Sandfly fever Sicilian virus, Algeria.
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ABSTRACT:
SUBMITTER: Izri A
PROVIDER: S-EPMC2600228 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundMany studies have presented virus sequences which suggest the existence of a variety of putative new phleboviruses transmitted by sandflies in the Old World. However, in most of these studies, only partial sequences in the polymerase or the nucleoprotein genes were characterised. Therefore to further our understand of the presence and potential medical importance of sandfly-borne phleboviruses that circulate in southern Anatolia, we initiated field campaigns in 2012 and 2013 designed to identify, isolate and characterise phleboviruses in sandflies in this region.Methodology/principal findingsAn entomological investigation encompassing 8 villages in Adana, Mediterranean Turkey was performed in August and September 2012 and 2013. A total of 11,302 sandflies were collected and grouped into 797 pools which were tested for the presence of phleboviruses using specific primers for RT-PCR analysis and also cell culture methods for virus isolation. Seven pools were PCR positive, and viruses were isolated from three pools of sandflies, resulting in the identification of two new viruses that we named Zerdali virus and Toros virus. Phylogenetic analysis based on full-length genomic sequence showed that Zerdali virus was most closely related with Tehran virus (and belongs to the Sandfly fever Naples species), whereas Toros virus was closest to Corfou virus.Conclusions/significanceThe results indicate that a variety of phleboviruses are co-circulating in this region of southern Anatolia. Based on our studies, these new viruses clearly belong to genetic groups that include several human pathogens. However, whether or not Toros and Zerdali viruses can infect humans and cause diseases such as sandfly fever remains to be investigated.
| S-EPMC4805245 | biostudies-literature
Project description:Rift Valley fever virus (RVFV; genus Phlebovirus, family Bunyaviridae) is a mosquito-borne zoonotic pathogen which can cause hemorrhagic fever, neurological disorders or blindness in humans, and a high rate of abortion in ruminants. MP-12 strain, a live-attenuated candidate vaccine, is attenuated in the M- and L-segments, but the S-segment retains the virulent phenotype. MP-12 was manufactured as an Investigational New Drug vaccine by using MRC-5 cells and encodes a functional NSs gene, the major virulence factor of RVFV which 1) induces a shutoff of the host transcription, 2) inhibits interferon (IFN)-? promoter activation, and 3) promotes the degradation of dsRNA-dependent protein kinase (PKR). MP-12 lacks a marker for differentiation of infected from vaccinated animals (DIVA). Although MP-12 lacking NSs works for DIVA, it does not replicate efficiently in type-I IFN-competent MRC-5 cells, while the use of type-I IFN-incompetent cells may negatively affect its genetic stability. To generate modified MP-12 vaccine candidates encoding a DIVA marker, while still replicating efficiently in MRC-5 cells, we generated recombinant MP-12 encoding Punta Toro virus Adames strain NSs (rMP12-PTNSs) or Sandfly fever Sicilian virus NSs (rMP12-SFSNSs) in place of MP-12 NSs. We have demonstrated that those recombinant MP-12 viruses inhibit IFN-? mRNA synthesis, yet do not promote the degradation of PKR. The rMP12-PTNSs, but not rMP12-SFSNSs, replicated more efficiently than recombinant MP-12 lacking NSs in MRC-5 cells. Mice vaccinated with rMP12-PTNSs or rMP12-SFSNSs induced neutralizing antibodies at a level equivalent to those vaccinated with MP-12, and were efficiently protected from wild-type RVFV challenge. The rMP12-PTNSs and rMP12-SFSNSs did not induce antibodies cross-reactive to anti-RVFV NSs antibody and are therefore applicable to DIVA. Thus, rMP12-PTNSs is highly efficacious, replicates efficiently in MRC-5 cells, and encodes a DIVA marker, all of which are important for vaccine development for Rift Valley fever.
| S-EPMC3630143 | biostudies-other
Project description: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.
