-
Annals of the New York Academy of... Dec 2023Phleboviruses are zoonotic pathogens found in parts of Africa, Asia, Europe, and North America and cause disease symptoms ranging from self-limiting febrile illness to... (Review)
Review
Phleboviruses are zoonotic pathogens found in parts of Africa, Asia, Europe, and North America and cause disease symptoms ranging from self-limiting febrile illness to severe disease, including hemorrhagic diathesis, encephalitis, and ocular pathologies. There are currently no approved preventative vaccines against phlebovirus infection or antivirals for the treatment of the disease. Here, we discuss the roles of neutralizing antibodies in phlebovirus infection, the antigenic targets present on the mature polyproteins Gn and Gc, progress in vaccine development, and the prospects of identifying conserved neutralizing epitopes across multiple phleboviruses. Further research in this area will pave the way for the rational design of pan-phlebovirus vaccines that will protect against both known phleboviruses but also newly emerging phleboviruses that may have pandemic potential.
Topics: Humans; Phlebovirus; Immunity, Humoral; Asia; Vaccines; North America
PubMed: 37936483
DOI: 10.1111/nyas.15080 -
Enfermedades Infecciosas Y... 2021The genera Phlebovirus transmitted by Diptera belonging to the Psychodidae family are a cause of self-limited febrile syndrome in the Mediterranean basin in summer and... (Review)
Review
The genera Phlebovirus transmitted by Diptera belonging to the Psychodidae family are a cause of self-limited febrile syndrome in the Mediterranean basin in summer and autumn. Toscana virus can also cause meningitis and meningoencephalitis. In Spain, Toscana, Granada, Naples, Sicily, Arbia and Arrabida-like viruses have been detected. The almost widespread distribution of Phlebotomus genus vectors, and especially Phlebotomus perniciosus, in which several of these viruses have been detected, makes it very likely that there will be regular human infections in our country, with this risk considered moderate for Toscana virus and low for the other ones, in areas with the highest vector activity. Most of the infections would be undiagnosed, while only Toscana virus would have a greater impact due to the potential severity of the illness.
Topics: Animals; Humans; Insect Vectors; Phlebovirus; Psychodidae; Sandfly fever Naples virus; Spain
PubMed: 34353512
DOI: 10.1016/j.eimce.2021.05.001 -
Virologie (Montrouge, France) Jun 2019Phleboviruses constitute a large group of arthropod-borne viruses (arboviruses), mainly transmitted to their hosts by sandflies and ticks, occasionally by mosquitoes.... (Review)
Review
Phleboviruses constitute a large group of arthropod-borne viruses (arboviruses), mainly transmitted to their hosts by sandflies and ticks, occasionally by mosquitoes. These viruses have a worldwide distribution and many cause serious diseases - often fatal - in both domestic animals and humans. The global warming, the apparent wide distribution of arthropod reservoirs, and the increasing number of outbreaks show that phleboviruses must be taken seriously as emerging disease agents. This review proposes to focus on the early steps of phlebovirus infection, from virus binding to penetration into the cytosol. We address the most recent knowledge and advances in the entry of these viruses into vertebrate host cells, including virus receptors, cellular factors, endocytic pathways, and fusion.
Topics: Animals; Animals, Domestic; Arboviruses; Humans; Phlebovirus; Psychodidae; Ticks
PubMed: 31210134
DOI: 10.1684/vir.2019.0780 -
Advances in Experimental Medicine and... 2023Rift Valley fever virus (RVFV) is a member of the Phlebovirus genus, one of the 20 genera in the Phenuiviridae family. RVFV causes disease in animals and humans and is...
Rift Valley fever virus (RVFV) is a member of the Phlebovirus genus, one of the 20 genera in the Phenuiviridae family. RVFV causes disease in animals and humans and is transmitted by sandflies or ticks. However, research into RVFV is limited by the requirement for biosafety level 3 (BSL-3) containment. Pseudotyped virus overcomes this limitation as it can be handled in a BSL-2 environment. Pseudotyped RVFV possesses an identical envelope protein structure to that of the authentic virus, simulating the same process of receptor binding and membrane fusion to host cells. Pseudotyped phleboviruses are therefore useful tools to study the infection mechanism of these viruses and for the screening of inhibitory drugs and the development of therapeutic monoclonal antibodies.
