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One Health (Amsterdam, Netherlands) Dec 2023High seroprevalence rates of several phleboviruses have been reported in domestic animals and humans in sandfly-infested regions. Sandfly Fever Sicilian virus (SFSV) and...
High seroprevalence rates of several phleboviruses have been reported in domestic animals and humans in sandfly-infested regions. Sandfly Fever Sicilian virus (SFSV) and Toscana virus (TOSV) are two of these viruses commonly transmitted by sandflies. While SFSV can cause rapidly resolving mild febrile illness, TOSV could involve the central nervous system (CNS), causing diseases ranging from aseptic meningitis to meningoencephalitis. Sandfly-associated phleboviruses have not been investigated before in Saudi Arabia and are potential causes of infection given the prevalence of sandflies in the country. Here, we investigated the seroprevalence of SFSV and TOSV in the western region of Saudi Arabia in samples collected from blood donors, livestock animals, and animal handlers. An overall seroprevalence of 9.4% and 0.8% was found in humans for SFSV and TOSV, respectively. Seropositivity was significantly higher in non-Saudis compared to Saudis and increased significantly with age especially for SFSV. The highest seropositivity rate was among samples collected from animal handlers. Specifically, in blood donors, 6.4% and 0.7% tested positive for SFSV and TOSV nAbs, respectively. Animal handlers showed higher seroprevalence rates of 16% and 1% for anti-SFSV and anti-TOSV nAbs, respectively, suggesting that contact with livestock animals could be a risk factor. Indeed, sera from livestock animals showed seropositivity of 53.3% and 4.4% in cows, 27.5% and 7.8% in sheep, 2.2% and 0.0% in goats, and 10.0% and 2.3% in camels for SFSV and TOSV, respectively. Together, these results suggest that both SFSV and TOSV are circulating in the western region of Saudi Arabia in humans and livestock animals, albeit at different rates, and that age and contact with livestock animals could represent risk factors for infection with these viruses.
PubMed: 37520847
DOI: 10.1016/j.onehlt.2023.100601 -
The Journal of Infectious Diseases Oct 2023Research directed at select prototype pathogens is part of the approach put forth by the National Institute of Allergy and Infectious Disease (NIAID) to prepare for...
Research directed at select prototype pathogens is part of the approach put forth by the National Institute of Allergy and Infectious Disease (NIAID) to prepare for future pandemics caused by emerging viruses. We were tasked with identifying suitable prototypes for four virus families of the Bunyavirales order (Phenuiviridae, Peribunyaviridae, Nairoviridae, and Hantaviridae). This is a challenge due to the breadth and diversity of these viral groups. While there are many differences among the Bunyavirales, they generally have complex ecological life cycles, segmented genomes, and cause a range of human clinical outcomes from mild to severe and even death. Here, we delineate potential prototype species that encompass the breadth of clinical outcomes of a given family, have existing reverse genetics tools or animal disease models, and can be amenable to a platform approach to vaccine testing. Suggested prototype pathogens outlined here can serve as a starting point for further discussions.
Topics: Animals; Humans; RNA Viruses
PubMed: 37849397
DOI: 10.1093/infdis/jiac338 -
Science Progress 2024The common gastrointestinal commensal is a mucin-degrading bacterium that is greatly reduced in individuals consuming a high-fat diet. Increasing evidence from a...
The common gastrointestinal commensal is a mucin-degrading bacterium that is greatly reduced in individuals consuming a high-fat diet. Increasing evidence from a variety of clinical and pre-clinical studies suggests that oral supplementation with can improve metabolic health and moderate systemic inflammation. We and others have demonstrated a role for administration in protection against infectious disease and the outcome from sepsis. Very recent studies have indicated the molecular mechanisms by which may interact with the host to influence systemic immune-regulation and control of microbial pathogenesis. Here we consider recent studies which demonstrate the efficacy of this potential next-generation probiotic in animal models of Typhimurium, and as well as influenza virus and phlebovirus. The potential mechanisms by which may influence local and systemic immune responses are discussed.
