several features of this group remain enigmatic. Their cycle is often unresolved, some are described only in sand flies, and an association with one or more vertebrate hosts is not well defined, as are their persistence mechanisms in the environment.

Some of the sand fly-borne phleboviruses are pathogenic for humans, causing a self-limiting febrile illness or, occasionally, meningitis, but this is poorly characterized for most of them. The wide variation among different strains can be partially ascribed to their ability to reassort, which also is not yet well defined. A variety of different sand fly phleboviruses can circulate in the same place, providing the opportunity for genetic reassortment, a phenomenon that can have an important effect on the pathogenicity of these viruses.

This Special Issue aims to summarize recently available information about sand fly-borne phleboviruses, reporting newly discovered viruses or their detection in already reported geographic ranges, describing their ecology, mechanism of evolution and interaction with potential hosts, and, in particular, the characterization of their pathogenic potential for human and other vertebrates.  

Sub-topics of the Special Issue:

  1. Taxonomy of phleboviruses  
  2. Detection of phleboviruses in sand flies and vertebrates
  3. Sand fly-borne phlebovirus ecology  

Dr. Mattia Calzolari
Prof. Dr. Charles Calisher
Guest Editors

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Keywords

  • sand fly
  • phlebovirus
  • Toscana virus
  • sand fly fever Naples virus
  • sand fly fever Sicilian virus
  • Salehabad virus
  • genome segment reassortment
  • pathogenicity

Published Papers (9 papers)

