RESUMO
A wide variety of infections can trigger cytokine storm syndromes including those caused by bacteria, viruses, fungi and parasites. The most frequent viral trigger is Epstein-.Barr virus which is covered in Chapter 16. CSS associated with COVID-19 is also discussed separately (Chapter 22). This chapter will focus on other viruses including the hemorrhagic fever viruses, influenza, parainfluenza, adenovirus, parvovirus, hepatitis viruses, measles, mumps, rubella, enterovirus, parechovirus, rotavirus, human metapneumovirus and human T-lymphotropic virus. The published literature consists of many single case reports and moderate-sized case series reporting CSS, in most circumstances meeting the 2004 diagnostic criteria for hemophagocytic lymphohistiocytosis (HLH). There is no published clinical trial evidence specifically for management of HLH associated with these viruses. In some situations, patients received supportive therapy and blood product transfusions only but in most cases, they were treated with one or more of intravenous corticosteroids, intravenous immunoglobulin and/or etoposide. These were successful in many patients although in significant numbers progression of infection to CSS was associated with mortality.
Assuntos
COVID-19 , Síndrome da Liberação de Citocina , Humanos , Síndrome da Liberação de Citocina/imunologia , COVID-19/complicações , COVID-19/imunologia , COVID-19/terapia , COVID-19/virologia , Linfo-Histiocitose Hemofagocítica/terapia , Linfo-Histiocitose Hemofagocítica/imunologia , Linfo-Histiocitose Hemofagocítica/virologia , SARS-CoV-2 , Febres Hemorrágicas Virais/virologiaRESUMO
Introduction: Several arboviral diseases have been known to be endemic (e.g., Crimean-Congo hemorrhagic fever, Rift Valley fever) or are emerging (dengue fever, chikungunya, O'nyong-nyong) in human populations in Mauritania, while others have become rare in recent years (e.g. yellow fever). Moreover, domestic animals, especially cattle, camels, goats, and sheep, are also known to be infected with some of these arboviruses (e.g. Crimean-Congo hemorrhagic fever, Rift Valley fever). For these reasons, viral hemorrhagic fever surveillance in Mauritania is part of the Integrated Disease Surveillance and Response (IDSR). However, limited information is available on the efficacy of the viral hemorrhagic fever surveillance system in the Assaba region of Mauritania. The aim of the present study was to assess the performance of the surveillance system, in particular its general utility, simplicity, flexibility, acceptability, and reactivity. Methods: A descriptive cross-sectional study was conducted from July to August 2022 in the Assaba region with the objective of evaluating the characteristics of the system by interviewing key actors involved in the surveillance of viral hemorrhagic fevers, with a focus on Rift Valley fever and Crimean-Congo hemorrhagic fever, using questionnaires developed following the guidelines of the Centers for Disease Control and Prevention (Atlanta, Georgia, USA). Data from 2020-2022 on viral hemorrhagic fevers from the National Institute of Public Health laboratory were analyzed. Medians, interquartile ranges, and proportions were calculated using Epi Info® 7.2.5.0 and Excel® 2021. Results: The questionnaire was answered by all twenty-six persons involved in the viral hemorrhagic fever surveillance system in Assaba region. The majority of survey respondents found the system to be useful (51%), simple (63%), acceptable (46%), responsive (64%), and flexible (46%). An analysis of the data revealed a positive predictive value of 28% for Rift Valley Fever. The weekly distribution of cases within the wilaya indicates that the moughataa of Kiffa recorded the highest number of cases in September, with a notable weekly peak during that month in 2020. According to the analysis of the National Institute of Public Health database, cases of viral hemorrhagic fevers were promptly handled. Survey responses and database analysis revealed issues related to data quality and data management mechanisms. These limitations in the surveillance system are likely to be due to insufficient resources and training of the personnel, in particular with regards to data collection and management, which in turn led to incomplete or missing data and invalid data entry. These weak points can be ascribed, at least in part, to financial constraints and inadequate attribution of priority to arboviral diseases. Despite these limitations, disease data generated by the surveillance system were generally reliable. Conclusion: The viral hemorrhagic fever surveillance system in the Assaba region adheres to the organization and functioning of the national viral hemorrhagic fever surveillance system, which is part of the IDSR. The characteristics of utility, simplicity, responsiveness, and flexibility of the viral hemorrhagic fever surveillance system are good, but acceptability and flexibility need further improvement. The earlier the first arboviral human or animal cases are detected, the more likely an active intervention can be organized in response to the emerging epidemic or epizootic and prevent the spread of the disease. An efficient viral surveillance system is the key to reducing the negative impact of arboviral diseases in Assaba region.
