Search

ABSTRACT Sandfly-transmitted phleboviruses (family Phenuiviridae, order Bunyavirales) 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. IMPORTANCE 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.

Sand 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.

Two captive cheetahs from a zoo in Japan died of a severe fever with thrombocytopenia syndrome–like illness. Severe fever with thrombocytopenia syndrome virus, an endemic tickborne phlebovirus, was detected systemically with secretion of infectious viruses into the saliva. These cases highlight the risk for exposure of captive animals to endemic arthropodborne pathogens.

Heartland virus is a suspected tickborne pathogen in the United States. We describe a case of hemophagocytic lymphohistiocytosis, then death, in an immunosuppressed elderly man in Missouri, USA, who was infected with Heartland virus.

Abstract Background Different phleboviruses are important pathogens for humans; most of these viruses are transmitted by sand flies. An increasing number of new phleboviruses have been reported over the past decade, especially in Mediterranean countries, mainly via their detection in sand flies. Results At least five different phleboviruses co-circulated in sand flies that were collected in three sites in Emilia-Romagna (Italy) in the summer of 2013. The well-known Toscana virus (TOSV) was isolated; three new, closely related phleboviruses differing in their M segments and tentatively named Ponticelli I, Ponticelli II and Ponticelli III virus, respectively, were isolated; a fifth putative phlebovirus, related to the sand fly fever Naples phlebovirus species, was also detected. The co-circulation, in a restricted area, of three viruses characterized by different M segments, likely resulted from reassortment events. According to the phylogenetic analysis of complete genome sequences, the TOSV belongs to clade A, together with other Italian isolates, while the Ponticelli viruses fall within the Salehabad phlebovirus species. Conclusions Results highlight an unexpected diversity of phleboviruses that co-circulate in the same area, suggesting that interactions likely occur amongst them, that can present challenges for their correct identification. The co-circulation of different phleboviruses appears to be common, and the bionomics of sand fly populations seem to play a relevant role. Such a complex situation emphasizes the need for detailed investigations of the biology of these viruses to better characterize their pathogenic potential for mammals, including humans.

Toscana virus (TOSV) is a prominent arthropod‐borne viral agent of human central nervous system infections occurring in the Mediterranean region. The main transmission route to susceptible individuals involves sandflies as vectors. Despite several reports revealing widespread TOSV activity in Turkey, vectors remained unidentified. A sandfly field survey was carried out in five provinces in Central, Southeast and Mediterranean Anatolia in 2017 to identify TOSV and related sandfly‐borne phleboviruses and Leishmania parasites, with evidence for circulation in the region. A total of 7136 sandfly specimens, collected via standard methods, were evaluated in 163 pools. TOSV was detected in 11 pools (6.7%), comprising Phlebotomus major sensu lato, Sergentomyia dentata and Phlebotomus papatasi species. TOSV partial L and S segment sequences were characterized, that phylogenetically clustered with local and global genotype A strains. An amino acid substitution outside the conserved motifs of the viral polymerase, also present in previous TOSV sequences in endemic regions, was observed. Leishmania tropica was detected in a single pool of Ph. sergentii (0.6%). This is the first report of TOSV in sandflies from Turkey, and this study further provides evidence for additional sandfly species with the potential to transmit TOSV. [ABSTRACT FROM AUTHOR]

Severe fever with thrombocytopenia syndrome (SFTS) is associated with a high mortality caused by rapidly progressive multiple organ failure. SFTS virus induces immunosuppression, mediated by interleukin-10 production, reduction of CD3+ and CD4+ T cells, and cytokine storms, and this may lead to various complications in critical SFTS patients. Recently, there have been reports of cases of invasive pulmonary Aspergillosis (IPA) in patients with SFTS in the absence of predisposing factors of IPA. However, there is no known relationship between SFTS and mycosis. Here, we report a SFTS patient with a low CD4+ T-cell count and a high viral load, who developed possible IPA in the absence of common risk factors for mycosis. This case adds to the evidence that IPA may occur as a complication of SFTS. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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–Barré syndrome, hydrocephalus, myositis, fasciitis, polymyeloradiculopathy, deafness and facial paralysis. Because it is endemic in countries bordering the Mediterranean, physicians should include Toscana virus in the differential diagnosis of patients presenting with febrile illness and/or neurological manifestations. [ABSTRACT FROM AUTHOR]