Topics: Animals; Humans; Verrucomicrobia; Akkermansia; Probiotics; Communicable Diseases
PubMed: 38490164
DOI: 10.1177/00368504241231159 -
Ticks and Tick-borne Diseases Jan 2024Severe fever with thrombocytopenia syndrome (SFTS) is a newly emerged tick-borne viral zoonosis and widely prevalent in China, Japan and South Korea. Most reported SFTS...
Severe fever with thrombocytopenia syndrome (SFTS) is a newly emerged tick-borne viral zoonosis and widely prevalent in China, Japan and South Korea. Most reported SFTS cases have been identified in mountainous and hilly areas, with a few in island areas. In this study, we conducted a systematic investigation about natural infection of SFTS virus (SFTSV) among humans, animals and ticks in a coastal endemic prefecture, containing island, plains and mountain settings, in Zhejiang Province, Southeastern China. From July 2020 to June 2021, 1117 participants completed a survey with questionnaire interview and serum testing. Meanwhile, 862 serum samples of domestic animals, 275 spleen tissue samples of wild animals and 829 ticks representing five species (predominantly Haemaphysalis longicornis and Rhipicephalus sanguineus sensu lato) were collected. The seroprevalence of anti-SFTSV total antibody and IgM antibody among the participants was 4.8 % (54/1117) and 0.6 % (7/1117), respectively. Multivariate logistic regression analysis indicated that living in the island area (OR=2.66; 95 %CI: 1.04-6.80; P = 0.041) was significantly associated with seropositivity of total antibody to SFTSV. Furthermore, a higher seroprevalence was observed in domestic animals (36.1 %), while the SFTSV-RNA infection rate was 0.4 % in wild animals and the minimum infection rate (MIR) was 0.8 % for all tick species combined. The only tick species infected with SFTSV was H. longicornis. The prevalence of SFTSV infection in the island area, manifested by anti-SFTSV total antibody (P = 0.012) and IgM antibody (P = 0.004) among humans, anti-SFTSV total antibody (P<0.001) among domestic animals, and SFTSV-RNA among ticks (P = 0.022), was significantly higher than that in the mountainous area and the plain area. Furthermore, phylogenetic analysis showed that SFTSV sequences obtained from ticks in the island area were clustered with reported strains in Japan and South Korea. These results suggest that islands in the study area might be an important natural focus of SFTSV.
Topics: Animals; Humans; Severe Fever with Thrombocytopenia Syndrome; Phylogeny; Seroepidemiologic Studies; Phlebovirus; Animals, Domestic; Animals, Wild; China; RNA; Rhipicephalus sanguineus; Immunoglobulin M; Bunyaviridae Infections
PubMed: 37981467
DOI: 10.1016/j.ttbdis.2023.102277 -
Emerging Infectious Diseases Sep 2023A new phlebovirus variant was isolated from an acute febrile patient in Chanchamayo, Peru. Genome characterization and p-distance analyses based on complete open reading...
A new phlebovirus variant was isolated from an acute febrile patient in Chanchamayo, Peru. Genome characterization and p-distance analyses based on complete open reading frames revealed that the virus is probably a natural reassortant of the Echarate virus (large and small segments) with a yet-unidentified phlebovirus (M segment).
Topics: Humans; Peru; Fever; Open Reading Frames; Phlebovirus
PubMed: 37610254
DOI: 10.3201/eid2909.230374 -
Proceedings of the National Academy of... Jun 2024Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with a high fatality rate of up to 30% caused by SFTS virus (SFTSV). However, no...
Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with a high fatality rate of up to 30% caused by SFTS virus (SFTSV). However, no specific vaccine or antiviral therapy has been approved for clinical use. To develop an effective treatment, we isolated a panel of human monoclonal antibodies (mAbs). SF5 and SF83 are two neutralizing mAbs that recognize two viral glycoproteins (Gn and Gc), respectively. We found that their epitopes are closely located, and we then engineered them as several bispecific antibodies (bsAbs). Neutralization and animal experiments indicated that bsAbs display more potent protective effects than the parental mAbs, and the cryoelectron microscopy structure of a bsAb3 Fab-Gn-Gc complex elucidated the mechanism of protection. In vivo virus passage in the presence of antibodies indicated that two bsAbs resulted in less selective pressure and could efficiently bind to all single parental mAb-escape mutants. Furthermore, epitope analysis of the protective mAbs against SFTSV and RVFV indicated that they are all located on the Gn subdomain I, where may be the hot spots in the phleboviruses. Collectively, these data provide potential therapeutic agents and molecular basis for the rational design of vaccines against SFTSV infection.