Assuntos
Febres Hemorrágicas Virais , Mauritânia/epidemiologia , Humanos , Estudos Transversais , Febres Hemorrágicas Virais/epidemiologia , Febres Hemorrágicas Virais/virologia , Vigilância da População/métodos , AnimaisRESUMO
There have been several Viral Hemorrhagic Fever (VHF) outbreaks in Nigeria which remains a public health concern. Despite the increasing number of suspected cases of VHF due to heightened surveillance activities and growing awareness, only a few cases are laboratory-confirmed to be VHF. Routinely, these samples are only tested for Lassa virus and Yellow fever virus with occasional testing for Dengue virus when indicated. The aetiology of the disease in these VHF suspected cases in Nigeria which are negative for Lassa, Yellow fever and Dengue viruses remains a puzzle. Since the clinical features exhibited by suspected VHF cases are like other endemic illnesses such as Hepatitis, there is a need to investigate the diversity and co-infections of hepatitis viruses as differentials and possible co-morbidity in suspected cases of VHFs in Nigeria. A total of three hundred and fifty (350) blood samples of 212 (60.6%) males and 138 (39.4%) females, aged <1-70 years with a mean age of 25 ±14.5, suspected of VHFs and tested negative for Lassa, Yellow fever and Dengue viruses were investigated for Hepatitis A, B, C and E viruses at the Centre for Human and Zoonotic Virology (CHAZVY), College of Medicine, University of Lagos (CMUL) using serologic and molecular techniques. The serologic analysis of these VHF suspected cases samples revealed that 126 (36%) were positive for at least one hepatitis virus. Individual prevalence for each of the hepatitis virus screened for showed that 37 (10.6%), 18 (5.1%) and 71 (20.3%) were positive for HBV, HCV and HEV respectively. All the samples were negative for HAV. A co-infection rate of 11.9% was also observed, with HCV/HEV co-infections being the most prevalent and the Northern region having the greatest burden of infection. The evidence of hepatitis virus infections in suspected cases of VHF was documented. Thus, their associations as co-morbidities and/or mortalities in this category of individuals require further investigations in endemic countries such as Nigeria. Therefore, the possible inclusion of screening for hepatitis viruses and other aetiologic agents that could mimic infections in suspected cases of VHFs in Nigeria should be thoroughly evaluated to guide informed policy on the diagnosis and management of these cases.
Assuntos
Febres Hemorrágicas Virais , Humanos , Nigéria/epidemiologia , Masculino , Feminino , Adulto , Adolescente , Pessoa de Meia-Idade , Febres Hemorrágicas Virais/epidemiologia , Febres Hemorrágicas Virais/diagnóstico , Febres Hemorrágicas Virais/virologia , Criança , Idoso , Pré-Escolar , Adulto Jovem , Lactente , Vírus de Hepatite/isolamento & purificação , Coinfecção/epidemiologia , Coinfecção/virologiaRESUMO
The hemorrhagic fever viruses (HFVs) cause severe or fatal infections in humans. Named after their common symptom hemorrhage, these viruses induce significant vascular dysfunction by affecting endothelial cells, altering immunity, and disrupting the clotting system. Despite advances in treatments, such as cytokine blocking therapies, disease modifying treatment for this class of pathogen remains elusive. Improved understanding of the pathogenesis of these infections could provide new avenues to treatment. While animal models and traditional 2D cell cultures have contributed insight into the mechanisms by which these pathogens affect the vasculature, these models fall short in replicatingin vivohuman vascular dynamics. The emergence of microphysiological systems (MPSs) offers promising avenues for modeling these complex interactions. These MPS or 'organ-on-chip' models present opportunities to better mimic human vascular responses and thus aid in treatment development. In this review, we explore the impact of HFV on the vasculature by causing endothelial dysfunction, blood clotting irregularities, and immune dysregulation. We highlight how existing MPS have elucidated features of HFV pathogenesis as well as discuss existing knowledge gaps and the challenges in modeling these interactions using MPS. Understanding the intricate mechanisms of vascular dysfunction caused by HFV is crucial in developing therapies not only for these infections, but also for other vasculotropic conditions like sepsis.