| S-EPMC7826795 | biostudies-literature
Project description:The sandfly-borne Toscana phlebovirus (TOSV), a close relative of the sandfly fever Sicilian phlebovirus (SFSV), is one of the most common causes of acute meningitis or meningoencephalitis in humans in the Mediterranean Basin. However, most of human phlebovirus infections in endemic areas either are asymptomatic or cause mild influenza-like illness. To date, a vertebrate reservoir for sandfly-borne phleboviruses has not been identified. Dogs are a prime target for blood-feeding phlebotomines and are the primary reservoir of human sandfly-borne Leishmania infantum. However, there are no definitive studies to assess whether dogs play a significant role as a reservoir host for human phlebovirus survival in the environment. Here, we have evaluated the susceptibility of domestic dogs to infection by TOSV and SFSV following the direct inoculation of the infectious virus. After experimental infection, the presence of viral RNA was investigated in plasma, urine, saliva, conjunctiva, faeces, semen, and bone marrow samples from 0 to 91 days postinoculation (dpi), as well as in plasma, saliva, and tears samples at 760 dpi. None of the challenged dogs developed clinical signs of infection with either TOSV or SFSV. SFSV RNA was never detected. TOSV RNA was not in any of the specimen types, except for plasma samples that showed low viral loads, although irregularly. None of the dogs developed detectable neutralizing antibodies after a single challenge dose of either TOSV or SFSV. However, a second challenge dose of virus given 56 days later elicited neutralizing antibodies, implying that the first inoculation of virus primed the animals for an anamnestic response following the second challenge. These results demonstrated that healthy domestic dogs are not highly susceptible to infection by TOSV or SFSV and do not develop significant viremia or excrete virus following infection. Consequently, dogs are unlikely natural reservoir hosts of infection and do not appear to play a significant role in phlebovirus transmission cycles.
| S-EPMC7232252 | biostudies-literature
Project description:BackgroundThe leishmaniases are a group of sandfly-transmitted diseases caused by species of the protozoan parasite, Leishmania. With an annual incidence of 1 million cases, 1 billion people living in Leishmania-endemic regions, and nearly 30,000 deaths each year, leishmaniasis is a major global public health concern. While phlebotomine sandflies are well-known as vectors of Leishmania, they are also the vectors of various phleboviruses, including Sandfly Fever Sicilian Virus (SFSV). Cutaneous leishmaniasis (CL), caused by Leishmania major (L. major), among other species, results in development of skin lesions on the infected host. Importantly, there exists much variation in the clinical manifestation between individuals. We propose that phleboviruses, vectored by and found in the same sandfly guts as Leishmania, may be a factor in determining CL severity. It was reported by our group that Leishmania exosomes are released into the gut of the sandfly vector and co-inoculated during blood meals, where they exacerbate CL skin lesions. We hypothesized that, when taking a blood meal, the sandfly vector infects the host with Leishmania parasites and exosomes as well as phleboviruses, and that this viral co-infection results in a modulation of leishmaniasis.Methodology/principal findingsIn vitro, we observed modulation by SFSV in MAP kinase signaling as well as in the IRF3 pathway that resulted in a pro-inflammatory phenotype. Additionally, we found that SFSV and L. major co-infection resulted in an exacerbation of leishmaniasis in vivo, and by using endosomal (Toll-like receptor) TLR3, and MAVS knock-out mice, deduced that SFSV's hyperinflammatory effect was TLR3- and MAVS-dependent. Critically, we observed that L. major and SFSV co-infected C57BL/6 mice demonstrated significantly higher parasite burden than mice solely infected with L. major. Furthermore, viral presence increased leukocyte influx in vivo. This influx was accompanied by elevated total extracellular vesicle numbers. Interestingly, L. major displayed higher infectiveness with coincident phleboviral infection compared to L. major infection alone.Conclusion/significanceOverall our work represents novel findings that contribute towards understanding the causal mechanisms governing cutaneous leishmaniasis pathology. Better comprehension of the potential role of viral co-infection could lead to treatment regimens with enhanced effectiveness.
| S-EPMC8341699 | biostudies-literature
Project description:In malaria-endemic regions, many medical facilities have limited capacity to diagnose non-malarial etiologies of acute febrile illness (AFI). As a result, the etiology of AFI is seldom determined, although AFI remains a major cause of morbidity in developing countries. An outbreak of AFI was reported in the Afar region of Ethiopia in August of 2011. Retrospectively, 12,816 suspected AFI cases were identified by review of medical records. Symptoms were mild and self-limiting within 3 days after the date of onset; no fatalities were identified. All initial test results of AFI patient specimens were negative for selected pathogens using standard microbiological and molecular techniques. High-throughput sequencing of nucleic acid extracts of serum specimens from 29 AFI cases identified 17 (59%) of 29 samples as positive for Sandfly Fever Sicilian Virus (SFSV). These results were further confirmed by specific reverse transcription polymerase chain reaction. This is the first study implicating SFSV as an etiological agent for AFI in Ethiopia.