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Research

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11 pages, 277 KiB  
Article
Comprehensive Cross-Sectional Evaluation of Human Sandfly-Borne Phlebovirus Exposure in an Endemic Region
by Ceylan Polat, Nazlı Ayhan, Mehmet Bakır Saygan, Sevilay Karahan, Remi Charrel and Koray Ergünay
Viruses 2023, 15(9), 1902; https://doi.org/10.3390/v15091902 - 09 Sep 2023
Viewed by 786
Abstract
Sandfly-borne phleboviruses are endemic in countries around the Mediterranean Basin and pose a significant health threat for populations, with symptoms spanning from febrile diseases to central nervous system involvement. We carried out a comprehensive cross-sectional screening via microneutralization (MN) assays for a quantitative [...] Read more.
Sandfly-borne phleboviruses are endemic in countries around the Mediterranean Basin and pose a significant health threat for populations, with symptoms spanning from febrile diseases to central nervous system involvement. We carried out a comprehensive cross-sectional screening via microneutralization (MN) assays for a quantitative assessment of neutralizing antibodies (NAs) to seven phleboviruses representing three distinct serocomplexes, using samples previously screened via immunofluorescence assays (IFAs) in Turkey, an endemic region with various phleboviruses in circulation. We detected NAs to three phleboviruses: Toscana virus (TOSV), sandfly fever Naples virus (SFNV), and sandfly fever Sicilian virus (SFSV), while assays utilizing Adana virus, Punique virus, Massilia virus, and Zerdali virus remained negative. The most frequently observed virus exposure was due to TOSV, with a total prevalence of 22.6%, followed by SFNV (15.3%) and SFSV (12.1%). For each virus, IFA reactivity was significantly associated with NA detection, and further correlated with NA titers. TOSV and SFSV seroreactivities were co-detected, suggesting exposure to multiple pathogenic viruses presumably due to shared sandfly vectors. In 9.6% of the samples, multiple virus exposure was documented. In conclusion, our findings demonstrate widespread exposure to distinct pathogenic phleboviruses, for which diagnostic testing and serological screening efforts should be directed. Full article
(This article belongs to the Special Issue Sand Fly-Borne Phleboviruses, Volume II)
16 pages, 1540 KiB  
Article
The Role of the Leishmania infantum Infected Dogs as a Potential Reservoir Host for Toscana Virus in a Zoonotic Visceral Leishmaniasis Focus of Northern Tunisia
by Khalil Dachraoui, Ifhem Chelbi, Imen Labidi, Raja Ben Osman, Aida Sayadi, Mourad Ben Said, Saifedine Cherni, Mohammed Abdo Saghir Abbas, Rémi Charrel and Elyes Zhioua
Viruses 2023, 15(4), 1012; https://doi.org/10.3390/v15041012 - 20 Apr 2023
Cited by 1 | Viewed by 1500
Abstract
The role of dogs as reservoir hosts for Toscana virus (TOSV) remains undetermined. This study investigated TOSV and Leishmania infantum infections in one healthy and three infected dogs with Leishmania (A, B, C) following natural exposition to sandfly bites in a focus of [...] Read more.
The role of dogs as reservoir hosts for Toscana virus (TOSV) remains undetermined. This study investigated TOSV and Leishmania infantum infections in one healthy and three infected dogs with Leishmania (A, B, C) following natural exposition to sandfly bites in a focus of zoonotic visceral leishmaniasis (ZVL) located in Northern Tunisia from June to October 2020. At the end of the exposition period, infected and healthy dogs were examined for TOSV and L. infantum infections by xenodiagnosis using a colony of Phlebotomus perniciosus. Pools of freshly engorged P. perniciosus at days 0 and those at days 7 post-feeding were screened for TOSV and L. infantum by nested PCR in the polymerase gene and kinetoplast minicircle DNA, respectively. In the exposure site, P. pernicious is the most abundant sandfly species. The infection rates of sandflies with TOSV and L. infantum were 0.10 and 0.05%, respectively. Leishmania infantum DNA and TOSV RNA were detected in P. perniciosus females fed on dog B and C, respectively. The isolation of TOSV in Vero cells was achieved from two pools containing P. perniciosus fed on dog C. No pathogens were detected in P. perniciosus females fed on dog A and on control dog. We report for the first time the reservoir competence of dog with ZVL in the transmission of TOSV to sandfly vectors in natural settings, in addition to its role as a main reservoir host of L. infantum. Full article
(This article belongs to the Special Issue Sand Fly-Borne Phleboviruses, Volume II)
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10 pages, 1277 KiB  
Communication
New Isolation of Ponticelli III Virus (Bunyavirales: Phenuiviridae) in Emilia-Romagna Region, Italy
by Mohamed Daoudi, Giuseppe Romeo, Katia Marzani, Angelica Petrella, Paolo Bonilauri, Davide Lelli, Ali Boumezzough, Samia Boussaa, Michele Dottori and Mattia Calzolari
Viruses 2023, 15(2), 422; https://doi.org/10.3390/v15020422 - 02 Feb 2023
Cited by 1 | Viewed by 1289
Abstract
The number of newly described sandfly-borne phleboviruses has been steadily growing in recent years. Some phleboviruses are human pathogens, but their health relevance is largely uncharacterized. We aimed to investigate the circulation of these viruses in the Emilia-Romagna region where several have already [...] Read more.
The number of newly described sandfly-borne phleboviruses has been steadily growing in recent years. Some phleboviruses are human pathogens, but their health relevance is largely uncharacterized. We aimed to investigate the circulation of these viruses in the Emilia-Romagna region where several have already been described. A total of 482 sandflies were collected in a site in Reggio Emilia in 2019 and 2020. Sandflies collected in 2020 were grouped in 21 pools with a maximum of 25 sandflies per pool, submitted to real time PCR, and isolated in Vero cell culture. Complete genome sequencing showed the isolation of a strain of a Ponticelli III virus. This virus, which belongs to the species Adana phlebovirus, differed in the M segment from the Ponticelli I and Ponticelli II viruses. Analysis performed on the genomic segments of the newly isolated virus compared with other phleboviruses highlighted a strong purifying selection in the L segments, and different substitution saturation, highest in the M segments. Future research should address the ecological processes driving the occurrence of these novel phleboviruses and their possible impact on public health. Full article
(This article belongs to the Special Issue Sand Fly-Borne Phleboviruses, Volume II)
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9 pages, 1229 KiB  
Article
Monitoring of Insecticide Resistance Mutations and Pathogen Circulation in Sand Flies from Emilia-Romagna, a Leishmaniasis Endemic Region of Northern Italy
by Sofia Balaska, Mattia Calzolari, Annalisa Grisendi, Mara Scremin, Michele Dottori, Konstantinos Mavridis, Romeo Bellini and John Vontas
Viruses 2023, 15(1), 148; https://doi.org/10.3390/v15010148 - 03 Jan 2023
Cited by 2 | Viewed by 1908
Abstract
The continuously expanding distribution of sand flies, proven vectors of Leishmania and of several phleboviruses, is a growing public health issue in Europe. Especially in Italy, visceral leishmaniasis (VL) is occurring with increasing incidence northward, in previously non-endemic provinces. Around the globe, disease [...] Read more.