Topics: Animals; Antibodies, Bispecific; Mice; Antibodies, Neutralizing; Phlebovirus; Humans; Antibodies, Viral; Glycoproteins; Antibodies, Monoclonal; Epitopes; Disease Models, Animal; Severe Fever with Thrombocytopenia Syndrome
PubMed: 38830098
DOI: 10.1073/pnas.2400163121 -
Brazilian Journal of Microbiology :... Sep 2023Belonging to genus Bandavirus in Phenuiviridae family, Guertu bandavirus (GTV) is a potential pathogen closely related to severe fever with thrombocytopenia syndrome...
Developing and characterizing monoclonal antibodies of Guertu bandavirus nucleoprotein for developing methods of Guertu bandavirus and severe fever with thrombocytopenia syndrome virus detection.
Belonging to genus Bandavirus in Phenuiviridae family, Guertu bandavirus (GTV) is a potential pathogen closely related to severe fever with thrombocytopenia syndrome virus (SFTSV) and heartland virus (HRTV) associated with human diseases. Although the medical significance of GTV is not clear, there was serological evidence suggesting past infection with this virus has occurred, indicating its potential threat to human health. So, it is important to prepare for detection of GTV infection so as to control virus transmission and promote disease diagnosis and treatment. This study is aimed at obtaining monoclonal antibodies (mAbs) against GTV nucleoprotein (NP) and evaluating their activities in recognizing viral antigens from genetic-related bandaviruses, SFTSV and HRTV. Eight mAbs were obtained and four of them (22G1, 25C2, 25E2, and 26F8) recognize linear epitopes of GTV NP. The four mAbs showed cross-reactivity to SFTSV but were unable to react with HRTV. Two fine epitopes were identified by the four mAbs, E1 (YNSFRDPLHAAV) and E2 (GPDGLP), which are highly conserved in the NPs of GTV and SFTSV but are distinct in HRTV NP. The features of epitopes, including their hydrophilicity, antibody accessibility, flexibility, antigenicity, and spatial locations, were predicted and analyzed, and their potential functional impacts on virus infection and replication and their use for virus detection were discussed. Our results promote the understanding of the molecular basis of GTV and SFTSV NP in inducing antibody responses. The NP-specific mAbs generated in this study are promising fundamental materials for developing viral antigen detection methods for GTV and SFTSV.
Topics: Humans; Severe Fever with Thrombocytopenia Syndrome; Antibodies, Monoclonal; Nucleoproteins; Phlebovirus; RNA Viruses; Epitopes
PubMed: 37225938
DOI: 10.1007/s42770-023-00982-8 -
Journal of Virology Sep 2023Rift Valley fever virus (RVFV) causes mild to severe disease in humans and livestock. Outbreaks of RVFV have been reported throughout Africa and have spread outside...
Rift Valley fever virus (RVFV) causes mild to severe disease in humans and livestock. Outbreaks of RVFV have been reported throughout Africa and have spread outside Africa since 2000, calling for urgent worldwide attention to this emerging virus. RVFV directly infects the liver, and elevated transaminases are a hallmark of severe RVFV infection. However, the specific contribution of viral replication in hepatocytes to pathogenesis of RVFV remains undefined. To address this, we generated a recombinant miRNA-targeted virus, RVFVmiR-122, to limit hepatocellular replication. MicroRNAs are evolutionarily conserved non-coding RNAs that regulate mRNA expression by targeting them for degradation. RVFVmiR-122 includes an insertion of four target sequences of the liver-specific miR-122. In contrast to control RVFVmiR-184, which contains four target sequences of mosquito-specific miR-184, RVFVmiR-122 has restricted replication in primary mouse hepatocytes. RVFVmiR-122-infected C57BL/6 mice survived acute hepatitis and instead developed late-onset encephalitis. This difference in clinical outcome was eliminated in mice, confirming the specificity of the finding. Interestingly, C57BL/6 mice infected with higher doses of RVFVmiR-122 had a higher survival rate which was correlated with faster clearance of virus from the liver, suggesting a role for activation of host immunity in the phenotype. Together, our data demonstrate that miR-122 can specifically restrict the replication of RVFVmiR-122 in liver tissue both and , and this restriction alters the clinical course of disease following RVFVmiR-122 infection. IMPORTANCE Rift Valley fever virus (RVFV) is a hemorrhagic fever virus that causes outbreaks in humans and livestock throughout Africa and has spread to continents outside Africa since 2000. However, no commercial vaccine or treatment is currently available for human use against RVFV. Although the liver has been demonstrated as a key target of RVFV, the contribution of viral replication in hepatocytes to overall RVFV pathogenesis is less well defined. In this study we addressed this question by using a recombinant miRNA-targeted virus with restricted replication in hepatocytes. We gained a better understanding of how this individual cell type contributes to the development of disease caused by RVFV. Techniques used in this study provide an innovative tool to the RVFV field that could be applied to study the consequences of limited RVFV replication in other target cells.