Assuntos
Febres Hemorrágicas Virais , Humanos , Febres Hemorrágicas Virais/virologia , Animais , Células Endoteliais/patologia , Endotélio Vascular , Modelos BiológicosRESUMO
Assay validation is an essential component of disease surveillance testing, but can be problematic in settings where access to positive control material is limited and a safety risk for handlers. Here we describe a single non-infectious synthetic control that can help develop and validate the PCR based detection of the viral causes of Crimean-Congo hemorrhagic fever, Ebola virus disease, Lassa fever, Marburg virus disease and Rift Valley fever. We designed non-infectious synthetic DNA oligonucleotide sequences incorporating primer binding sites suitable for five assays, and a T7 promotor site which was used to transcribe the sequence. Transcribed RNA was used as template in a dilution series, extracted and amplified with RT-PCR and RT-qPCR to demonstrate successful recovery and determine limits of detection in a range of laboratory settings. Our results show this approach is adaptable to any diagnostic assay requiring validation of nucleic acid extraction and/or amplification, particularly where sourcing reliable, safe material for positive controls is infeasible.
Assuntos
Febres Hemorrágicas Virais , Humanos , Febres Hemorrágicas Virais/diagnóstico , Febres Hemorrágicas Virais/virologia , RNA Viral/genética , Reação em Cadeia da Polimerase em Tempo Real/métodos , Primers do DNA/genética , Sensibilidade e EspecificidadeRESUMO
Guanarito virus (GTOV) is the causative agent of Venezuelan hemorrhagic fever. GTOV belongs to the genus Mammarenavirus, family Arenaviridae and has been classified as a Category A bioterrorism agent by the United States Centers for Disease Control and Prevention. Despite being a high-priority agent, vaccines and drugs against Venezuelan hemorrhagic fever are not available. GTOV S-26764, isolated from a non-fatal human case, produces an unclear cytopathic effect (CPE) in Vero cells, posing a significant obstacle to research and countermeasure development efforts. Vero cell-adapted GTOV S-26764 generated in this study produced clear CPE and demonstrated rapid growth and high yield in Vero cells compared to the original GTOV S-26764. We developed a reverse genetics system for GTOV to study amino acid changes acquired through Vero cell adaptation and leading to virus phenotype changes. The results demonstrated that E1497K in the L protein was responsible for the production of clear plaques as well as enhanced viral RNA replication and transcription efficiency. Vero cell-adapted GTOV S-26764, capable of generating CPE, will allow researchers to easily perform neutralization assays and anti-drug screening against GTOV. Moreover, the developed reverse genetics system will accelerate vaccine and antiviral drug development.IMPORTANCEGuanarito virus (GTOV) is a rodent-borne virus. GTOV causes fever, prostration, headache, arthralgia, cough, sore throat, nausea, vomiting, diarrhea, epistaxis, bleeding gums, menorrhagia, and melena in humans. The lethality rate is 23.1% or higher. Vero cell-adapted GTOV S-26764 shows a clear cytopathic effect (CPE), whereas the parental virus shows unclear CPE in Vero cells. We generated a reverse genetics system to rescue recombinant GTOVs and found that E1497K in the L protein was responsible for the formation of clear plaques as well as enhanced viral RNA replication and transcription efficiency. This reverse genetic system will accelerate vaccine and antiviral drug developments, and the findings of this study contribute to the understanding of the function of GTOV L as an RNA polymerase.
Assuntos
Arenaviridae , Genética Reversa , Animais , Feminino , Humanos , Arenaviridae/genética , Infecções por Arenaviridae/virologia , Arenavirus do Novo Mundo/genética , Chlorocebus aethiops , Febres Hemorrágicas Virais/virologia , Fenótipo , Genética Reversa/métodos , Vacinas , Células VeroRESUMO
Simian arteriviruses are endemic in some African primates and can cause fatal hemorrhagic fevers when they cross into primate hosts of new species. We find that CD163 acts as an intracellular receptor for simian hemorrhagic fever virus (SHFV; a simian arterivirus), a rare mode of virus entry that is shared with other hemorrhagic fever-causing viruses (e.g., Ebola and Lassa viruses). Further, SHFV enters and replicates in human monocytes, indicating full functionality of all of the human cellular proteins required for viral replication. Thus, simian arteriviruses in nature may not require major adaptations to the human host. Given that at least three distinct simian arteriviruses have caused fatal infections in captive macaques after host-switching, and that humans are immunologically naive to this family of viruses, development of serology tests for human surveillance should be a priority.