The continuously expanding distribution of sand flies, proven vectors of Leishmania and of several phleboviruses, is a growing public health issue in Europe. Especially in Italy, visceral leishmaniasis (VL) is occurring with increasing incidence northward, in previously non-endemic provinces. Around the globe, disease elimination efforts largely focus on sand fly vector insecticidal control, often leading to the development of resistance. In Emilia-Romagna (ER), northern Italy, insecticides are heavily applied for agricultural and mosquito control, but not specifically against sand flies. Here, we investigated the sand fly species composition in certain environmental settings in ER provinces and monitored the presence of pyrethroid resistance mutations and pathogen circulation. Phlebotomus perfiliewi, a dominant vector of Leishmania infantum, was detected almost exclusively in the region. No mutations in the voltage-gated sodium channel gene, e.g., knock-down resistance mutations I1011M, L1014F/S, V1016G, or F1020S, were recorded. Pathogen monitoring revealed that almost 40% of the tested sand fly pools were positive for Leishmania, while the presence of Toscana and Fermo phleboviruses was also observed in much lower frequencies (≤3% positive pools). Regular epidemiological and entomological monitoring, alongside resistance surveillance, is highly recommended to ensure the sustainability and efficiency of vector control interventions. Full article
(This article belongs to the Special Issue Sand Fly-Borne Phleboviruses, Volume II)
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13 pages, 2539 KiB  
Article
Isolation and Identification of Sandfly-Borne Viruses from Sandflies Collected from June to August, 2019, in Yangquan County, China
by Qinyan Wang, Qikai Yin, Shihong Fu, Jingxia Cheng, Xiuyan Xu, Jing Wang, Bin Wu, Xiaodong Tian, Yan Li, Jing Lu, Ying He, Fan Li, Kai Nie, Songtao Xu, Xiaoqing Lu, Huanyu Wang, Bin Wang and Guodong Liang
Viruses 2022, 14(12), 2692; https://doi.org/10.3390/v14122692 - 30 Nov 2022
Cited by 3 | Viewed by 1039
Abstract
In Yangquan County, the sandfly-transmitted virus (Wuxiang virus) was first isolated from sandflies in 2018. However, relationships between the abundance and seasonal fluctuations of local sandflies and sandfly-transmitted viruses are unknown. Herein, we report that sandfly specimens were collected in three villages in [...] Read more.
In Yangquan County, the sandfly-transmitted virus (Wuxiang virus) was first isolated from sandflies in 2018. However, relationships between the abundance and seasonal fluctuations of local sandflies and sandfly-transmitted viruses are unknown. Herein, we report that sandfly specimens were collected in three villages in Yangquan County, from June to August, 2019. A total of 8363 sandflies were collected (June, 7927; July, 428; August, 8). Eighteen virus strains (June, 18; July, 0; August, 0) were isolated in pools of Phlebotomus chinensis. The genome sequence of the newly isolated virus strain was highly similar to that of the Wuxiang virus (WUXV), isolated from sandflies in Yangquan County in 2018. Our results suggested that the sandfly-transmitted viruses, and the local sandfly population, are stable in Yangquan County, and that June is the peak period for the virus carried by sandflies in this area. Full article
(This article belongs to the Special Issue Sand Fly-Borne Phleboviruses, Volume II)
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8 pages, 951 KiB  
Article
Sand Flies and Pathogens in the Lowlands of Emilia-Romagna (Northern Italy)
by Mattia Calzolari, Giuseppe Romeo, Martina Munari, Paolo Bonilauri, Roberta Taddei, Maria Sampieri, Simone Bariselli, Gianluca Rugna and Michele Dottori
Viruses 2022, 14(10), 2209; https://doi.org/10.3390/v14102209 - 07 Oct 2022
Cited by 4 | Viewed by 1652
Abstract
Cases of sand fly-borne diseases in the Emilia-Romagna region, such as meningitis caused by Toscana virus and human leishmaniasis, are reported annually through dedicated surveillance systems. Sand flies are abundant in the hilly part of the region, while the lowland is unsuitable habitat [...] Read more.
Cases of sand fly-borne diseases in the Emilia-Romagna region, such as meningitis caused by Toscana virus and human leishmaniasis, are reported annually through dedicated surveillance systems. Sand flies are abundant in the hilly part of the region, while the lowland is unsuitable habitat for sand flies, which are found in lower numbers in this environment with respect to the hilly areas. In this study, we retrieved sand flies collected during entomological surveillance of the West Nile virus (from 2018 to 2021) to assess their abundance and screen them for the presence of pathogens. Over the four-year period, we collected 3022 sand flies, more than half in 2021. The most abundant sand fly species was Phlebotomus (Ph.) perfiliewi, followed by Ph. perniciosus; while more rarely sampled species were Ph. papatasi, Ph. mascittii and Sergentomyia minuta. Sand flies were collected from the end of May to the end of September. The pattern of distribution of the species is characterized by an abundant number of Ph. perfiliewi in the eastern part of the region, which then falls to almost none in the western part of the region, while Ph. perniciosus seems more uniformly distributed throughout. We tested more than 1500 female sand flies in 54 pools to detect phleboviruses and Leishmania species using different PCR protocols. Toscana virus and Leishmania infantum, both human pathogens, were detected in 5 pools and 7 pools, respectively. We also detected Fermo virus, a phlebovirus uncharacterized in terms of relevance to public health, in 4 pools. We recorded different sand fly abundance in different seasons in Emilia-Romagna. During the season more favorable for sand flies, we also detected pathogens transmitted by these insects. This finding implies a health risk linked to sand fly-borne pathogens in the surveyed area in lowland, despite being considered a less suitable habitat for sand flies with respect to the hilly areas. Full article
(This article belongs to the Special Issue Sand Fly-Borne Phleboviruses, Volume II)
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13 pages, 2952 KiB  
Article
Endoplasmic Stress Affects the Coinfection of Leishmania Amazonensis and the Phlebovirus (Bunyaviridae) Icoaraci
by José V. dos Santos, Patricia F. Freixo, Áislan de C. Vivarini, Jorge M. Medina, Lucio A. Caldas, Marcia Attias, Karina L. Dias Teixeira, Teresa Cristina C. Silva and Ulisses G. Lopes
Viruses 2022, 14(9), 1948; https://doi.org/10.3390/v14091948 - 02 Sep 2022
Cited by 1 | Viewed by 1568
Abstract
Viral coinfections can modulate the severity of parasitic diseases, such as human cutaneous leishmaniasis. Leishmania parasites infect thousands of people worldwide and cause from single cutaneous self-healing lesions to massive mucosal destructive lesions. The transmission to vertebrates requires the bite of Phlebotomine sandflies, [...] Read more.
Viral coinfections can modulate the severity of parasitic diseases, such as human cutaneous leishmaniasis. Leishmania parasites infect thousands of people worldwide and cause from single cutaneous self-healing lesions to massive mucosal destructive lesions. The transmission to vertebrates requires the bite of Phlebotomine sandflies, which can also transmit Phlebovirus. We have demonstrated that Leishmania infection requires and triggers the Endoplasmic stress (ER stress) response in infected macrophages. In the present paper, we tested the hypothesis that ER stress is increased and required for the aggravation of Leishmania infection due to coinfection with Phlebovirus. We demonstrated that Phlebovirus Icoaraci induces the ER stress program in macrophages mediated by the branches IRE/XBP1 and PERK/ATF4. The coinfection with L. amazonensis potentiates and sustains the ER stress, and the inhibition of IRE1α or PERK results in poor viral replication and decreased parasite load in macrophages. Importantly, we observed an increase in viral replication during the coinfection with Leishmania. Our results demonstrated the role of ER stress branches IRE1/XBP1 and PERK/ATF4 in the synergic effect on the Leishmania increased load during Phlebovirus coinfection and suggests that Leishmania infection can also increase the replication of Phlebovirus in macrophages. Full article
(This article belongs to the Special Issue Sand Fly-Borne Phleboviruses, Volume II)
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Review