In 2018, Heartland disease virus infected 2 persons in Illinois, USA. In 2019, ticks were collected at potential tick bite exposure locations and tested for Heartland and Bourbon viruses. A Heartland virus-positive pool of adult male Amblyomma americanum ticks was found at 2 locations, 439 km apart, suggesting widespread distribution in Illinois. [ABSTRACT FROM AUTHOR]

Background: Tick-borne phenuivirus (TBPVs) comprise human and animal viruses that can cause a variety of clinical syndromes ranging from self-limiting febrile illness to fatal haemorrhagic fevers. Objective: Detect Phlebovirus (Family Phenuiviridae) in ticks collected from domestic animals in Córdoba, Colombia. Methods: We collected 2365 ticks from domestic animals in three municipalities of the Department of Cordoba, Colombia in 2016. Ticks were identified and pooled by species for RNA extraction. A nested real-time PCR with specific primers for Phlebovirus and a specific probe for Heartland virus (HRTV) formerly a Phlebovirus, now a Banyangvirus were performed. Also, a conventional nested PCR, with the same specific primers was used to detect other Phleboviruses, with positive reactions indicated by an amplified cDNA fragment of approximately 244 bp determined by gel electrophoresis. These bands were gel-purified and sequenced by the Sanger method. Results: Using real-time RT-PCR, no positive results for HRTV were found. However, using conventional nested PCR 2.2% (5/229 pools) yielded a product of 244 bp. One positive sample was detected in a pool of Dermacentor nitens ticks collected from a horse, and the four remaining positive pools were from Rhipicephalus microplus collected from cattle. The five positive nucleotide sequences had identities of 93 to 96% compared to a section of the L-segment of Lihan Tick virus, a Phlebovirus originally detected in R. microplus ticks in China. The strongest identity (96–99%) was with Lihan Tick virus detected in R. microplus ticks from Brazil. Conclusions: This is the first report of viral detection in ticks in Colombia. We detected a Colombian strain of Lihan Tick virus. We recommend expanding the sampling area and carrying out more eco-epidemiological studies related to epidemiological surveillance of viruses on ticks in Colombia. [ABSTRACT FROM AUTHOR]

Background Heartland virus (HRTV) was first described as a human pathogen in 2012. From 2013 to 2017, the Centers for Disease Control and Prevention (CDC) implemented a national protocol to evaluate patients for HRTV disease, better define its geographic distribution, epidemiology, and clinical characteristics, and develop diagnostic assays for this novel virus. Methods Individuals aged ≥12 years whose clinicians contacted state health departments or the CDC about testing for HRTV infections were screened for recent onset of fever with leukopenia and thrombocytopenia. A questionnaire was administered to collect data on demographics, risk factors, and signs and symptoms; blood samples were tested for the presence of HRTV RNA and neutralizing antibodies. Results Of 85 individuals enrolled and tested, 16 (19%) had evidence of acute HRTV infection, 1 (1%) had past infection, and 68 (80%) had no infection. Patients with acute HRTV disease were residents of 7 states, 12 (75%) were male, and the median age (range) was 71 (43–80) years. Illness onset occurred from April to September. The majority reported fatigue, anorexia, nausea, headache, confusion, arthralgia, or myalgia. Fourteen (88%) cases were hospitalized; 2 (13%) died. Fourteen (88%) participants reported finding a tick on themselves in the 2 weeks before illness onset. HRTV-infected individuals were significantly older (P < .001) and more likely to report an attached tick (P = .03) than uninfected individuals. Conclusions Health care providers should consider HRTV disease testing in patients with an acute febrile illness with either leukopenia or thrombocytopenia not explained by another condition or who were suspected to have a tickborne disease but did not improve following appropriate treatment. [ABSTRACT FROM AUTHOR]