Assuntos
Arterivirus , Febres Hemorrágicas Virais , Animais , Arterivirus/fisiologia , Febres Hemorrágicas Virais/veterinária , Febres Hemorrágicas Virais/virologia , Humanos , Macaca , Primatas , Zoonoses Virais , Internalização do Vírus , Replicação ViralRESUMO
BACKGROUND: In June 2019, the Bolivian Ministry of Health reported a cluster of cases of hemorrhagic fever that started in the municipality of Caranavi and expanded to La Paz. The cause of these cases was unknown. METHODS: We obtained samples for next-generation sequencing and virus isolation. Human and rodent specimens were tested by means of virus-specific real-time quantitative reverse-transcriptase-polymerase-chain-reaction assays, next-generation sequencing, and virus isolation. RESULTS: Nine cases of hemorrhagic fever were identified; four of the patients with this illness died. The etiologic agent was identified as Mammarenavirus Chapare mammarenavirus, or Chapare virus (CHAPV), which causes Chapare hemorrhagic fever (CHHF). Probable nosocomial transmission among health care workers was identified. Some patients with CHHF had neurologic manifestations, and those who survived had a prolonged recovery period. CHAPV RNA was detected in a variety of human body fluids (including blood; urine; nasopharyngeal, oropharyngeal, and bronchoalveolar-lavage fluid; conjunctiva; and semen) and in specimens obtained from captured small-eared pygmy rice rats (Oligoryzomys microtis). In survivors of CHHF, viral RNA was detected up to 170 days after symptom onset; CHAPV was isolated from a semen sample obtained 86 days after symptom onset. CONCLUSIONS: M. Chapare mammarenavirus was identified as the etiologic agent of CHHF. Both spillover from a zoonotic reservoir and possible person-to-person transmission were identified. This virus was detected in a rodent species, O. microtis. (Funded by the Bolivian Ministry of Health and others.).
Assuntos
Arenavirus do Novo Mundo , Febre Hemorrágica Americana , RNA Viral , Roedores , Animais , Arenavirus do Novo Mundo/genética , Arenavirus do Novo Mundo/isolamento & purificação , Bolívia/epidemiologia , Infecção Hospitalar/transmissão , Infecção Hospitalar/virologia , Transmissão de Doença Infecciosa , Febre Hemorrágica Americana/complicações , Febre Hemorrágica Americana/genética , Febre Hemorrágica Americana/transmissão , Febre Hemorrágica Americana/virologia , Febres Hemorrágicas Virais/genética , Febres Hemorrágicas Virais/transmissão , Febres Hemorrágicas Virais/virologia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Reação em Cadeia da Polimerase , RNA Viral/genética , RNA Viral/isolamento & purificação , Ratos/virologia , Roedores/virologia , Zoonoses Virais/transmissão , Zoonoses Virais/virologiaRESUMO
In the Americas, infectious viral diseases caused by viruses of the genus Mammarenavirus have been reported since the 1960s. Such diseases have commonly been associated with land use changes, which favor abundance of generalist rodent species. In the Americas-where the rates of land use change are among the highest worldwide-at least 1326 of all 2277 known rodent species have been reported. We conducted a literature review of studies between 1960 and 2020, to establish the current and historical knowledge about genotypes of mammarenaviruses and their rodent reservoirs in the Americas. Our overall goal was to show the importance of focusing research efforts on the American continent, since the conditions exist for future viral hemorrhagic fever (VHF) outbreaks caused by rodent-borne viruses, in turn, carried by widely distributed rodents. We found 47 species identified down to the species level, and one species identified only down to the genus level (Oryzomys sp.), reported in the Americas as reservoirs of mammarenaviruses, most these are ecological generalists. These species associate with 29 genotypes of Mammarenavirus, seven of which have been linked to VHFs in humans. We also highlight the need to monitor these species, in order to prevent viral disease outbreaks in the region.
Assuntos
Arenaviridae , Roedores , América , Animais , Arenaviridae/classificação , Arenaviridae/genética , Reservatórios de Doenças/virologia , Febres Hemorrágicas Virais/virologia , Roedores/virologiaRESUMO
Kyasanur Forest disease virus (KFDV) and the closely related Alkhurma hemorrhagic disease virus (AHFV) are emerging flaviviruses that cause severe viral hemorrhagic fevers in humans. Increasing geographical expansion and case numbers, particularly of KFDV in southwest India, class these viruses as a public health threat. Viral pathogenesis is not well understood and additional vaccines and antivirals are needed to effectively counter the impact of these viruses. However, current animal models of KFDV pathogenesis do not accurately reproduce viral tissue tropism or clinical outcomes observed in humans. Here, we show that pigtailed macaques (Macaca nemestrina) infected with KFDV or AHFV develop viremia that peaks 2 to 4 days following inoculation. Over the course of infection, animals developed lymphocytopenia, thrombocytopenia, and elevated liver enzymes. Infected animals exhibited hallmark signs of human disease characterized by a flushed appearance, piloerection, dehydration, loss of appetite, weakness, and hemorrhagic signs including epistaxis. Virus was commonly present in the gastrointestinal tract, consistent with human disease caused by KFDV and AHFV where gastrointestinal symptoms (hemorrhage, vomiting, diarrhea) are common. Importantly, RNAseq of whole blood revealed that KFDV downregulated gene expression of key clotting factors that was not observed during AHFV infection, consistent with increased severity of KFDV disease observed in this model. This work characterizes a nonhuman primate model for KFDV and AHFV that closely resembles human disease for further utilization in understanding host immunity and development of antiviral countermeasures.
