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MSphere Sep 2020Sandfly-transmitted phleboviruses (family , order ) are associated with febrile illness and infections of the nervous system in humans. These viruses are almost...
Sandfly-transmitted phleboviruses (family , order ) are associated with febrile illness and infections of the nervous system in humans. These viruses are almost exclusively found in tropical areas of the New World and restricted to semiarid and temperate zones in the Old World. Here, we discovered seven strains of four previously unknown phleboviruses, named Bogoria virus (BOGV), Embossos virus (EMRV), Kiborgoch virus (KBGV), and Perkerra virus (PERV), as well as the recently discovered Ntepes virus, in sandflies collected in the Kenyan Rift Valley. The genomes have a tripartite organization with conserved termini typical of phleboviruses. LOBV, PERV, and EMBV showed low similarity to known phleboviruses, with less than 55% pairwise amino acid identities in the RNA-directed RNA polymerase (RdRp) proteins, and defined a highly diversified monophyletic clade in sister relationship to the sandfly fever Sicilian serocomplex. All three viruses failed to react with sandfly fever Sicilian virus antisera in recombinant immunofluorescence assays (rIFA), suggesting that the viruses belong to a yet-unknown serogroup. In contrast, KBGV was closely related to Toscana virus (84% identity of RdRp proteins) and shared a most recent common ancestor with the clade comprising sandfly fever Naples and Toscana viruses. KBGV reacted with sandfly fever Naples and Toscana virus antisera in rIFA. The genetic diversity of the detected viruses and their phylogenetic positions implies that the Old World sandfly-borne phleboviruses originated from sub-Saharan Africa. Importantly, our findings suggest that diseases associated with sandfly-borne phlebovirus infections may also affect the Kenyan population. Studies on the genetic diversity of arthropod-borne viruses circulating in rural regions can provide critical early indications on new emerging viruses essential for global epidemic preparedness. In this study, we describe the discovery of four phleboviruses in sandflies from the Kenyan Rift Valley. The novel viruses are related to the two medically important serocomplexes, sandfly fever Naples and sandfly fever Sicilian, that are associated with febrile illness and neuroinvasive infections and which were previously not known to occur in sub-Saharan Africa. Knowledge on the occurrence of sandfly-borne phleboviruses in Kenya and elsewhere in Africa can help to decipher their contributions in the etiologies of fevers of unknown origin in patients. Our findings on five genetically diverse phleboviruses detected in Kenya suggest that the common ancestor of Old World phleboviruses existed in sub-Saharan Africa, a hot spot for emerging arboviruses.
Topics: Animals; Evolution, Molecular; Genetic Variation; Humans; Kenya; Phlebotomus Fever; Phlebovirus; Phylogeny; Psychodidae; Sandfly fever Naples virus; Viral Proteins
PubMed: 32878929
DOI: 10.1128/mSphere.00598-20 -
Viruses Jul 2021The detection of phleboviruses (family: ) in human samples is challenged by the overall diversity and genetic complexity of clinically relevant strains, their...
The detection of phleboviruses (family: ) in human samples is challenged by the overall diversity and genetic complexity of clinically relevant strains, their predominantly nondescript clinical associations, and a related lack of awareness among some clinicians and laboratorians. Here, we seek to inform the detection of human phlebovirus infections by providing a brief introduction to clinically relevant phleboviruses, as well as key targets and approaches for their detection. Given the diversity of pathogens within the genus, this report focuses on diagnostic attributes that are generally shared among these agents and should be used as a complement to, rather than a replacement of, more detailed discussions on the detection of phleboviruses at the individual virus level.
Topics: Animals; Antibodies, Viral; Genetic Variation; Humans; Phlebotomus Fever; Phlebovirus; Phylogeny; Psychodidae; Viremia
PubMed: 34452365
DOI: 10.3390/v13081500 -
Parasites & Vectors Jul 2018High throughput sequencing (HTS) boosted the discovery of novel viruses and new variants of known viruses. Here we investigated the presence of viruses in 12 pools of...
BACKGROUND
High throughput sequencing (HTS) boosted the discovery of novel viruses and new variants of known viruses. Here we investigated the presence of viruses in 12 pools of sand flies captured in three climatic periods in RAPELD grids at Rio Claro, Chapada dos Guimarães and at Pirizal, North Pantanal, Mato Grosso State, Midwestern Brazil by HTS, viral isolation of a putative Phlebovirus positive pool in Vero cells, RT-PCR and transmission electron microscopy (TEM).