Background: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease. SFTS is caused by the SFTS virus, a novel phlebovirus, and is spread by ticks. Methods: A 50-year-old man was admitted to our hospital with the chief complaint of fever and was diagnosed with confirmed SFTS. An epidemiological investigation was conducted, and immunofluorescent antibody assays (IFAs) were performed to determine the role of the patient's three dogs in the transmission. PCR assays were performed using ticks that were collected with the dragging and flagging method from the patient's dogs and home. Results: PCR results were positive, and IFA confirmed an increased antibody titer. Although the reverse transcription PCR results of the three dogs were negative for SFTS virus, one dog had an elevated SFTS IFA immunoglobulin G (IgG) titer of 1:1,024. Moreover, a number of ticks were observed in the area surrounding the dog cages. Based on the findings of the patient interview, the patient was likely to have acquired SFTS by blood splash because he removed or burst ticks from the dogs with his bare hands. Although no tick bites were reported, tick transmission could not be ruled out. Studies have shown that only one in three individuals with a diagnosis of SFTS recalls a tick bite; thus, a definite exclusion of tick transmission in this case was not possible. Conclusions: The epidemiological findings of our case suggest a possible relationship between tick infestation in domestic dogs and SFTS virus transmission to humans. However, there is no direct evidence supporting this viral transmission route. Future studies are needed to further investigate a potential route of SFTS transmission by exposure to engorged tick blood or pet dogs. [ABSTRACT FROM AUTHOR]

Sloths are genetically and physiologically divergent mammals. Phleboviruses are major arthropod‐borne viruses (arboviruses) causing disease in humans and other animals globally. Sloths host arboviruses, but virus detections are scarce. A phlebovirus termed Anhanga virus (ANHV) was isolated from a Brazilian Linnaeus's two‐toed sloth (Choloepus didactylus) in 1962. Here, we investigated the presence of phleboviruses in sera sampled in 2014 from 74 Hoffmann's two‐toed (Choloepus hoffmanni, n = 65) and three‐toed (Bradypus variegatus, n = 9) sloths in Costa Rica by broadly reactive RT‐PCR. A clinically healthy adult Hoffmann's two‐toed sloth was infected with a phlebovirus. Viral load in this animal was high at 8.5 × 107 RNA copies/ml. The full coding sequence of the virus was determined by deep sequencing. Phylogenetic analyses and sequence distance comparisons revealed that the new sloth virus, likely representing a new phlebovirus species, provisionally named Penshurt virus (PEHV), was most closely related to ANHV, with amino acid identities of 93.1%, 84.6%, 94.7% and 89.0% in the translated L, M, N and NSs genes, respectively. Significantly more non‐synonymous mutations relative to ANHV occurred in the M gene encoding the viral glycoproteins and in the NSs gene encoding a putative interferon antagonist compared to L and N genes. This was compatible with viral adaptation to different sloth species and with micro‐evolutionary processes associated with immune evasion during the genealogy of sloth‐associated phleboviruses. However, gene‐wide mean dN/dS ratios were low at 0.02–0.15 and no sites showed significant evidence for positive selection, pointing to comparable selection pressures within sloth‐associated viruses and genetically related phleboviruses infecting hosts other than sloths. The detection of a new phlebovirus closely‐related to ANHV, in sloths from Costa Rica fifty years after and more than 3,000 km away from the isolation of ANHV confirmed the host associations of ANHV‐related phleboviruses with the two extant species of two‐toed sloths. [ABSTRACT FROM AUTHOR]

Severe fever with thrombocytopenia syndrome (SFTS) is associated with a high mortality caused by rapidly progressive multiple organ failure. SFTS virus induces immunosuppression, mediated by interleukin-10 production, reduction of CD3+ and CD4+ T cells, and cytokine storms, and this may lead to various complications in critical SFTS patients. Recently, there have been reports of cases of invasive pulmonary Aspergillosis (IPA) in patients with SFTS in the absence of predisposing factors of IPA. However, there is no known relationship between SFTS and mycosis. Here, we report a SFTS patient with a low CD4+ T-cell count and a high viral load, who developed possible IPA in the absence of common risk factors for mycosis. This case adds to the evidence that IPA may occur as a complication of SFTS. [ABSTRACT FROM AUTHOR]

A significant increase in the number of viruses causing unexpected illnesses and epidemics among humans, wildlife and livestock has been observed in recent years. These new or re-emerging viruses have often caught the scientific community off-guard, without sufficient knowledge to combat them, as shown by the current coronavirus pandemic. The bunyaviruses, together with the flaviviruses and filoviruses, are the major etiological agents of viral hemorrhagic fever, and several of them have been listed as priority pathogens by the World Health Organization for which insufficient countermeasures exist. Based on new techniques allowing rapid analysis of the repertoire of protective antibodies induced during infection, combined with atomic-level structural information on viral surface proteins, structural vaccinology is now instrumental in the combat against newly emerging threats, as it allows rapid rational design of novel vaccine antigens. Here, we discuss the contribution of structural vaccinology and the current challenges that remain in the search for an efficient vaccine against some of the deadliest bunyaviruses.