Assuntos
Modelos Animais de Doenças , Vírus da Encefalite Transmitidos por Carrapatos/patogenicidade , Encefalite Transmitida por Carrapatos/virologia , Febres Hemorrágicas Virais/virologia , Macaca nemestrina , Animais , Chlorocebus aethiops , Citocinas/sangue , Vírus da Encefalite Transmitidos por Carrapatos/genética , Vírus da Encefalite Transmitidos por Carrapatos/imunologia , Encefalite Transmitida por Carrapatos/imunologia , Encefalite Transmitida por Carrapatos/patologia , Feminino , Células HEK293 , Febres Hemorrágicas Virais/imunologia , Febres Hemorrágicas Virais/patologia , Humanos , Linfonodos/virologia , Células Vero , ViremiaRESUMO
Rift Valley fever phlebovirus (RVFV) infects humans and a wide range of ungulates and historically has caused devastating epidemics in Africa and the Arabian Peninsula. Lesions of naturally infected cases of Rift Valley fever (RVF) have only been described in detail in sheep with a few reports concerning cattle and humans. The most frequently observed lesion in both ruminants and humans is randomly distributed necrosis, particularly in the liver. Lesions supportive of vascular endothelial injury are also present and include mild hydropericardium, hydrothorax and ascites; marked pulmonary congestion and oedema; lymph node congestion and oedema; and haemorrhages in many tissues. Although a complete understanding of RVF pathogenesis is still lacking, antigen-presenting cells in the skin are likely the early targets of the virus. Following suppression of type I IFN production and necrosis of dermal cells, RVFV spreads systemically, resulting in infection and necrosis of other cells in a variety of organs. Failure of both the innate and adaptive immune responses to control infection is exacerbated by apoptosis of lymphocytes. An excessive pro-inflammatory cytokine and chemokine response leads to microcirculatory dysfunction. Additionally, impairment of the coagulation system results in widespread haemorrhages. Fatal outcomes result from multiorgan failure, oedema in many organs (including the lungs and brain), hypotension, and circulatory shock. Here, we summarize current understanding of RVF cellular tropism as informed by lesions caused by natural infections. We specifically examine how extant knowledge informs current understanding regarding pathogenesis of the haemorrhagic fever form of RVF, identifying opportunities for future research.
Assuntos
Febres Hemorrágicas Virais/fisiopatologia , Febres Hemorrágicas Virais/veterinária , Febre do Vale de Rift/fisiopatologia , Vírus da Febre do Vale do Rift/patogenicidade , Tropismo Viral , Animais , Bovinos , Febres Hemorrágicas Virais/virologia , Humanos , Fígado/patologia , Fígado/virologia , Febre do Vale de Rift/virologia , Ovinos , Zoonoses Virais/fisiopatologiaRESUMO
BACKGROUND: Severe fever with thrombocytopenia syndrome virus (SFTSV) causes severe hemorrhagic fever in humans and cats. Clinical symptoms of SFTS-infected cats resemble those of SFTS patients, whereas SFTS-contracted cats have high levels of viral RNA loads in the serum and body fluids. Due to the risk of direct infection from SFTS-infected cats to human, it is important to diagnose SFTS-suspected animals. In this study, a reverse transcription polymerase chain reaction (RT-PCR) was newly developed to diagnose SFTS-suspected animals without non-specific reactions. METHODOLOGY/PRINCIPLE FINDINGS: Four primer sets were newly designed from consensus sequences constructed from 108 strains of SFTSV. A RT-PCR with these four primer sets successfully and specifically detected four clades of SFTSV. Their limits of detection are 1-10 copies/reaction. Using this RT-PCR, 5 cat cases among 56 SFTS-suspected animal cases were diagnosed as SFTS. From these cats, IgM or IgG against SFTSV were detected by enzyme-linked immunosorbent assay (ELISA), but not neutralizing antibodies by plaque reduction neutralization titer (PRNT) test. This phenomenon is similar to those of fatal SFTS patients. CONCLUSION/SIGNIFICANCE: This newly developed RT-PCR could detect SFTSV RNA of several clades and from SFTS-suspected animals. In addition to ELISA and PRNT test, the useful laboratory diagnosis systems of SFTS-suspected animals has been made in this study.