RESULTS
One pool containing three Lutzomyia (Lutzomyia) longipalpis sand flies captured in the transitional climatic period in North Pantanal showed a tripartite genomic sequence of a putative novel Phlebovirus belonging to the phlebotomus fever serogroup. Phylogenetic analysis revealed this virus is closely related and share a common ancestor with phleboviruses included in the same clade: Chagres, Urucuri and Uriurana virus. RNA-dependent RNA polymerase (RdRP) presented 60%, 59% and 58% of amino-acid (aa) similarity with these phleboviruses, respectively. Similarity of Nucleoprotein and NSs protein codified by ambissense strategy of segment S was of 49% and 37%, respectively, with the proteins of the closest phlebovirus, Uriurana virus. Glycoproteins (G1, G2) and NSm protein presented 49% and 48% aa similarity with Chagres and Uriurana virus, respectively. Uriurana virus was isolated from sand flies in Brazilian Amazon and Urucuri from rodents in Utinga forest, Pará State. Chagres virus is an arbovirus responsible for outbreaks of febrile illness in Panama. This phlebovirus was isolated in Vero cells, confirmed by TEM and RT-PCR for the L segment of the virus, and named Viola phlebovirus.
CONCLUSIONS
HTS, viral isolation, RT-PCR and TEM showed the presence of one virus in sand flies from North Pantanal with identity to a putative novel Phlebovirus from phlebotomus fever serogroup, named Viola phlebovirus.
Topics: Animals; Brazil; Chlorocebus aethiops; Phlebovirus; Phylogeny; Psychodidae; Vero Cells
PubMed: 29996902
DOI: 10.1186/s13071-018-2985-3 -
BioMed Research International 2022Phleboviruses transmitted by sandflies are among emerging public health threats. A novel named Ntepes virus (NTPV) was recently described and found to infect humans...
Phleboviruses transmitted by sandflies are among emerging public health threats. A novel named Ntepes virus (NTPV) was recently described and found to infect humans from a wide geographic area in Kenya. However, the entomologic risk factors of this virus such as the potential vectors and the transmission cycles remain poorly defined. This study assessed the ability of the colonized sandfly to transmit NTPV and determined the bloodmeal host sources of field-collected sandflies from the area where NTPV was found in Baringo County, Kenya. Five-day old laboratory-reared were orally challenged with an infectious dose of NTPV (≈10 pfu/ml) and incubated for up to 15 days postinfection. Individual sandflies were dissected into abdomens, legs, and salivary glands and screened for the virus infection by cell culture. Of the 205 virus-exposed sandflies, 19.5% developed non-disseminated infections in the midgut, with no evidence of virus dissemination or transmission in legs and salivary glands, respectively. The midgut infection rates decreased with increasing extrinsic incubation period (Spearman's correlation, = -0.71). Blood-fed specimens analyzed by polymerase chain reaction (PCR) and sequencing of a region of the mitochondrial 12S rRNA, revealed almost exclusive feeding on humans (98%) represented by the sandflies , , and One specimen of had fed on cattle (2%). These findings suggest is an incompetent laboratory vector of NTPV. The high human-feeding rate by diverse sandfly species increases the likelihood of human exposure to pathogens associated with these sandflies. Assessment of the susceptibility of species to NTPV is recommended given their high human-feeding tendency.
Topics: Humans; Cattle; Animals; Phlebotomus; Psychodidae; Phlebovirus; Kenya; Habits
PubMed: 36312854
DOI: 10.1155/2022/4231978 -
Clinical Infectious Diseases : An... Sep 2014Heartland virus (HRTV) is a tick-borne phlebovirus recently described in Missouri that is associated with fever, leukopenia, and thrombocytopenia. The virus has also...
BACKGROUND
Heartland virus (HRTV) is a tick-borne phlebovirus recently described in Missouri that is associated with fever, leukopenia, and thrombocytopenia. The virus has also been detected in Ambylomma americanum ticks.