Topics: Animals; Humans; Phlebovirus; Rift Valley Fever; Viral Pseudotyping; Rift Valley fever virus
PubMed: 36920701
DOI: 10.1007/978-981-99-0113-5_13 -
Viruses Jun 2021Severe fever with thrombocytopenia syndrome (SFTS) is an acute febrile illness characterized by fever, leukopenia, thrombocytopenia, and gastrointestinal symptoms such... (Review)
Review
Severe fever with thrombocytopenia syndrome (SFTS) is an acute febrile illness characterized by fever, leukopenia, thrombocytopenia, and gastrointestinal symptoms such as diarrhea, nausea, and vomiting resulting from infection with the SFTS virus (SFTSV). The SFTSV is transmitted to humans by tick bites, primarily from , , and . Human-to-human transmission has also been reported. Since the first report of an SFTS patient in China, the number of patients has also been increasing. The mortality rate of patients with SFTS remains high because the disease can quickly lead to death through multiple organ failure. In particular, an average fatality rate of approximately 20% has been reported for SFTS patients, and no treatment strategy has been established. Therefore, effective antiviral agents and vaccines are required. Here, we aim to review the epidemiology, clinical manifestations, laboratory diagnosis, and various specific treatments (i.e., antiviral agents, steroids, intravenous immunoglobulin, and plasma exchange) that have been tested to help to cope with the disease.
Topics: Animals; Antiviral Agents; Humans; Phlebovirus; Severe Fever with Thrombocytopenia Syndrome; Ticks
PubMed: 34201811
DOI: 10.3390/v13071213 -
Viruses Jul 2016Bunyaviruses are enveloped viruses with a tripartite RNA genome that can pose a serious threat to animal and human health. Members of the Phlebovirus genus of the family... (Review)
Review
Bunyaviruses are enveloped viruses with a tripartite RNA genome that can pose a serious threat to animal and human health. Members of the Phlebovirus genus of the family Bunyaviridae are transmitted by mosquitos and ticks to humans and include highly pathogenic agents like Rift Valley fever virus (RVFV) and severe fever with thrombocytopenia syndrome virus (SFTSV) as well as viruses that do not cause disease in humans, like Uukuniemi virus (UUKV). Phleboviruses and other bunyaviruses use their envelope proteins, Gn and Gc, for entry into target cells and for assembly of progeny particles in infected cells. Thus, binding of Gn and Gc to cell surface factors promotes viral attachment and uptake into cells and exposure to endosomal low pH induces Gc-driven fusion of the viral and the vesicle membranes. Moreover, Gn and Gc facilitate virion incorporation of the viral genome via their intracellular domains and Gn and Gc interactions allow the formation of a highly ordered glycoprotein lattice on the virion surface. Studies conducted in the last decade provided important insights into the configuration of phlebovirus Gn and Gc proteins in the viral membrane, the cellular factors used by phleboviruses for entry and the mechanisms employed by phlebovirus Gc proteins for membrane fusion. Here, we will review our knowledge on the glycoprotein biogenesis and the role of Gn and Gc proteins in the phlebovirus replication cycle.
Topics: Animals; Glycoproteins; Humans; Phlebovirus; Viral Envelope Proteins; Viral Proteins; Virus Assembly; Virus Internalization; Virus Release
PubMed: 27455305
DOI: 10.3390/v8070202 -
Viruses Nov 2023Rift Valley fever phlebovirus (RVFV) is a zoonotic pathogen that causes Rift Valley fever (RVF) in livestock and humans. Currently, there is no licensed human vaccine or...
Rift Valley fever phlebovirus (RVFV) is a zoonotic pathogen that causes Rift Valley fever (RVF) in livestock and humans. Currently, there is no licensed human vaccine or antiviral drug to control RVF. Although multiple species of animals and humans are vulnerable to RVFV infection, host factors affecting susceptibility are not well understood. To identify the host factors or genes essential for RVFV replication, we conducted CRISPR-Cas9 knockout screening in human A549 cells. We then validated the putative genes using siRNA-mediated knock-downs and CRISPR-Cas9-mediated knock-out studies. The role of a candidate gene in the virus replication cycle was assessed by measuring intracellular viral RNA accumulation, and the virus titers were analyzed using plaque assay or TCID assay. We identified approximately 900 genes with potential involvement in RVFV infection and replication. Further evaluation of the effect of six genes on viral replication using siRNA-mediated knock-downs revealed that silencing two genes ( and ) significantly impaired RVFV replication. For further analysis, we focused on the gene since the role of the gene in RVFV replication was previously described in detail. knockout A549 cell lines were generated and used to dissect the effect of on a bunyavirus, RVFV, and an orthobunyavirus, La Crosse encephalitis virus (LACV). We observed significant effects of knockout cells on both intracellular RVFV RNA levels and viral titers. At the intracellular RNA level, affected RVFV replication at a later phase of its replication cycle (24 h) when compared with the LACV replication, which was affected in an earlier replication phase (12 h). In summary, we identified as an essential host factor for the replication of two different viruses, RVFV and LACV, both of which belong to the order. Future studies will investigate the mechanistic role through which facilitates phlebovirus replication.