Phleboviruses are arboviruses transmitted by sand flies, mosquitoes and ticks. Some sand fly-borne phleboviruses cause illnesses in humans, such as the summer fevers caused by the Sicilian and Naples viruses or meningitis caused by the Toscana virus. Indeed, traces of several phleboviral infections have been serologically detected in domestic animals, but their potential pathogenic role in vertebrates other than humans is still unclear, as is the role of vertebrates as potential reservoirs of these viruses. In this study, we report the results of a serological survey performed on domestic animals sampled in Northern Italy, against four phleboviruses isolated from sand flies in the same area. The sera of 23 dogs, 165 sheep and 23 goats were tested with a virus neutralization assay for Toscana virus, Fermo virus, Ponticelli I virus and Ponticelli III virus. Neutralizing antibodies against one or more phleboviruses were detected in four out of 23 dogs, 31 out of 165 sheep and 12 out of 23 goats. This study shows preliminary evidence for the distribution pattern of phleboviral infections in different animal species, highlighting the potential infection of the Toscana virus in dogs and the Fermo virus in goats.

Sand flies transmit Leishmania infantum, which is responsible for causing leishmaniasis, as well as many phleboviruses, including the human pathogenic Toscana virus. We screened sand flies collected from a single site between 2017 and 2020 for the presence of both phleboviruses and Leishmania. The sand flies were sampled with attractive carbon dioxide traps and CDC light traps between May and October. We collected more than 50,000 sand flies; 2826 were identified at the species level as Phlebotomus perfiliewi (98%) or Phlebotomus perniciosus (2%). A total of 16,789 sand flies were tested in 355 pools, and phleboviruses were found in 61 pools (6 Toscana virus positive pools, 2 Corfou virus positive pools, 42 Fermo virus positive pools, and 7 Ponticelli virus positive pools, and 4 unidentified phlebovirus positive pools). Leishmania was found in 75 pools and both microorganisms were detected in 16 pools. We isolated nine phleboviruses from another 2960 sand flies (five Ponticelli viruses and for Fermo viruses), not tested for Leishmania; the complete genome of a Fermo virus isolate was sequenced. The simultaneous detection in space and time of the Fermo virus and L. infantum is evidence that supports the co-circulation of both microorganisms in the same location and partial overlap of their cycles. A detailed characterization of the epidemiology of these microorganisms will support measures to limit their transmission.

Phleboviruses (genus Phlebovirus, family Phenuiviridae) are emerging pathogens of humans and animals. Sand-fly-transmitted phleboviruses are found in Europe, Africa, the Middle East, and the Americas, and are responsible for febrile illness and nervous system infections in humans. Rio Grande virus (RGV) is the only reported phlebovirus in the United States. Isolated in Texas from southern plains woodrats, RGV is not known to be pathogenic to humans or domestic animals, but serologic evidence suggests that sheep (Ovis aries) and horses (Equus caballus) in this region have been infected. Rift Valley fever virus (RVFV), a phlebovirus of Africa, is an important pathogen of wild and domestic ruminants, and can also infect humans with the potential to cause severe disease. The introduction of RVFV into North America could greatly impact U.S. livestock and human health, and the development of vaccines and countermeasures is a focus of both the CDC and USDA. We investigated the potential for serologic reagents used in RVFV diagnostic assays to also detect cells infected with RGV. Western blots and immunocytochemistry assays were used to compare the antibody detection of RGV, RVFV, and two other New World phlebovirus, Punta Toro virus (South and Central America) and Anhanga virus (Brazil). Antigenic cross-reactions were found using published RVFV diagnostic reagents. These findings will help to inform test interpretation to avoid false positive RVFV diagnoses that could lead to public health concerns and economically costly agriculture regulatory responses, including quarantine and trade restrictions.