| S-EPMC4257654 | biostudies-literature
Project description:Phleboviruses (order Bunyavirales, family Phenuiviridae) are globally emerging arboviruses with a wide spectrum of virulence. Sandfly fever Sicilian virus (SFSV) is one of the most ubiquitous members of the genus Phlebovirus and associated with a self-limited, incapacitating febrile disease in travellers and military troops. The phleboviral NSs protein is an established virulence factor, acting as antagonist of the antiviral interferon (IFN) system. Consistently, we previously reported that SFSV NSs targets the induction of IFN mRNA synthesis by specifically binding to the DNA-binding domain of the IFN transcription factor IRF3. Here, we further characterized the effect of SFSV and its NSs towards IFN induction, and evaluated its potential to affect the downstream IFN-stimulated signalling and the subsequent transactivation of antiviral interferon-stimulated genes (ISGs). We found that SFSV dampened, but did not entirely abolish type I and type III IFN induction. Furthermore, SFSV NSs did not affect IFN signalling, resulting in substantial ISG expression in infected cells. Hence, although SFSV targets IRF3 to reduce IFN induction, it is not capable of entirely disarming the IFN system in the presence of high basal IRF3 and/or IRF7 levels, and we speculate that this significantly contributes to its low level of virulence.
| S-EPMC8742993 | biostudies-literature
Project description:Sandfly fever Sicilian virus (SFSV) is one of the most widespread and frequently identified members of the genus Phlebovirus (order Bunyavirales, family Phenuiviridae) infecting humans. Being transmitted by Phlebotomus sandflies, SFSV causes a self-limiting, acute, often incapacitating febrile disease ("sandfly fever," "Pappataci fever," or "dog disease") that has been known since at least the beginning of the 20th century. We show that, similarly to other pathogenic phleboviruses, SFSV suppresses the induction of the antiviral type I interferon (IFN) system in an NSs-dependent manner. SFSV NSs interfered with the TBK1-interferon regulatory factor 3 (IRF3) branch of the RIG-I signaling pathway but not with NF-?B activation. Consistently, we identified IRF3 as a host interactor of SFSV NSs. In contrast to IRF3, neither the IFN master regulator IRF7 nor any of the related transcription factors IRF2, IRF5, and IRF9 were bound by SFSV NSs. In spite of this specificity for IRF3, NSs did not inhibit its phosphorylation, dimerization, or nuclear accumulation, and the interaction was independent of the IRF3 activation or multimerization state. In further studies, we identified the DNA-binding domain of IRF3 (amino acids 1 to 113) as sufficient for NSs binding and found that SFSV NSs prevented the association of activated IRF3 with the IFN-? promoter. Thus, unlike highly virulent phleboviruses, which either destroy antiviral host factors or sequester whole signaling chains into inactive aggregates, SFSV modulates type I IFN induction by directly masking the DNA-binding domain of IRF3.IMPORTANCE Phleboviruses are receiving increased attention due to the constant discovery of new species and the ongoing spread of long-known members of the genus. Outbreaks of sandfly fever were reported in the 19th century, during World War I, and during World War II. Currently, SFSV is recognized as one of the most widespread phleboviruses, exhibiting high seroprevalence rates in humans and domestic animals and causing a self-limiting but incapacitating disease predominantly in immunologically naive troops and travelers. We show how the nonstructural NSs protein of SFSV counteracts the upregulation of the antiviral interferon (IFN) system. SFSV NSs specifically inhibits promoter binding by IFN transcription factor 3 (IRF3), a molecular strategy which is unique among phleboviruses and, to our knowledge, among human pathogenic RNA viruses in general. This IRF3-specific and stoichiometric mechanism, greatly distinct from the ones exhibited by the highly virulent phleboviruses, correlates with the intermediate level of pathogenicity of SFSV.
| S-EPMC6232482 | biostudies-literature
Project description: Not available
| S-EPMC4734512 | biostudies-literature
Project description:Sandflies are widely distributed around the Mediterranean Basin. Therefore, human populations in this area are potentially exposed to sandfly-transmitted diseases, including those caused by phleboviruses. Whilst there are substantial data in countries located in the northern part of the Mediterranean basin, few data are available for North Africa. In this study, a total of 1489 sandflies were collected in 2008 in Tunisia from two sites, bioclimatically distinct, located 235 km apart, and identified morphologically. Sandfly species comprised Phlebotomus perniciosus (52.2%), Phlebotomus longicuspis (30.1%), Phlebotomus papatasi (12.0%), Phlebotomus perfiliewi (4.6%), Phlebotomus langeroni (0.4%) and Sergentomyia minuta (0.5%). PCR screening, using generic primers for the genus Phlebovirus, resulted in the detection of ten positive pools. Sequence analysis revealed that two pools contained viral RNA corresponding to a novel virus closely related to sandfly fever Naples virus. Virus isolation in Vero cells was achieved from one pool. Genetic and phylogenetic characterization based on sequences in the three genomic segments showed that it was a novel virus distinct from other recognized members of the species. This novel virus was provisionally named Punique virus. Viral sequences in the polymerase gene corresponding to another phlebovirus closely related to but distinct from sandfly fever Sicilian virus were obtained from the eight remaining positive pools.
| S-EPMC3496376 | biostudies-literature