Assuntos
Phlebovirus/genética , Febre Grave com Síndrome de Trombocitopenia/diagnóstico , Febre Grave com Síndrome de Trombocitopenia/veterinária , Animais , Anticorpos Antivirais/imunologia , Infecções por Bunyaviridae/virologia , Gatos/virologia , Testes Diagnósticos de Rotina/métodos , Cães , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Febre/diagnóstico , Febres Hemorrágicas Virais/diagnóstico , Febres Hemorrágicas Virais/veterinária , Febres Hemorrágicas Virais/virologia , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Japão , Masculino , Phlebovirus/metabolismo , RNA Viral/sangue , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Febre Grave com Síndrome de Trombocitopenia/virologia , Trombocitopenia/diagnósticoRESUMO
Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging human pathogen, endemic in areas of China, Japan, and the Korea (KOR). It is primarily transmitted through infected ticks and can cause a severe hemorrhagic fever disease with case fatality rates as high as 30%. Despite its high virulence and increasing prevalence, molecular and functional studies in situ are scarce due to the limited availability of high-titer SFTSV exposure stocks. During the course of field virologic surveillance in 2017, we detected SFTSV in ticks and in a symptomatic soldier in a KOR Army training area. SFTSV was isolated from the ticks producing a high-titer viral exposure stock. Through the use of advanced genomic tools, we present here a complete, in-depth characterization of this viral stock, including a comparison with both the virus in its arthropod source and in the human case, and an in vivo study of its pathogenicity. Thanks to this detailed characterization, this SFTSV viral exposure stock constitutes a quality biological tool for the study of this viral agent and for the development of medical countermeasures, fulfilling the requirements of the main regulatory agencies.
Assuntos
Infecções por Bunyaviridae/virologia , Febres Hemorrágicas Virais/virologia , Phlebovirus/isolamento & purificação , Adulto , Animais , Infecções por Bunyaviridae/genética , Infecções por Bunyaviridae/metabolismo , Feminino , Genoma Viral , Humanos , Masculino , Camundongos , Phlebovirus/fisiologia , Filogenia , Receptor de Interferon alfa e beta/genética , Receptor de Interferon alfa e beta/metabolismo , República da Coreia , Carrapatos/virologiaRESUMO
With the COVID-19 officially declared a pandemic, Nigeria alongside other countries is directing all its resources and manpower to contain this pandemic. However, the existence of Lassa fever (LF), a more severe, zoonotic, endemic and viral haemorrhagic fever caused by Lassa virus with higher case fatality ratio (CFR) rages on across Nigeria while receiving little or no public health attention. The simultaneously increasing cases of COVID-19 and LF across Nigeria would be catastrophic unless infection prevention and control measures toward both LF and COVID-19 outbreaks are considered alongside.
Assuntos
Betacoronavirus/fisiologia , Infecções por Coronavirus/epidemiologia , Surtos de Doenças , Febres Hemorrágicas Virais/epidemiologia , Febre Lassa/epidemiologia , Vírus Lassa/fisiologia , Pandemias , Pneumonia Viral/epidemiologia , COVID-19 , Infecções por Coronavirus/virologia , Febres Hemorrágicas Virais/virologia , Humanos , Febre Lassa/virologia , Nigéria/epidemiologia , Pneumonia Viral/virologia , Saúde Pública , SARS-CoV-2RESUMO
INTRODUCTION: Arenavirus are unique category-A pathogens that are also classified as Orphan diseases. Very few options exist currently for treating Viral Hemorrhagic Fever (VHF) caused by viruses belonging to the Arenaviridae family [1]. The current review provides detailed patent landscape and a description of selected technologies developed for combating category-A Arenavirus. Currently, Arenavirus infections are epidemic [2] but could cause widespread pandemics due to ease of dissemination and lack of immunity against these viruses. AREAS COVERED: The key strings for selected Arenavirus VHF were run separately in MCPaIRS®, PatSeer, and Questel database. The search was limited to Title, Abstract and Claim fields; one member per patent family was considered for analysis. EXPERT OPINION: Synthetic molecules dominate the patent landscape, while natural products have not been extensively claimed for the treatment of Arenavirus infection. The broad-spectrum activity has been highly desired for Arenavirus treatment, but few reports have experimentally tested it. With each year, a constant increase in number of patents published is seen, while the maximum number of applications was filed in 2017. The research in VHF is driven by public funds; the maximum numbers of patents were filed by publicly funded organizations.