Abstract Background Recently, Balkan virus (BALKV, family Phenuiviridae, genus Phlebovirus) was discovered in sand flies collected in Albania and genetically characterised as a member of the Sandfly fever Naples species complex. To gain knowledge concerning the geographical area where exposure to BALKV exists, entomological surveys were conducted in 2014 and 2015, in Croatia, Bosnia and Herzegovina (BH), Kosovo, Republic of Macedonia and Serbia. Results A total of 2830 sand flies were trapped during 2014 and 2015 campaigns, and organised as 263 pools. BALKV RNA was detected in four pools from Croatia and in one pool from BH. Phylogenetic relationships were examined using sequences in the S and L RNA segments. Study of the diversity between BALKV sequences from Albania, Croatia and BH showed that Albanian sequences were the most divergent (9–11% [NP]) from the others and that Croatian and BH sequences were grouped (0.9–5.4% [NP]; 0.7–5% [L]). The sand fly infection rate of BALKV was 0.26% in BH and 0.27% in Croatia. Identification of the species content of pools using cox1 and cytb partial regions showed that the five BALKV positive pools contained Phlebotomus neglectus DNA; in four pools, P neglectus was the unique species, whereas P. tobbi DNA was also detected in one pool. Conclusions We report here (i) the first direct evidence that the Balkan virus initially described in coastal Albania has a much wider dissemination area than originally believed, (ii) two real-time RT-PCR assays that may be useful for further screening of patients presenting with fever of unknown origin that may be caused by Balkan virus infection, (iii) entomological results suggesting that Balkan virus is likely transmitted by Phlebotomus neglectus, and possibly other sand fly species of the subgenus Larroussius. So far, BALKV has been detected only in sand flies. Whether BALKV can cause disease in humans is unknown and remains to be investigated.

Abstract Background Ticks are involved with the transmission of several viruses with significant health impact. As incidences of tick-borne viral infections are rising, several novel and divergent tick- associated viruses have recently been documented to exist and circulate worldwide. This study was performed as a cross-sectional screening for all major tick-borne viruses in several regions in Turkey. Next generation sequencing (NGS) was employed for virus genome characterization. Ticks were collected at 43 locations in 14 provinces across the Aegean, Thrace, Mediterranean, Black Sea, central, southern and eastern regions of Anatolia during 2014–2016. Following morphological identification, ticks were pooled and analysed via generic nucleic acid amplification of the viruses belonging to the genera Flavivirus, Nairovirus and Phlebovirus of the families Flaviviridae and Bunyaviridae, followed by sequencing and NGS in selected specimens. Results A total of 814 specimens, comprising 13 tick species, were collected and evaluated in 187 pools. Nairovirus and phlebovirus assays were positive in 6 (3.2%) and 48 (25.6%) pools. All nairovirus sequences were closely-related to the Crimean-Congo hemorrhagic fever virus (CCHFV) strain AP92 and formed a phylogenetically distinct cluster among related strains. Major portions of the CCHFV genomic segments were obtained via NGS. Phlebovirus sequencing revealed several tick-associated virus clades, including previously-characterized Antigone, Lesvos, KarMa and Bole tick viruses, as well as a novel clade. A wider host range for tick-associated virus strains has been observed. NGS provided near-complete sequences of the L genomic segments of Antigone and KarMa clades, as well as Antigone partial S segment. Co- infections of CCHFV and KarMa or novel phlebovirus clades were detected in 2.1% of the specimens. Conclusions Widespread circulation of various tick-associated phlebovirus clades were documented for the first time in Anatolia. Genomes of CCHFV AP92 strains were identified in previously unexplored locations. NGS provided the most detailed genomic characterization of the Antigone and KarMa viruses to date. The epidemiological and health-related consequences must be elucidated.

Toscana and sandfly fever Sicilian viruses (TOSV and SFSV, respectively), both transmitted by sand flies, are prominent human pathogens in the Old World. Of 1,086 serum samples collected from cattle and sheep during 2013 in various regions of Kosovo (Balkan Peninsula), 4.7% and 53.4% had neutralizing antibodies against TOSV and SFSV, respectively.

