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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 -
The Journal of General Virology Aug 2019Rift Valley fever (RVF) is a mosquito-borne viral zoonosis that was first discovered in Kenya in 1930 and is now endemic throughout multiple African countries and the... (Review)
Review
Rift Valley fever (RVF) is a mosquito-borne viral zoonosis that was first discovered in Kenya in 1930 and is now endemic throughout multiple African countries and the Arabian Peninsula. RVF virus primarily infects domestic livestock (sheep, goats, cattle) causing high rates of neonatal mortality and abortion, with human infection resulting in a wide variety of clinical outcomes, ranging from self-limiting febrile illness to life-threatening haemorrhagic diatheses, and miscarriage in pregnant women. Since its discovery, RVF has caused many outbreaks in Africa and the Arabian Peninsula with major impacts on human and animal health. However, options for the control of RVF outbreaks are limited by the lack of licensed human vaccines or therapeutics. For this reason, RVF is prioritized by the World Health Organization for urgent research and development of countermeasures for the prevention and control of future outbreaks. In this review, we highlight the current understanding of RVF, including its epidemiology, pathogenesis, clinical manifestations and status of vaccine development.
Topics: Animals; Humans; Rift Valley Fever; Rift Valley fever virus; Zoonoses
PubMed: 31310198
DOI: 10.1099/jgv.0.001296 -
Frontiers in Immunology 2022Severe fever with thrombocytopenia syndrome (SFTS), which is caused by SFTS virus (SFTSV), poses a serious threat to global public health, with high fatalities and an... (Review)
Review
Severe fever with thrombocytopenia syndrome (SFTS), which is caused by SFTS virus (SFTSV), poses a serious threat to global public health, with high fatalities and an increasing prevalence. As effective therapies and prevention strategies are limited, there is an urgent need to elucidate the pathogenesis of SFTS. SFTSV has evolved several mechanisms to escape from host immunity. In this review, we summarize the mechanisms through which SFTSV escapes host immune responses, including the inhibition of innate immunity and evasion of adaptive immunity. Understanding the pathogenesis of SFTS will aid in the development of new strategies for the treatment of this disease.
Topics: Bunyaviridae Infections; Humans; Immunity, Innate; Phlebovirus; Severe Fever with Thrombocytopenia Syndrome
PubMed: 35967309
DOI: 10.3389/fimmu.2022.937684 -
International Journal of Molecular... Sep 2022Severe fever with thrombocytopenia syndrome (SFTS) has been acknowledged as an emerging infectious disease that is caused by the SFTS virus (SFTSV). The main clinical... (Review)
Review
Severe fever with thrombocytopenia syndrome (SFTS) has been acknowledged as an emerging infectious disease that is caused by the SFTS virus (SFTSV). The main clinical features of SFTS on presentation include fever, thrombocytopenia, leukocytopenia and gastrointestinal symptoms. The mortality rate is estimated to range between 5‑30% in East Asia. However, SFTSV infection is increasing on an annual basis globally and is becoming a public health problem. The transmission cycle of SFTSV remains poorly understood, which is compounded by the pathogenesis of SFTS not being fully elucidated. Since the mechanism underlying the host immune response towards SFTSV is also unclear, there are no effective vaccines or specific therapeutic agents against SFTS, with supportive care being the only realistic option. Therefore, it is now crucial to understand all aspects of the host‑virus interaction following SFTSV infection, including the antiviral states and viral evasion mechanisms. In the present review, recent research progress into the possible host immune responses against SFTSV was summarized, which may be useful in designing novel therapeutics against SFTS.
Topics: Bunyaviridae Infections; Humans; Phlebovirus; Severe Fever with Thrombocytopenia Syndrome; Thrombocytopenia
PubMed: 35856413
DOI: 10.3892/ijmm.2022.5174 -
Autophagy Jul 2022Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging negatively stranded enveloped RNA bunyavirus that causes SFTS with a high case fatality rate of...
Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging negatively stranded enveloped RNA bunyavirus that causes SFTS with a high case fatality rate of up to 30%. Macroautophagy/autophagy is an evolutionarily conserved process involved in the maintenance of host homeostasis, which exhibits anti-viral or pro-viral responses in reaction to different viral challenges. However, the interaction between the bunyavirus SFTSV and the autophagic process is still largely unclear. By establishing various autophagy-deficient cell lines, we found that SFTSV triggered RB1CC1/FIP200-BECN1-ATG5-dependent classical autophagy flux. SFTSV nucleoprotein induced BECN1-dependent autophagy by disrupting the BECN1-BCL2 association. Importantly, SFTSV utilized autophagy for the viral life cycle, which not only assembled in autophagosomes derived from the ERGIC and Golgi complex, but also utilized autophagic vesicles for exocytosis. Taken together, our results suggest a novel virus-autophagy interaction model in which bunyavirus SFTSV induces classical autophagy flux for viral assembly and egress processes, suggesting that autophagy inhibition may be a novel therapy for treating or releasing SFTS.
Topics: Autophagy; Humans; Orthobunyavirus; Phlebovirus; Severe Fever with Thrombocytopenia Syndrome; Virus Assembly
PubMed: 34747299
DOI: 10.1080/15548627.2021.1994296 -
Emerging Microbes & Infections Dec 2022Severe fever with thrombocytopenia syndrome virus (SFTSV), an emerging tick-borne bunyavirus, causes mild-to-moderate infection to critical illness or even death in...
Severe fever with thrombocytopenia syndrome virus (SFTSV), an emerging tick-borne bunyavirus, causes mild-to-moderate infection to critical illness or even death in human patients. The effect of virus variations on virulence and related clinical significance is unclear. We prospectively recruited SFTSV-infected patients in a hotspot region of SFTS endemic in China from 2011 to 2020, sequenced whole genome of SFTSV, and assessed the association of virus genomic variants with clinical data, viremia, and inflammatory response. We identified seven viral clades (I-VII) based on phylogenetic characterization of 805 SFTSV genome sequences. A significantly increased case fatality rate (32.9%) was revealed in one unique clade (IV) that possesses a specific co-mutation pattern, compared to other three common clades (I, 16.7%; II, 13.8%; and III, 11.8%). The phenotype-genotype association (hazard ratios ranged 1.327-2.916) was confirmed by multivariate regression adjusting age, sex, and hospitalization delay. We revealed a pronounced inflammation response featured by more production of CXCL9, IL-10, IL-6, IP-10, M-CSF, and IL-1β, in clade IV, which was also related to severe complications. We observed enhanced cytokine expression from clade IV inoculated PBMCs and infected mice. Moreover, the neutralization activity of convalescent serum from patients infected with one specified clade was remarkably reduced to other viral clades. Together, our findings revealed a significant association between one specific viral clade and SFTS fatality, highlighting the need for molecular surveillance for highly lethal strains in endemic regions and unravelled the importance of evaluating cross-clade effect in development of vaccines and therapeutics.
Topics: Animals; Bunyaviridae Infections; Genomics; Humans; Mice; Phlebovirus; Phylogeny; Severe Fever with Thrombocytopenia Syndrome
PubMed: 35603493
DOI: 10.1080/22221751.2022.2081617 -
Current Opinion in Virology Oct 2021Hantaviruses are rodent-borne viruses distributed worldwide, transmitted through the air and with the ability to spread from person to person. They maintain a... (Review)
Review
Hantaviruses are rodent-borne viruses distributed worldwide, transmitted through the air and with the ability to spread from person to person. They maintain a non-symptomatic persistent infection in their rodent hosts, but their spillover to humans produces a renal or pulmonary syndrome associated with high fatality rates. Hantavirus particles are lipid-enveloped and display a characteristic surface lattice built up of tetragonal spikes composed of two glycoproteins, Gn and Gc. The pleomorphism of these particles has hindered cryo-EM efforts to obtain detailed structural information and only by using a combination of X-ray crystallography and cryo-electron tomography it was possible to build an atomic model of the surface lattice. Here we review these structural efforts and the unanticipated evolutionary relations between hantaviruses and alphaviruses highlighted by these studies.