Assuntos
Antivirais/farmacologia , Infecções por Arenaviridae/tratamento farmacológico , Febres Hemorrágicas Virais/tratamento farmacológico , Animais , Infecções por Arenaviridae/virologia , Arenavirus/isolamento & purificação , Febres Hemorrágicas Virais/virologia , Humanos , Patentes como Assunto , Doenças Raras/tratamento farmacológico , Doenças Raras/virologiaRESUMO
African swine fever virus (ASFV) causes hemorrhagic fever in domestic pigs, presenting the biggest global threat to animal farming in recorded history. Despite the importance of ASFV, little is known about the mechanisms and regulation of ASFV transcription. Using RNA sequencing methods, we have determined total RNA abundance, transcription start sites, and transcription termination sites at single-nucleotide resolution. This allowed us to characterize DNA consensus motifs of early and late ASFV core promoters, as well as a polythymidylate sequence determinant for transcription termination. Our results demonstrate that ASFV utilizes alternative transcription start sites between early and late stages of infection and that ASFV RNA polymerase (RNAP) undergoes promoter-proximal transcript slippage at 5' ends of transcription units, adding quasitemplated AU- and AUAU-5' extensions to mRNAs. Here, we present the first much-needed genome-wide transcriptome study that provides unique insight into ASFV transcription and serves as a resource to aid future functional analyses of ASFV genes which are essential to combat this devastating disease.IMPORTANCE African swine fever virus (ASFV) causes incurable and often lethal hemorrhagic fever in domestic pigs. In 2020, ASF presents an acute and global animal health emergency that has the potential to devastate entire national economies as effective vaccines or antiviral drugs are not currently available (according to the Food and Agriculture Organization of the United Nations). With major outbreaks ongoing in Eastern Europe and Asia, urgent action is needed to advance our knowledge about the fundamental biology of ASFV, including the mechanisms and temporal control of gene expression. A thorough understanding of RNAP and transcription factor function, and of the sequence context of their promoter motifs, as well as accurate knowledge of which genes are expressed when and the amino acid sequence of the encoded proteins, is direly needed for the development of antiviral drugs and vaccines.
Assuntos
Vírus da Febre Suína Africana/genética , Febre Suína Africana/prevenção & controle , Transcrição Gênica/genética , Sequência de Aminoácidos , Animais , Genoma Viral , Febres Hemorrágicas Virais/virologia , Sus scrofa/virologia , Suínos/virologia , Terminação da Transcrição Genética , Ativação Transcricional/genética , Transcriptoma/genética , Proteínas Virais/genéticaRESUMO
Several clade B New World arenaviruses (NWAs) can cause severe and often fatal hemorrhagic fever, for which preventive and therapeutic measures are severely limited. These NWAs use human transferrin receptor 1 (hTfR1) as a host cell receptor for virus entry. The most prevalent of the pathogenic NWAs is Junín virus (JUNV), the etiological agent of Argentine hemorrhagic fever. Small animal models of JUNV infection are limited because most laboratory rodent species are refractory to disease. Only guinea pigs are known to develop disease following JUNV infection, but the underlying mechanisms are not well characterized. In the present study, we demonstrate marked susceptibility of Hartley guinea pigs to uniformly lethal disease when challenged with as few as 4 PFU of the Romero strain of JUNV. In vitro, we show that infection of primary guinea pig macrophages results in greater JUNV replication compared to infection of hamster or mouse macrophages. We provide evidence that the guinea pig TfR1 (gpTfR1) is the principal receptor for JUNV, while hamster and mouse orthologs fail to support viral entry/infection of pseudotyped murine leukemia viruses expressing pathogenic NWA glycoproteins or JUNV. Together, our results indicate that gpTfR1 serves as the primary receptor for pathogenic NWAs, enhancing viral infection in guinea pigs.IMPORTANCE JUNV is one of five known NWAs that cause viral hemorrhagic fever in humans. Countermeasures against JUNV infection are limited to immunization with the Candid#1 vaccine and immune plasma, which are available only in Argentina. The gold standard small animal model for JUNV infection is the guinea pig. Here, we demonstrate high sensitivity of this species to severe JUNV infection and identify gpTfR1 as the primary receptor. Use of hTfR1 for host cell entry is a feature shared by pathogenic NWAs. Our results show that expression of gpTfR1 or hTfR1 comparably enhances JUNV virus entry/infectivity. Our findings shed light on JUNV infection in guinea pigs as a model for human disease and suggest that similar pathophysiological mechanisms related to iron sequestration during infection and regulation of TfR1 expression may be shared between humans and guinea pigs. A better understanding of the underlying disease process will guide development of new therapeutic interventions.