Severe fever with thrombocytopenia syndrome (SFTS), a tick-borne zoonotic disease, is caused by infection with SFTS virus (SFTSV). A previous study reported that human-to-human direct transmission of SFTSV can occur. However, potential animal-to-animal transmission of SFTSV without ticks has not been fully clarified. Thus, the objective of this study was to investigate potential mice-to-mice transmission of SFTSV by co-housing three groups of mice [i.e., wild-type mice (WT), mice injected with an anti-type I interferon-α receptor-blocking antibody (IFNAR Ab), and mice with knockout of type I interferon-α receptor (IFNAR KO)] as spreaders or recipients with different immune competence. As a result, co-housed IFNAR Ab and IFNAR KO mice showed body weight loss with SFTS viral antigens detected in their sera, extracorporeal secretions, and various organs. Based on histopathology, white pulp atrophy in the spleen was observed in all co-housed mice except WT mice. These results obviously show that IFNAR Ab and IFNAR KO mice, as spreaders, exhibited higher transmissibility to co-housed mice than WT mice. Moreover, IFNAR KO mice, as recipients, were more susceptible to SFTSV infection than WT mice. These findings suggest that type I interferon signaling is a pivotal factor in mice intraspecies transmissibility of SFTSV in the absence of vectors such as ticks.

We herein report a case of severe fever with thrombocytopenia syndrome (SFTS) with Pasteurella multilocida bacteremia in a 65-year-old man with alcoholic cirrhosis who was admitted to our hospital with anorexia and severe fatigue. Laboratory tests revealed pancytopenia and liver and kidney dysfunction. After admission, he developed impaired consciousness, mucosal hemorrhaging, and septic shock. SFTS virus was detected on polymerase chain reaction testing of blood and throat swabs, and Pasteurella multocida was detected on blood culture. Despite being treated with invasive mechanical ventilation, vasopressors, and antibiotics, the patient's condition progressively deteriorated, and he died four days after admission.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne hemorrhagic fever disease with high fatality rate of 10%-20%. Vaccines or specific therapeutic measures remain lacking. Human interferon inducible transmembrane protein 3 (hIFITM3) is a broad-spectrum antiviral factor targeting viral entry. However, the antiviral activity of hIFITM3 against SFTS virus (SFTSV) and the functional mechanism of IFITM3 remains unclear. Here we demonstrate that endogenous IFITM3 provides protection against SFTSV infection and participates in the anti-SFTSV effect of type Ⅰ and Ⅲ interferons (IFNs). IFITM3 overexpression exhibits anti-SFTSV function by blocking Gn/Gc-mediated viral entry and fusion. Further studies showed that IFITM3 binds SFTSV Gc directly and its intramembrane domain (IMD) is responsible for this interaction and restriction of SFTSV entry. Mutation of two neighboring cysteines on IMD weakens IFITM3-Gc interaction and attenuates the antiviral activity of IFITM3, suggesting that IFITM3-Gc interaction may partly mediate the inhibition of SFTSV entry. Overall, our data demonstrate for the first time that hIFITM3 plays a critical role in the IFNs-mediated anti-SFTSV response, and uncover a novel mechanism of IFITM3 restriction of SFTSV infection, highlighting the potential of clinical intervention on SFTS disease., (© 2024 Wiley Periodicals LLC.)

Objective: This study aimed to investigate the clinical characteristics of severe fever with thrombocytopenia syndrome complicated by viral myocarditis (SFTS-VM) and analyze relevant influencing factors., Methods: Retrospective analysis was conducted on clinical data from 79 SFTS-VM patients, categorized into common (SFTS-CVM, n = 40) and severe groups (SFTS-SVM, n = 39). Clinical manifestations, laboratory results, cardiac ultrasonography, and electrocardiogram features were analyzed. Univariate and multivariate analyses identified significant indicators, which were further assessed using ROC curves to predict SFTS-SVM., Results: SFTS-SVM group exhibited higher rates of hypotension, shock, abdominal pain, cough with sputum, and consciousness disorders compared to SFTS-CVM group. Laboratory findings showed elevated platelet count, ALT, AST, amylase, lipase, LDH, D-dimer, procalcitonin, TNI, and NT-proBNP in SFTS-SVM. Abnormal electrocardiograms, especially atrial fibrillation, were more prevalent in SFTS-SVM (P < 0.05). Multivariate analysis identified elevated LDH upon admission (OR = 1.004, 95% CI: 1-1.008, P = 0.050), elevated NT-proBNP (OR = 1.005, 95% CI: 1.001-1.008, P = 0.007), and consciousness disorders (OR = 112.852, 95% CI: 3.676 ~ 3464.292, P = 0.007) as independent risk factors for SFTS-SVM. LDH and NT-proBNP had AUCs of 0.728 and 0.744, respectively, in predicting SFTS-SVM. Critical values of LDH (> 978.5U/L) and NT-proBNP (> 857.5pg/ml)) indicated increased likelihood of SFTS progression into SVM., Conclusion: Elevated LDH, NT-proBNP, and consciousness disorders independently correlate with SFTS-SVM. LDH and NT-proBNP can aid in early identification of SFTS-SVM development when above specified thresholds., (© 2024. The Author(s).)