Topics: Animals; Humans; Mice; Hepatocytes; Mice, Inbred C57BL; MicroRNAs; Rift Valley Fever; Rift Valley fever virus; Virus Replication
PubMed: 37695055
DOI: 10.1128/jvi.00853-23 -
Emerging Microbes & Infections Dec 2024Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease with an increasing annual incidence rate. In this case report, we presented two...
Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease with an increasing annual incidence rate. In this case report, we presented two patients infected with the SFTS virus, suggesting a potential direct transmission route from camels to humans through blood contact. Both patients developed symptoms after engaging in the slaughtering of one sick camel, while their family members living in the same environment or co-diners remained unaffected. Subsequent detection revealed a high viral load of SFTS virus, reaching 10 viral RNA copies/ml, in the sample obtained from the sick camel. Metagenomic sequencing did not identify any other pathogens. The SFTS virus was successfully isolated from both patient and camel samples. The complete nucleotide sequences obtained from the infected patients demonstrated a remarkable 100% similarity to those found in the camel, and genetic evolution analysis classified the virus as genotype A. Additionally, partial sequences of the SFTS virus were identified in ticks captured from the camel rearing environment, however, these sequences showed only 95.9% similarity to those found in camel and humans. Furthermore, immunoglobulin M and immunoglobulin G antibodies were detected in serum samples collected from the patient. Our findings provide evidence that camel may serve as a competent reservoir for transmitting the SFTS virus to humans. Further investigations into SFTS virus infections in large animals are warranted to understand their role in viral maintenance and transmission.
Topics: Animals; Humans; Camelus; China; Immunoglobulin G; Phlebovirus; Severe Fever with Thrombocytopenia Syndrome
PubMed: 38269573
DOI: 10.1080/22221751.2024.2309990 -
Biomedicines Feb 2024Rift Valley fever is a vector-borne zoonotic disease caused by the Rift Valley fever virus (Phlebovirus genus) listed among the eight pathogens included in the Bluepoint... (Review)
Review
Rift Valley fever is a vector-borne zoonotic disease caused by the Rift Valley fever virus (Phlebovirus genus) listed among the eight pathogens included in the Bluepoint list by the WHO. The transmission is mainly vehicled by and mosquito species. Symptoms of the disease are varied and non-specific, making clinical diagnosis often challenging, especially in the early stages. Due to the difficulty in distinguishing Rift Valley fever from other viral hemorrhagic fevers, as well as many other diseases that cause fever, an early diagnosis of the infection is important to limit its spread and to provide appropriate care to patients. To date, there is no validated point-of-care diagnostic tool. The virus can only be detected in the blood for a brief period, suggesting that molecular methods alone are not sufficient for case determination. For this, it is preferable to combine both molecular and serological tests. The wide distribution of competent vectors in non-endemic areas, together with global climate change, elicit the spread of RVFV to continents other than Africa, making surveillance activities vital to prevent or to limit the impact of human outbreaks and for a rapid identification of positive cases, making diagnosis a key factor for this achievement.
PubMed: 38540153
DOI: 10.3390/biomedicines12030540