Topics: Glycoproteins; Orthohantavirus; Hantavirus Infections; Humans; Membrane Glycoproteins; RNA Viruses
PubMed: 34418649
DOI: 10.1016/j.coviro.2021.07.009 -
Viruses May 2021Negative-strand (-) RNA viruses (NSVs) comprise a large and diverse group of viruses that are generally divided in those with non-segmented and those with segmented... (Review)
Review
Negative-strand (-) RNA viruses (NSVs) comprise a large and diverse group of viruses that are generally divided in those with non-segmented and those with segmented genomes. Whereas most NSVs infect animals and humans, the smaller group of the plant-infecting counterparts is expanding, with many causing devastating diseases worldwide, affecting a large number of major bulk and high-value food crops. In 2018, the taxonomy of segmented NSVs faced a major reorganization with the establishment of the order . This article overviews the major plant viruses that are part of the order, i.e., orthospoviruses (), tenuiviruses (), and emaraviruses (), and provides updates on the more recent ongoing research. Features shared with the animal-infecting counterparts are mentioned, however, special attention is given to their adaptation to plant hosts and vector transmission, including intra/intercellular trafficking and viral counter defense to antiviral RNAi.
Topics: Bunyaviridae; Plant Diseases; Plant Viruses; Plants; RNA Viruses
PubMed: 34066457
DOI: 10.3390/v13050842 -
Cell Research Feb 2024Crimean-Congo hemorrhagic fever virus (CCHFV) is the most widespread tick-born zoonotic bunyavirus that causes severe hemorrhagic fever and death in humans. CCHFV enters...
Crimean-Congo hemorrhagic fever virus (CCHFV) is the most widespread tick-born zoonotic bunyavirus that causes severe hemorrhagic fever and death in humans. CCHFV enters the cell via clathrin-mediated endocytosis which is dependent on its surface glycoproteins. However, the cellular receptors that are required for CCHFV entry are unknown. Here we show that the low density lipoprotein receptor (LDLR) is an entry receptor for CCHFV. Genetic knockout of LDLR impairs viral infection in various CCHFV-susceptible human, monkey and mouse cells, which is restored upon reconstitution with ectopically-expressed LDLR. Mutagenesis studies indicate that the ligand binding domain (LBD) of LDLR is necessary for CCHFV infection. LDLR binds directly to CCHFV glycoprotein Gc with high affinity, which supports virus attachment and internalization into host cells. Consistently, a soluble sLDLR-Fc fusion protein or anti-LDLR blocking antibodies impair CCHFV infection into various susceptible cells. Furthermore, genetic knockout of LDLR or administration of an LDLR blocking antibody significantly reduces viral loads, pathological effects and death following CCHFV infection in mice. Our findings suggest that LDLR is an entry receptor for CCHFV and pharmacological targeting of LDLR may provide a strategy to prevent and treat Crimean-Congo hemorrhagic fever.
Topics: Animals; Humans; Mice; Endocytosis; Glycoproteins; Hemorrhagic Fever Virus, Crimean-Congo; Hemorrhagic Fever, Crimean; Receptors, LDL; Virus Internalization
PubMed: 38182887
DOI: 10.1038/s41422-023-00917-w -
Antiviral Research Mar 2022Human infection with Crimean-Congo hemorrhagic fever virus (CCHFV), a tick-borne pathogen in the family Nairoviridae, can result in a spectrum of outcomes, ranging from... (Review)
Review
Human infection with Crimean-Congo hemorrhagic fever virus (CCHFV), a tick-borne pathogen in the family Nairoviridae, can result in a spectrum of outcomes, ranging from asymptomatic infection through mild clinical signs to severe or fatal disease. Studies of CCHFV immunobiology have investigated the relationship between innate and adaptive immune responses with disease severity, attempting to elucidate factors associated with differential outcomes. In this article, we begin by highlighting unanswered questions, then review current efforts to answer them. We discuss in detail current clinical studies and research in laboratory animals on CCHF, including immune targets of infection and adaptive and innate immune responses. We summarize data about the role of the immune response in natural infections of animals and humans and experimental studies in vitro and in vivo and from evaluating immune-based therapies and vaccines, and present recommendations for future research.
Topics: Animals; Hemorrhagic Fever Virus, Crimean-Congo; Hemorrhagic Fever, Crimean; Ticks
PubMed: 35026307
DOI: 10.1016/j.antiviral.2022.105244