Sandfly-Borne Viruses of Demonstrated/Relevant Medical Importance

Sandflies show distribution in a vast geographical area from Europe to Asia, Africa, Australia, and Central and South America where they can transmit a large number of viruses. Between these viruses, the most important are grouped into the Phlebovirus genus (family Phenuiviridae). Among them, several sandfly-borne phleboviruses cause self-limiting febrile disease (sandfly fever) or central and peripheral nervous system infections. Data concerning the geographic distribution of these phleboviruses has drastically increased during the last decade in both the new and the old worlds. The current situation depicts a high viral diversity with taxonomic groups containing human pathogenic and non-pathogenic viruses. This merits to provide insight to address the question of medical and veterinary public health impact of all these viruses, which are poorly studied. To do so, integrated and translational approaches must use ecological, epidemiological, serological and direct clinical evidence. Beside, other viruses transmitted by sandflies and belonging to Rhabdoviridae and Reoviridae families can also be of veterinary and public health importance. The chapter aims to provide a comprehensive view of the sandfly-borne viral pathogens of the public health impact on humans and other vertebrates in the old and new worlds

Porfirazin esaslı süpramoleküler yapılar

Porphyrins, phthalocyanines, tetrabenzo porphyrins and porphyrazines which are tetrapyrrole derivatives. Because of both theoretical studies and applications in advanced materials science, tetrapyrrole derivatives receive extensive attention. Porphyrins are important not only from biological aspect but also for coordination chemistry as catalysis and material science. Phthalocyanines which are used in electro-photography, optic data collection, gas sensor, liquid crystal, laser technology and the photodynamic therapy of tumors as well as their classical fields as pigments and dyes, are completely synthetic materials. Porphyrazines that have functionalized groups at pheripheral positions have the potential to exhibit novel optical, magnetic and electronic properties. They also maintain some additional features superior to the values met in related materials. Additions of the transition metal ion in the inner core of a porphyrazine offer new ways to induce, modify and control molecular properties. The starting point for a novel porphyrazine structure with eight (1-naphthyl) groups bound to the periphery is 1,2-bi ( naphthyl )dinitrile which was obtained by oxidative coupling of 1-naphthylacetonitrile in the presence of I2. The solid product was obtained in a yield of 21%. It was a mixture of maleo-and fumaro-nitriles and the latter was present in higher ratio as expected from the presence of bulky naphthyl substituents. The mixture of maleo-and fumaro-nitrile reluctance to turn into porphyrazine under the usual conditions (i.e. Mg(OR)2 in refluxing propanol or butanol) points out the lower ratio of the maleonitrile component. This problem was solved by activation of the fumaronitrile derivative to the corresponding pyrroline derivative 3,4-(1-naphthyl)pyrroline-2,5-diimine which cyclizes quite easily to porphyrazine at reflux temperature of propanol or butanol. Conversion of 3,4-(1-naphthyl)pyrroline-2,5-diimine into porphyrazine was achieved by the template effect of magnesium butanolate. Cyclotetramerization gave green-colored octakis(1-naphthyl) porphyrazinato magnesium in yield (70%). It is soluble in chloroform, dichloromethane and acetone, but insoluble in apolar hydrocarbon solvents such as n-hexane. Intensive research interest on peripherally functionalized porphyra-zines during the last decade has shown that these tetrapyrrol derivatives should be considered in many respects as an alternative to phthalocyanines. The porphyrazine macrocycles afford a skilful platform to build up detailed molecular superstructures and this property coupled with a full and well-improved synthetic chemistry has surpassed to the synthesis of different catalytically essential metallo porphyrazines and original model compounds of various functions. In this study magnesium porphyrazinate substituted with eight (1-naphthyl) groups on the peripheral positions has been synthesized by cyclotetramerization of 3, 4-(1-naphthyl)pyrroline-2,5-diimine in the presence of magnesium butanolate. Its demetallation by treatment with trifluoroacetic acid result with a partially oxidized product, namely, octakis(1-naphthyl)-2-seco-porphyrazine-2,3-dione. Further reaction of this product with copper(II) acetate, zinc (II) acetate and cobalt (II) acetate led to the metallo derivatives, [octakis (1-naphthyl)-2-seco-2, 