Assuntos
Vírus Junin/imunologia , Vírus Junin/patogenicidade , Receptores da Transferrina/metabolismo , Animais , Arenavirus/imunologia , Arenavirus/patogenicidade , Células CHO , Chlorocebus aethiops , Cricetulus , Modelos Animais de Doenças , Feminino , Glicoproteínas/metabolismo , Cobaias/imunologia , Cobaias/metabolismo , Células HEK293 , Febre Hemorrágica Americana/imunologia , Febre Hemorrágica Americana/virologia , Febres Hemorrágicas Virais/imunologia , Febres Hemorrágicas Virais/virologia , Humanos , Vírus Junin/metabolismo , Macrófagos/virologia , Masculino , Receptores da Transferrina/imunologia , Células Vero , Internalização do Vírus , Replicação ViralRESUMO
Viral hemorrhagic fevers represent a group of diseases caused by enveloped RNA viruses. The epidemiology is broadly variable, ranging from geographically localized to more diffuse infections. Viral hemorrhagic fevers are classified as category A bioweapon agents by the Centers for Disease Control and Prevention. Viral hemorrhagic fevers are severe febrile illnesses with hemorrhagic phenomena. Laboratory diagnosis takes place in highly specialized reference laboratories. Treatment is essentially supportive. In this article, we focus the attention on yellow fever and viral hemorrhagic fevers other than Ebola and Lassa virus diseases that have been described elsewhere in this issue.
Assuntos
Febres Hemorrágicas Virais/epidemiologia , Febres Hemorrágicas Virais/virologia , Vírus de RNA/classificação , Saúde Global , HumanosRESUMO
Viral hemorrhagic fevers (VHFs) cause thousands of fatalities every year, but the treatment options for their management remain very limited. In particular, the development of therapeutic interventions is restricted by the lack of commercial viability of drugs targeting individual VHF agents. This makes approaches like drug repurposing and/or the identification of broad range therapies (i.e. those directed at host responses or common proviral factors) highly attractive. However, the identification of candidates for such antiviral repurposing or of host factors/pathways important for the virus life cycle is reliant on high-throughput screening (HTS). Recently, such screening work has been increasingly facilitated by the availability of reverse genetics-based approaches, including tools such as full-length clone (FLC) systems to generate reporter-expressing viruses or various life cycle modelling (LCM) systems, many of which have been developed and/or greatly improved during the last years. In particular, since LCM systems are capable of modelling specific steps in the life cycle, they are a valuable tool for both targeted screening (i.e. for inhibitors of a specific pathway) and mechanism of action studies. This review seeks to summarize the currently available reverse genetics systems for negative-sense VHF causing viruses (i.e. arenaviruses, bunyaviruses and filoviruses), and to highlight the recent advancements made in applying these systems for HTS to identify either antivirals or new virus-host interactions that might hold promise for the development of future treatments for the infections caused by these deadly but neglected virus groups.
Assuntos
Arenaviridae/genética , Bunyaviridae/genética , Filoviridae/genética , Febres Hemorrágicas Virais/virologia , Ensaios de Triagem em Larga Escala , Genética Reversa/métodos , Antivirais/isolamento & purificação , Arenaviridae/efeitos dos fármacos , Bunyaviridae/efeitos dos fármacos , Filoviridae/efeitos dos fármacos , Genoma Viral , Interações entre Hospedeiro e Microrganismos , HumanosRESUMO
BACKGROUND: Hantaviruses are a group of emerging pathogens causing hemorrhagic fever with renal syndrome and Hantavirus cardiopulmonary syndrome in human. This study was conducted to investigate Hantavirus infection among Iranian viral hemorrhagic fever suspected patients. METHODS: From April 2014 to June 2016, 113 cases from 25 different provinces of Iran were analyzed for Hantavirus infection by IgM/IgG ELISA and pan-Hantavirus RT-PCR tests. RESULTS: Although, viral genome was detected in none of the subjects, IgM and IgG antibodies were detected in 19 and 4 cases, respectively. Differentiation of the anti-Hantavirus antibodies according to virus species by EUROLINE Anti-Hantavirus Profile Kit revealed three Puumala virus IgM positive, one Hantaan virus IgM positive, one Hantaan virus IgM borderline, and two Puumala virus IgG borderline cases. CONCLUSIONS: This study demonstrates the circulation of Hantaviruses in Iran and calls for further investigations of these life-threatening viruses in the country.