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17 pages, 1450 KiB  
Review
Sandfly-Borne Phleboviruses in Portugal: Four and Still Counting
by Fátima Amaro, Líbia Zé-Zé and Maria João Alves
Viruses 2022, 14(8), 1768; https://doi.org/10.3390/v14081768 - 13 Aug 2022
Cited by 1 | Viewed by 1986
Abstract
According to ICTV, there are currently 66 known phlebovirus species. More than 40 of these viruses were isolated or detected in phlebotomine sandflies and some of them are known pathogens. In Portugal, information about sandfly-borne phleboviruses is scarce and scattered sandfly-borne diseases are [...] Read more.
According to ICTV, there are currently 66 known phlebovirus species. More than 40 of these viruses were isolated or detected in phlebotomine sandflies and some of them are known pathogens. In Portugal, information about sandfly-borne phleboviruses is scarce and scattered sandfly-borne diseases are neglected and often not considered in differential diagnoses. The main objective of this work was to gather the existing information and to raise awareness about the circulating phleboviruses in this country. To date, Massilia and Alcube phleboviruses have been isolated from sandflies in southern Portugal. Human infections with Toscana and Sicilian phleboviruses have been reported, as well as seroprevalence in cats and dogs. More studies are needed in order to understand if the viruses isolated during the entomological surveys have an impact on human health and to fully understand the real importance of the already recognized pathogens in our country. Full article
(This article belongs to the Special Issue Sand Fly-Borne Phleboviruses, Volume II)
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Other