3-dioxoporphyrazinato]M (II) (M= Cu, Zn, Co). These new compounds have been characterized by elemental analysis, together with FT-IR, 1H NMR, UV-Vis and mass spectral data. Since naphthyl groups are comparable with dimethylamino groups as electron donors to 18-  electron system of the inner core , in the demetallation reaction, relatively strong acids (e.g. trifluoroacetic acid) inhibits the electron donating strength of the dimethylamino groups much more than naphthyls. Sterical tension due to the presence of eight bulky naphthalene units around the core might be another reason for the cleavage of one of pyrrol rings. These should be taken together with the oxidation resulting from singlet oxygen cycloaddition reactions as described in early works. The presence of an electron donating group on the periphery causes a bathochromic shift on Q bands. UV-Vis spectra of porphyrazines (1, 3-5 in CHCl3) prepared in the present work exhibited intense single Q band absorption of the   transitions around 632-644 nm and B bands in the UV region around 340-348 nm.For metal-free derivative (2), Q band is split into two peaks at 620 and 676 nm as a consequence of the lowering of the symmetry of porphyrazine core. In conclusion, new seco-porphyrazines with eight naphthyl groups have been described; Together with their high electron donating property, steric requirements of the eight bulky naphthyl substituents can be the reasons leading to oxidized seco-porphyrazines. Keywords: Seco-porphyrazine, porphyrazine, pyrroline, copper, zinc, cobalt. Porfirinler, ftalosiyaninler, tetrabenzo-porfirinler ve porfirazinler tetrapirol türevleridir. Bu yapılar, son yıllarda hem temel bilim hem de uygulamalı çalışmalar için üzerinde önemle durulan konulardan birini oluşturmaktadır. Porfirinler sadece biyoloji açısından önem taşımakla kalmayıp zengin koordinasyon kimyası, kataliz ve malzeme bilimindeki uygulamaları ile de ilgi çekmektedir. Ftalosiyaninler, tamamen sentetik ürünlerdir. Bunların boyar madde ve pigment olarak değerlendirilmesi yanında enerji dönüşümü, elektrofotografi, optik veri toplanması, gaz sensör, sıvı kristal, lazer teknolojisi için kızılötesi boyar madde ve tek boyutlu metaller gibi pek çok uygulaması bulunmaktadır. Fonksiyonel substitüent taşıyan porfirazinler üzerinde yoğun çalışmalar yapılmaktadır. Bu tetrapirol türevlerinin birçok açıdan fitalosiyaninlere alternatif olabileceği düşünülmektedir. Porfirazinlerin makrohalkaları oldukça işlevsel makro moleküllerin oluşturulmasını sağlar. Bu tür makrohalkalı bileşikler, biyolojik etkileri nedeniyle, oldukça önemli bileşiklerdir. Halka üyesi olarak azot, kükürt ve oksijen gibi atomları içeren heterohalkalı bileşikler hem endüstrinin çeşitli alanlarında hem de tıpta yaygın bir şekilde kullanılmaktadırlar. Bu çalışmada peripheral konumlarında sekiz adet naftil grubu bulunan magnezyum forfirazin 3,4-(1-naftil)pirolin-2,5-diimin’nin magnezyum butanolat mevcudiyetinde halkalaşması sonucu elde edilmiştir. Bu madde trifloroasetik asit ile işleme tabi tuturak metalsizleştirilmiştir. İşlem sonucunda kısmi oksitlenmiş bir bileşik olan oktakis(1-naftil)-2-seko-porfirazin-2,3-dion’un oluştuğu belirlenmiştir. Metalsiz seko-porfirazinin bakır(II) asetat, çinko(II) asetat ve kobalt(II) asetat ile reaksiyonundan metalli türevleri olan [oktakis(1-naftil)-2-seko-2,3-dioksopor-firazinat]M(II) bileşikleri elde edilmiştir (M=Cu, Zn, Co). Oluşturulan yeni bileşikler FT-IR, 1H NMR, UV-Vis ve kütle spektrumları alınarak elementel analizleri yapılarak karakterize edilmiştir. Anahtar Kelimeler: Seko-porfirazin, porfirazin, pirolin, bakır, çinko, kobalt

Human seroprevalence of Toscana virus and Sicilian phlebovirus in the southwest of Portugal

Funding Information: Fundação para a Ciência e a Tecnologia, I.P. (FCT) for funding through contract GHTM-UID/Multi/04413/2013 and Investigator Starting Grant IF/01302/2015. AP was supported by the Portuguese Ministry of Education and Science (via FCT) through a PhD grant (SFRH/BD/116516/2016). Publisher Copyright: © 2021, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.Toscana virus (TOSV) is emergent in the Mediterranean region and responsible for outbreaks of encephalitis or meningoencephalitis. Sicilian phlebovirus (SFSV) cause epidemics of febrile illness during the summer. The aim of this study was to evaluate the presence of antibodies against TOSV and SFSV in humans in the southwest of Portugal. Neutralizing antibodies to TOSV and SFSV were respectively detected in 5.3% and 4.3% out of 400 human sera tested highlighting the need to increase public health awareness regarding phleboviruses and to include them in the differential diagnosis in patients presenting with fever of short duration and neurological manifestations.publishersversionpublishe