METHODS
Here we report the first fatal case of HRTV disease in an 80-year-old Tennessee resident. He was hospitalized with fever, confusion, leukopenia, and thrombocytopenia and developed multiorgan failure and hemorrhage. A tick-borne illness was suspected and testing for ehrlichiosis was negative. He died on hospital day 15, and autopsy specimens were tested for various pathogens as part of an unexplained death evaluation.
RESULTS
HRTV antigens were detected in postmortem spleen and lymph nodes by immunohistochemistry, and HRTV was detected in premortem blood by reverse transcription polymerase chain reaction and by isolation in cell culture.
CONCLUSIONS
This case demonstrates that HRTV infection can cause severe disease and death and expands the geographic range of HRTV within the United States.
Topics: Aged, 80 and over; Fatal Outcome; Humans; Male; Phlebotomus Fever; Phlebovirus; Pulmonary Disease, Chronic Obstructive; Risk Factors; Serotyping; Tennessee
PubMed: 24917656
DOI: 10.1093/cid/ciu434 -
Journal of Medical Virology Aug 2021Severe fever with thrombocytopenia syndrome (SFTS) is recognized as an emerging infectious disease. This study aimed to investigate the pathogenic mechanism of SFTS. A...
Severe fever with thrombocytopenia syndrome (SFTS) is recognized as an emerging infectious disease. This study aimed to investigate the pathogenic mechanism of SFTS. A total of 100 subjects were randomly included in the study. Cytokine levels were detected by enzyme-linked immunosorbent assay and the viral load was detected by micro drop digital PCR. The results showed that levels of interleukin-6 (IL-6), IL-8, IL-10, IFN-inducible protein-10 (IP-10), monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1α (MIP-1α), transforming growth factor-β1 (TGF-β1), and regulated upon activation normal T cell expressed and secreted factor (RANTES) differed significantly among the SFTS patient group, healthy people group, and asymptomatic infection group (p < .05). Compared to the healthy people group, the patient group had increased cytokine levels (IL-6, IL-10, IP-10, MCP-1, and IFN-γ) but reduced levels of IL-8, TGF-β1, and RANTES (p < .0167). IL-6, IL-8, IL-10, IP-10, MCP-1, MIP-1α, TGF-β1, and the RANTES levels had different trends after the onset of the disease. IL-6, IL-10, IP-10, and MCP-1 levels in severe patients were higher than those in mild patients (p < .05). There was a positive correlation between viral load and IL-6 and IP-10 but a negative correlation between viral load and RANTES. SFTSV could cause a cytokine change: the cytokine levels of patients had different degrees of fluctuation after the onset of the disease. The levels of IL-6 and IL-8 in the asymptomatic infection group were found between the SFTS patients group and the healthy people group. The levels of IL-6, IL-10, IP-10, and MCP-1 in the serum could reflect the severity of the disease, and the levels of IL-6, IP-10, and RANTES were correlated with the viral load.
Topics: Aged; Cytokines; Enzyme-Linked Immunosorbent Assay; Female; Humans; Male; Middle Aged; Phlebovirus; Severe Fever with Thrombocytopenia Syndrome; Severity of Illness Index; Viral Load
PubMed: 33590892
DOI: 10.1002/jmv.26877 -
Viruses Aug 2022In the last decade, several phleboviruses transmitted by sand flies were detected in the Mediterranean countries, with the health impact of some of them being unknown....
In the last decade, several phleboviruses transmitted by sand flies were detected in the Mediterranean countries, with the health impact of some of them being unknown. From September to October 2020, a total of 3351 sand flies were captured in Kherrata (Bejaia, northern Algeria) and identified by sex, grouped in 62 pools, which were tested for the presence of phlebovirus RNA using endpoint RT-PCR. Two pools (male and female, respectively) were positive. The genome sequencing and phylogenetic analysis showed that the two phleboviruses detected were closely related to the Punique virus (PUNV) isolated in Tunisia and detected in Algeria. Both PUNV strains were isolated on VERO cells from positive pools. Morphological identification of 300 sand flies randomly selected, showed a clear dominance of (98.67%). The dominance of this species in the study area was confirmed by PCR targeting the mitochondrial DNA. Our result represents the first isolation of PUNV and the second report in Algeria from two distinct regions which confirm its large circulation in the country and more broadly in North Africa. Further studies are needed to measure the impact on public health through seroprevalence studies in humans as well as animals and to investigate its potential involvement in neurological viral diseases.