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3 pages, 176 KiB  
Commentary
Point Prevalence Studies Are Necessary as First Steps in Studying the Epidemiology of Viruses and Other Pathogens Transmitted by Arthropods
by Charles H. Calisher
Viruses 2022, 14(6), 1244; https://doi.org/10.3390/v14061244 - 08 Jun 2022
Viewed by 1183
Abstract
Studies of the epidemiology of arthropod-borne viruses are based on understanding whether a given virus is found in a particular location or locations, how prevalent the virus is in that area, which vertebrate hosts serve as reservoirs of the virus, the relationship between [...] Read more.
Studies of the epidemiology of arthropod-borne viruses are based on understanding whether a given virus is found in a particular location or locations, how prevalent the virus is in that area, which vertebrate hosts serve as reservoirs of the virus, the relationship between the size of the populations of these reservoirs and the prevalence of the virus and, of course, whether the virus causes human, livestock, or wildlife diseases, as well as other characteristics. However, seasonal conditions fluctuate, annual conditions fluctuate, human impacts alter the environment, and the habitat and ecosystems naturally change. Because these parameters provide a more encompassing view of the natural history of a virus, it is important to recognize that point prevalence studies comprise only a single view of the situation and that longitudinal studies are required to obtain a more complete and useful understanding of the natural history of the virus. This paper provides details as to whether and how to conduct such studies. Full article
(This article belongs to the Special Issue Sand Fly-Borne Phleboviruses, Volume II)
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