Seroprevalence of toscana Virus and sandfly fever sicilian virus in European bat colonies measured using a neutralization test

Toscana phlebovirus (TOSV) and Sicilian phlebovirus (SFSV) are endemic in the Mediterranean area where they are transmitted to humans by infected sandflies. Vertebrates of several species have been postulated to act as reservoirs of these viruses, but convincing evidence is still awaited. Among them, bats have been suggested, however documented evidence is lacking. Here we tested a total of 329 bats belonging to eight species collected from twelve localities in southern Spain for the presence of neutralizing antibodies specific to TOSV and SFSV. Positive sera were detected in Schreiber's long-fingered bat (Miniopterus schreibersii), mouse-eared Myotis (Myotis myotis), European free-tailed bat (Tadarida teniotis), and common serotine (Eptesicus serotinus) with the latter showing the highest prevalence rates for SFSV (22.6%) and TOSV (10%). There was no difference between females and males. Results suggest that bats are not likely to play a major role in the natural cycle of these two sandfly-borne phleboviruses. However, large breeding colonies of bats can be used as sentinels for surveillance of the presence of such viruses in a given locality. In addition, capture-recapture studies should be initiated in order to understand better the dynamics of TOSV and SFSV in bat populations

Les Phlebovirus transmis par les phlébotomes dans les Balkans : isolement du virus, caractérisation, évolution et séroépidémiologie

Les phlébovirus présentent sont présents dans toutes les régions du globe. Certains phlébovirus transmis par phlébotomes provoquent une maladie fébrile et des infections du système nerveux central. Depuis, de plus en plus de données montrent que la péninsule des Balkans joue un rôle majeur dans l'émergence de maladies à transmission vectorielle. Au début de ce travail, on comptait un nombre très limité de phlébovirus identifiés et isolés dans cette région. Une étude intégrée et transdisciplinaire en vue d'un inventaire des virus circulant dans pays des Balkans. (i) Un total de 3,850 phlébotomes sont été recueillis dans sept pays des Balkans en 2014 et 2015. Ils ont été testés pour la présence d'ARN viral et inoculé sur des cellules VERO afin d'isoler le virus détecté; (ii) des études de séroprévalence utilisant des tests de neutralisation ont été effectuées sur des échantillons de bovins et de moutons pour évaluer à deux agents pathogènes humains : le virus Toscana (TOSV) et le virus Sandfly fever Sicilian virus (SFSV). Nos résultats se composent de (i) la découverte et le séquençage de 3 nouveaux phlébovirus appartenant à 2 espèces différentes, (ii) la première identification du genotype B de TOSV en Croatie, (iii) la preuve de la co-circulation de deux genotypes (B et C) de TOSV, (iv) des taux d'anticorps neutralisants qui sont beaucoup plus élevés chez les bovins et les moutons pour le SFSV que pour TOSV. En conclusion, les résultats obtenus au cours de ce travail démontrent qu’es les Balkans représentent une zone de très importante activité pour les phlebovirus et donc mérite une surveillance particulière à cause du risque d’émergence et de dissémination.Phleboviruses have a worldwide distribution. In the areas where sand flies are present, some of the sandfly-borne phleboviruses cause febrile illness and central nervous system infections. Sandfly fever was first reported in the Balkan Peninsula at the end of the 19th century. Since there is accumulating data showing that the Balkan peninsula plays a major role in the emergence of vector-borne diseases. At the outset of this work, a very limited number of phleboviruses had been identified and isolated in this region. To fill this gap, an integrated and transdisciplinary study was designed aiming at an inventory of viruses circulating in Balkans and associated seroprevalence studies using domestic animals: (i) a total of 3,850 sandflies were collected in seven Balkan countries (Albania, Bosnia-Herzegovina, Croatia, Kosovo, Montenegro, Republic of Macedonia and Serbia) in 2014 and 2015. They were tested for the presence of viral RNA and inoculated on VERO cell for virus isolation; (ii) seroprevalence studies using neutralisation tests were performed on cattle and sheep samples to assess the level of exposure to two human pathogens, Toscana virus (TOSV) and Sandfly fever Sicilian virus (SFSV). Our results consist of (i) the discovery and sequencing of 3 novel phleboviruses belonging to 2 different species, (ii) the identification for the first time of TOSV lineage B in Croatia, (iii) evidence of co-circulation of two lineages (Lineage B and C) of TOSV, (iv) rates of neutralising antibodies that are much higher in cattle and sheep for SFSV than for TOSV. Together the findings obtained during this work demonstrate that the Balkan area is a hot spot for phleboviruses