Severe fever with thrombocytopenia syndrome (SFTS) is a hemorrhagic fever caused by SFTS virus (SFTSV), which is primarily found in East Asian countries. Despite its high mortality rate and increasing incidence, no vaccines or therapeutics have yet been approved for use against SFTS. Antibody drugs have shown promise in treating lethal infectious diseases that currently have no established treatments. In the case of SFTS, however, only a limited amount of research has been done on SFTSV-neutralizing antibodies targeting the transmembrane proteins Gn and Gc, which play critical roles in viral infection. This study focuses on the production and characterization of antibodies targeting the SFTSV Gc protein. Monoclonal antibodies against Gc were generated through immunization of mice, and their antiviral activity was evaluated. Three out of four anti-Gc antibody clones from this study demonstrated dose-dependent SFTSV neutralization activity, two of which exhibited a synergistic effect on the neutralization activity of the anti-Gn antibody clone Mab4-5. Further studies are necessary to identify key sites on the SFTSV glycoprotein and to develop novel agents as well as antibodies with diverse mechanisms of action against SFTSV., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Competing Interests: Declaration of interests The author has no conflicts of interest.

Background: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging zoonosis with a high fatality rate in China. Previous studies have reported that dysregulated inflammatory response is associated with disease pathogenesis and mortality in patients with SFTS. This investigation aimed to evaluate the prevalence and characteristics of systemic inflammatory response syndrome (SIRS), and its impact on prognosis., Methods: Data on demographic characteristics, comorbid conditions, clinical manifestations, laboratory parameters, and survival time of patients with SFTS were collected. Patients were divided into the non-SIRS and SIRS groups according to the presence of SIRS, then their clinical data were compared., Results: A total of 290 patients diagnosed with SFTS were retrospectively enrolled, including 126(43.4%) patients with SIRS. Patients in the non-survivor group had more prevalence of SIRS than patients in the survivor group (P < 0.001), and SIRS (adjusted OR 2.885, 95% CI 1.226-6.786; P = 0.005) was shown as an independent risk factor for prognosis of patients with SFTS. Compared with patients without SIRS, patients with SIRS had lower WBC and neutrophils counts, and fibrinogen levels, but higher AST, LDH, amylase, lipase, CK, CK-MB, troponin I, APTT, thrombin time, D-dimer, CRP, IL-6, SAA levels, and viral load. The cumulative survival rate of patients with SIRS was significantly lower than that of patients without SIRS. Patients with SIRS also showed a higher incidence of bacterial or fungal infections than patients without SIRS., Conclusions: SIRS is highly frequent in patients with SFTS, and it is associated with high mortality., (© 2024. The Author(s).)

Objective: To understand the epidemiological characteristics and incidence trend of severe fever with thrombocytopenia syndrome (SFTS) in China. Methods: The incidence data of SFTS in China from 2018 to 2021 were collected from Chinese Disease Prevention and Control Information System for a statistical and descriptive epidemiological analysis by using software such as Excel 2016, Joinpoint 5.0.2, SPSS 26.0, and GraphPad Prism 8.0, especially, the SFTS cases reported monthly by key provinces were analyzed. Results: From 2018 to 2021, a total of 8 835 SFTS cases were reported in 25 provinces and the annual incidence showed an upward trend. The distribution of SFTS cases showed clustering, but the cases were mainly sporadic ones. The cases began to increase in March, mainly occurred during April to October (96.79%,8 551/8 835), and peaked during May to July. The cases were mainly distributed in middle-aged and old farmers, and slight more cases were women. The average case fatality rate was 5.38%, which varied greatly with areas. The case fatality rate tended to increase with age. Conclusion: From 2018 to 2021, the epidemiological characteristics of SFTS in China remained stable, but the number of reported cases gradually increased and the distribution showed an expanding trend, to which close attention should be paid.