Topics: Algeria; Animals; Chlorocebus aethiops; Female; Male; Phlebovirus; Phylogeny; Psychodidae; Seroepidemiologic Studies; Tunisia; Vero Cells
PubMed: 36016418
DOI: 10.3390/v14081796 -
Journal of Korean Medical Science Jun 2013
Topics: Animals; Humans; Insect Bites and Stings; Phlebotomus Fever; Phlebovirus; Ticks
PubMed: 23772137
DOI: 10.3346/jkms.2013.28.6.795 -
The Journal of Biological Chemistry Jun 2019Heartland virus (HRTV) is a pathogenic phlebovirus recently identified in the United States and related to severe fever with thrombocytopenia syndrome virus (SFTSV)...
Heartland virus (HRTV) is a pathogenic phlebovirus recently identified in the United States and related to severe fever with thrombocytopenia syndrome virus (SFTSV) emerging in Asia. We previously reported that SFTSV disrupts host antiviral responses directed by interferons (IFNs) and their downstream regulators, signal transducer and activator of transcription (STAT) proteins. However, whether HRTV infection antagonizes the IFN-STAT signaling axis remains unclear. Here, we show that, similar to SFTSV, HRTV also inhibits IFN-α- and IFN-λ-mediated antiviral responses. As expected, the nonstructural protein (NSs) of HRTV (HNSs) robustly antagonized both type I and III IFN signaling. Protein interaction analyses revealed that a common component downstream of type I and III IFN signaling, STAT2, is the target of HNSs. Of note, the DNA-binding and linker domains of STAT2 were required for an efficient HNSs-STAT2 interaction. Unlike the NSs of SFTSV (SNSs), which blocks both STAT2 and STAT1 nuclear accumulation, HNSs specifically blocked IFN-triggered nuclear translocation only of STAT2. However, upon HRTV infection, IFN-induced nuclear translocation of both STAT2 and STAT1 was suppressed, suggesting that STAT1 is an additional HRTV target for IFN antagonism. Consistently, despite HNSs inhibiting phosphorylation only of STAT2 and not STAT1, HRTV infection diminished both STAT2 and STAT1 phosphorylation. These results suggest that HRTV antagonizes IFN antiviral signaling by dampening both STAT2 and STAT1 activities. We propose that HNSs-specific targeting of STAT2 likely plays an important role but is not all of the "tactics" of HRTV in its immune evasion.
Topics: Antiviral Agents; Bunyaviridae Infections; Cell Nucleus; Host-Pathogen Interactions; Humans; Immune Evasion; Interferon Type I; Interferons; Phlebovirus; Phosphorylation; Protein Transport; STAT1 Transcription Factor; STAT2 Transcription Factor; Signal Transduction; Interferon Lambda
PubMed: 31040183
DOI: 10.1074/jbc.RA118.006563 -
Emerging Infectious Diseases Dec 2022Severe fever with thrombocytopenia syndrome virus (SFTSV) is a tickborne bandavirus mainly transmitted by Haemaphysalis longicornis ticks in East Asia, mostly in rural...
Severe fever with thrombocytopenia syndrome virus (SFTSV) is a tickborne bandavirus mainly transmitted by Haemaphysalis longicornis ticks in East Asia, mostly in rural areas. As of April 2022, the amplifying host involved in the natural transmission of SFTSV remained unidentified. Our epidemiologic field survey conducted in endemic areas in China showed that hedgehogs were widely distributed, had heavy tick infestations, and had high SFTSV seroprevalence and RNA prevalence. After experimental infection of Erinaceus amurensis and Atelerix albiventris hedgehogs with SFTSV, we detected robust but transitory viremias that lasted for 9-11 days. We completed the SFTSV transmission cycle between hedgehogs and nymph and adult H. longicornis ticks under laboratory conditions with 100% efficiency. Furthermore, naive H. longicornis ticks could be infected by SFTSV-positive ticks co-feeding on naive hedgehogs; we confirmed transstadial transmission of SFTSV. Our study suggests that the hedgehogs are a notable wildlife amplifying host of SFTSV in China.
Topics: Animals; Severe Fever with Thrombocytopenia Syndrome; Hedgehogs; Seroepidemiologic Studies; Phylogeny; Phlebovirus; Ticks; China
PubMed: 36417938
DOI: 10.3201/eid2812.220668