Emergent Sand Fly–Borne Phleboviruses in the Balkan Region

International audienceSand fly–borne phleboviruses are associated with febrile diseases and nervous system infections in the Mediterranean basin. Sandfly fever was first reported in the Balkan Peninsula at the end of the 19th century. Since then, accumulating data show that the Balkan Peninsula, as a transboundary region between Asia and Europe, plays a major role in the emergence of vectorborne diseases in Europe. To provide an inclusive approach, we collected published data on phleboviruses in the Balkan countries and used them to evaluate the impact of these pathogens from virologic, epidemiologic, and public health perspectives. Recent findings show a high diversity of phleboviruses belonging to 3 species or serocomplexes circulating heavily in the Balkans. Focusing on undisputable human pathogens, we found direct and indirect laboratory documentation for Toscana virus, Sandfly fever Sicilian virus, and Adria virus. These data demonstrate that the Balkans are a hotspot for phleboviruses transmitted by sand flies

Of phlebotomines (sandflies) and viruses: a comprehensive perspective on a complex situation

International audienceOld World sandfly-borne phleboviruses are classified into three serological complexes: Sandfly fever Sicilian, Sandfly fever Naples and Salehabad. Human pathogens (febrile illness ['sandfly fever'], neuroinvasive infections) belong to the two first complexes. The increasing number of newly discovered sandfly-borne phleboviruses raises concerns about their medical and veterinary importance. They occupy a wide geographic area from Mediterranean basin to North Africa and the Middle East to the central Asia. At least nine species of sandflies can transmit these viruses. Recent results suggest that sandfly vectors are not as specific for viruses as initially believed. Recent seroprevalence studies demonstrate that humans and domestic animals are heavily exposed. Specific molecular diagnostic methods must be developed and implemented in clinical microbiology laboratories

Chapter Sandfly-Borne Viruses of Demonstrated/Relevant Medical Importance

Sandflies show distribution in a vast geographical area from Europe to Asia, Africa, Australia, and Central and South America where they can transmit a large number of viruses. Between these viruses, the most important are grouped into the Phlebovirus genus (family Phenuiviridae). Among them, several sandfly-borne phleboviruses cause self-limiting febrile disease (sandfly fever) or central and peripheral nervous system infections. Data concerning the geographic distribution of these phleboviruses has drastically increased during the last decade in both the new and the old worlds. The current situation depicts a high viral diversity with taxonomic groups containing human pathogenic and non-pathogenic viruses. This merits to provide insight to address the question of medical and veterinary public health impact of all these viruses, which are poorly studied. To do so, integrated and translational approaches must use ecological, epidemiological, serological and direct clinical evidence. Beside, other viruses transmitted by sandflies and belonging to Rhabdoviridae and Reoviridae families can also be of veterinary and public health importance. The chapter aims to provide a comprehensive view of the sandfly-borne viral pathogens of the public health impact on humans and other vertebrates in the old and new worlds

An update on Toscana virus distribution, genetics, medical and diagnostic aspects

Background: Toscana virus is an arbovirus transmitted by sand flies within the Mediterranean area where it can cause febrile illness and neuroinvasive infections during the seasonal circulation period of the vector. Although it is an important cause of meningitis and encephalitis, it remains a neglected virus with limited published data, as demonstrated by <250 peer-reviewed articles since the 1970s. Objective: The last review article on Toscana virus was published in 2012. The aim was to compile peer-reviewed articles to provide an updated review highlighting recent findings to complement previous review articles. Sources: PubMed database was searched using the 'Toscana virus' keyword from 2010 to present. A total of 152 articles were retrieved and identified studies were assessed for novel information on virus genetics, and geographic and medical aspects compared with existing knowledge reported in previous review articles. Content: Studies addressing medical, veterinary and entomological aspects have provided evidence that Toscana virus is present in North Africa, in the Balkan Peninsula, and in most of the Mediterranean islands. Besides the two previously recognized genetic lineages, a novel evolutionary lineage has been identified in the Balkan Peninsula. Co-circulation of two genetic lineages has been demonstrated in France, in Turkey and in Croatia. In addition to meningitis and meningo-encephalitis, which have been reported for 40 years, various neuroinvasive forms have been recently reported such as Guillain-Barre syndrome, hydrocephalus, myositis, fasciitis, polymyeloradiculopathy, deafness and facial paralysis