Rift Valley fever is a zoonotic viral disease transmitted by mosquitoes, impacting both humans and livestock. Currently, there are no approved vaccines or antiviral treatments for humans. This study aimed to evaluate the in vitro efficacy of chemical compounds targeting the Gc fusion mechanism. These compounds were identified through virtual screening of millions of commercially available small molecules using a structure-based artificial intelligence bioactivity predictor. In our experiments, a pretreatment with small molecule compounds revealed that 3 out of 94 selected compounds effectively inhibited the replication of the Rift Valley fever virus MP-12 strain in Vero cells. As anticipated, these compounds did not impede viral RNA replication when administered three hours after infection. However, significant inhibition of viral RNA replication occurred upon viral entry when cells were pretreated with these small molecules. Furthermore, these compounds exhibited significant inhibition against Arumowot virus, another phlebovirus, while showing no antiviral effects on tick-borne bandaviruses. Our study validates AI-based virtual high throughput screening as a rational approach for identifying effective antiviral candidates for Rift Valley fever virus and other bunyaviruses.

Rift Valley fever virus (RVFV) is a pathogen transmitted to humans and livestock via mosquito bites. This virus, which was discovered in Kenya in 1930, is considered by the World Health Organization (WHO) and the World Organisation for Animal Health (WOAH) to be associated with a high risk of causing large-scale epidemics. However, means dedicated to fighting RVFV have been limited, and despite recent research efforts, the virus remains poorly understood at both the molecular and cellular levels as well as at a broader scale of research in the field and in animal and human populations. In this introductory chapter of a methods book, we aim to provide readers with a concise overview of RVFV, from its ecology and transmission to the structural and genomic organization of virions and its life cycle in host cells., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Single-domain antibodies, referred to as VHH (variable heavy chains of heavy chain-only antibodies) or in their commercial name as nanobodies, are potent tools for the detection of target proteins in biological samples. They have the advantage of being highly stable, specific, and sensitive, with affinities reaching the nanomolar range. We utilized this tool to develop a rapid detection method that discriminates cells infected with Rift Valley fever virus (RVFV), based on the intracellular detection of the viral nonstructural NSm protein localized on the outer membrane of mitochondria. Here we describe how NSm-specific VHHs have been produced, cloned, and characterized, highlighting their value in RVFV research and diagnosis. This work may also raise interest in other potential applications such as antiviral therapy., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Rift Valley fever virus (RVFV) is a mosquito-borne pathogen that represents a significant threat to both human and veterinary public health. Since its discovery in the Great Rift Valley of Kenya in the 1930s, the virus has spread across Africa and beyond, now posing a risk of introduction into Southern Europe and Asia. Despite recent progresses, early RVFV-host cell interactions remain largely uncharacterized. In this method chapter, we delineate the procedure for labeling RVFV particles with fluorescent organic dyes. This approach makes it feasible to visualize single viral particles in both fixed and living cells and study RVFV entry into host cells. We provide additional examples with two viruses closely related to RVFV, namely, Toscana virus and Uukuniemi virus. Furthermore, we illustrate how to utilize fluorescent viral particles to examine and quantify each step of the cell entry program of RVFV, which includes state-of-the-art fluorescence-based detection techniques such as fluorescence microscopy, flow cytometry, and fluorimetry., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Sandfly-borne phleboviruses (phylum Negarnavaricota, realm Riboviria, kingdom Orthornavirae, genus Phlebovirus) comprise three genome segments of ribonucleic acid (RNA) and which encode an RNA-dependent RNA polymerase, which they use to transcribe the viral RNA genome into messenger RNA and to replicate the genome. At least some of these viruses cause mild 3-day fevers in humans but some also have been associated with more severe illnesses in humans. The 67 recognized phleboviruses are listed here in a table composed by the authors from International Committee on Taxonomy of Viruses reports as well as the scientific literature.