Topics: Animals; Humans; Rift Valley Fever; Rift Valley fever virus; Phlebovirus; Virus Replication; RNA, Small Interfering; Adaptor Proteins, Signal Transducing
PubMed: 38005928
DOI: 10.3390/v15112251 -
Veterinaria Italiana Jul 2023Phleboviruses are common human pathogens diffused on the Mediterranean area whose infection can cause the typical prodromal symptom of a mild three‑days fever. In...
Phleboviruses are common human pathogens diffused on the Mediterranean area whose infection can cause the typical prodromal symptom of a mild three‑days fever. In particular, Toscana Virus (TOSV) has a great concern since its capacity to provoke central nervous system disorders like meningoencephalitis. Furthermore, as the phlebotomine arthropod vectors represent the main carrier for pathogens of the genus Leishmania as well, the purpose of the study was to investigate the presence of TOSV in Lampedusa, Italy previously reported for leishmaniosis infection cases. The survey was carried out through an initial sampling phase of sand flies, by means of CDC light traps, and a second step of molecular analyses. The genomic S‑segment of TOSV was targeted. The positive samples were sequenced and compared with those available in GenBank™ using Basic Local Alignments Tool (BLAST) analyses. The study revealed for the first time the presence of TOSV in Lampedusa, Italy. The entomological studies directed on vectors are currently widely used in sand fly surveillance, and new data on TOSV are of public health concern.
Topics: Animals; Humans; Phlebovirus; Psychodidae; Phlebotomus; Italy; Meningoencephalitis
PubMed: 38376831
DOI: 10.12834/VetIt.2711.17825.2 -
Emerging Infectious Diseases Oct 2020We isolated 17 viral strains capable of causing cytopathic effects in mammalian cells and death in neonatal mice from sand flies in China. Phylogenetic analysis showed...
We isolated 17 viral strains capable of causing cytopathic effects in mammalian cells and death in neonatal mice from sand flies in China. Phylogenetic analysis showed that these strains belonged to the genus Phlebovirus. These findings highlight the need to control this potentially emerging virus to help safeguard public health.
Topics: Animals; China; Mice; Phlebovirus; Phylogeny; Psychodidae
PubMed: 32946723
DOI: 10.3201/eid2610.191374 -
Nature Microbiology Jan 2023Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease caused by a phlebovirus in the Bunyaviridae family. Infection can result in systemic...
Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease caused by a phlebovirus in the Bunyaviridae family. Infection can result in systemic inflammatory response syndrome with a high fatality rate, and there are currently no treatments or vaccines available. The microbiota has been implicated in host susceptibility to systemic viral infection and disease outcomes, but whether the gut microbiota is implicated in severe fever with thrombocytopenia syndrome virus (SFTSV) infection is unknown. Here, we analysed faecal and serum samples from patients with SFTS using 16S ribosomal RNA-sequencing and untargeted metabolomics, respectively. We found that the gut commensal Akkermansia muciniphila increased in relative abundance over the course of infection and was reduced in samples from deceased patients. Using germ-free or oral antibiotic-treated mice, we found that A. muciniphila produces the β-carboline alkaloid harmaline, which protects against SFTSV infection by suppressing NF-κB-mediated systemic inflammation. Harmaline indirectly modulated the virus-induced inflammatory response by specifically enhancing bile acid-CoA: amino acid N-acyltransferase expression in hepatic cells to increase conjugated primary bile acids, glycochenodeoxycholic acid and taurochenodeoxycholic acid. These bile acids induced transmembrane G-protein coupled receptor-5-dependent anti-inflammatory responses. These results indicate the probiotic potential of A. muciniphila in mitigating SFTSV infection.
Topics: Animals; Mice; Bunyaviridae Infections; Severe Fever with Thrombocytopenia Syndrome; Harmaline; Phlebovirus; Ticks
PubMed: 36604506
DOI: 10.1038/s41564-022-01279-6