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Annual Review of Virology Sep 2017Hemorrhagic fevers caused by viruses were identified in the late 1950s in South America. These viruses have existed in their hosts, the New World rodents, for millions... (Review)
Review
Hemorrhagic fevers caused by viruses were identified in the late 1950s in South America. These viruses have existed in their hosts, the New World rodents, for millions of years. Their emergence as infectious agents in humans coincided with changes in the environment and farming practices that caused explosions in their host rodent populations. Zoonosis into humans likely occurs because the pathogenic New World arenaviruses use human transferrin receptor 1 to enter cells. The mortality rate after infection with these viruses is high, but the mechanism by which disease is induced is still not clear. Possibilities include direct effects of cellular infection or the induction of high levels of cytokines by infected sentinel cells of the immune system, leading to endothelia and thrombocyte dysfunction and neurological disease. Here we provide a review of the ecology and molecular and cellular biology of New World arenaviruses, as well as a discussion of the current animal models of infection. The development of animal models, coupled with an improved understanding of the infection pathway and host response, should lead to the discovery of new drugs for treating infections.
Topics: Animals; Antigens, CD; Arenaviridae Infections; Arenaviruses, New World; Disease Models, Animal; Hemorrhagic Fevers, Viral; Host-Pathogen Interactions; Humans; Mice; Receptors, Transferrin; Receptors, Virus; Rodentia; Zoonoses
PubMed: 28645238
DOI: 10.1146/annurev-virology-101416-042001 -
Uirusu 2012Arenaviruses are the collective name for viruses, which belong to the family Arenaviridae. They replicate in the cytoplasm of cells, and were named after the sandy... (Review)
Review
Arenaviruses are the collective name for viruses, which belong to the family Arenaviridae. They replicate in the cytoplasm of cells, and were named after the sandy (Latin, arenosus) appearance of the ribosomes often seen in thin sections of virions under electron microscope. Several arenaviruses, such as Lassa virus in West Africa, and Junin, Guanarito, Sabia, Machupo, and Chapare viruses in South America, cause sever viral hemorrhagic fevers (VHF) in humans and represent a serious public health problem. These viruses are categorized as category 1 pathogens thus should be handles in a BSL4 laboratory. Recently, Lujo virus was isolated as a newly discovered novel arenavirus associated with a VHF outbreak in southern Africa in 2008. Although, we have no VHF patients caused by arenaviruses in Japan, except for a single imported Lassa fever case in 1987, it is possible that VHF patients occur as imported cases as for other VHF in the future. Therefore, it is necessary to develop the diagnostics and therapeutics in consideration of patient's severe symptoms and high mortality even in the disease-free countries. In this review, we will broadly discuss the current knowledge from the basic researches to diagnostics and vaccine developments for arenavirus diseases.
Topics: Animals; Arenaviridae Infections; Arenavirus; Clinical Laboratory Techniques; Genetic Structures; Genome, Viral; Humans; Receptors, Virus; Reverse Genetics; Viral Proteins; Viral Vaccines; Virion
PubMed: 24153233
DOI: 10.2222/jsv.62.229 -
Emerging Microbes & Infections Dec 2023Emerging zoonoses of wildlife origin caused by previously unknown agents are one of the most important challenges for human health. The Qinghai-Tibet Plateau represents...
Emerging zoonoses of wildlife origin caused by previously unknown agents are one of the most important challenges for human health. The Qinghai-Tibet Plateau represents a unique ecological niche with diverse wildlife that harbours several human pathogens and numerous previously uncharacterized pathogens. In this study, we identified and characterized a novel arenavirus (namely, plateau pika virus, PPV) from plateau pikas () on the Qinghai-Tibet Plateau by virome analysis. Isolated PPV strains could replicate in several mammalian cells. We further investigated PPV pathogenesis using animal models. PPV administered via an intraventricular route caused trembling and sudden death in IFNαβR mice, and pathological inflammatory lesions in brain tissue were observed. According to a retrospective serological survey in the geographical region where PPV was isolated, PPV-specific IgG antibodies were detected in 8 (2.4%) of 335 outpatients with available sera. Phylogenetic analyses revealed that this virus was clearly separated from previously reported New and Old World mammarenaviruses. Under the co-speciation framework, the estimated divergence time of PPV was 77-88 million years ago (MYA), earlier than that of OW and NW mammarenaviruses (26-34 MYA).
Topics: Animals; Humans; Mice; Arenaviridae; Phylogeny; Retrospective Studies; Tibet; Animals, Wild; Lagomorpha
PubMed: 36939609
DOI: 10.1080/22221751.2023.2192816 -
The Yale Journal of Biology and Medicine May 1975
Topics: Animals; Arboviruses; Arenaviruses, New World; Chiroptera; Cricetinae; Hemorrhagic Fever, American; Humans; Lassa virus; Lymphocytic Choriomeningitis; Lymphocytic choriomeningitis virus; Mice; RNA Viruses; Rats
PubMed: 168692
DOI: No ID Found -
The Journal of General Virology Sep 2023is a family for ambisense RNA viruses with genomes of about 10.5 kb that infect mammals, snakes, and fish. The arenavirid genome consists of two or three...
is a family for ambisense RNA viruses with genomes of about 10.5 kb that infect mammals, snakes, and fish. The arenavirid genome consists of two or three single-stranded RNA segments and encodes a nucleoprotein (NP), a glycoprotein (GP) and a large (L) protein containing RNA-directed RNA polymerase (RdRP) domains; some arenavirids encode a zinc-binding protein (Z). This is a summary of the International Committee on Taxonomy of Viruses (ICTV) report on the family , which is available at www.ictv.global/report/arenaviridae.
Topics: Animals; Arenaviridae; Nucleoproteins; RNA; RNA-Dependent RNA Polymerase; Mammals
PubMed: 37698490
DOI: 10.1099/jgv.0.001891 -
Methods in Molecular Biology (Clifton,... 2022Reverse genetics systems provide a powerful tool to generate recombinant arenavirus expressing reporters to facilitate the investigation of the arenavirus life cycle and...
Reverse genetics systems provide a powerful tool to generate recombinant arenavirus expressing reporters to facilitate the investigation of the arenavirus life cycle and also for the discovery of antiviral countermeasures. The plasmid-encoded viral ribonucleoprotein components initiate the transcription and replication of a plasmid-driven full-length viral genome, resulting in infectious virus. Thereby, this approach is ideal for the generation of recombinant arenaviruses expressing reporter genes that can be used as valid surrogates for virus replication. By splitting the small viral segment (S) into two viral segments (S1 and S2), each of them encoding a reporter gene, recombinant tri-segmented arenavirus can be rescued. Bi-reporter-expressing recombinant tri-segmented arenaviruses represent an excellent tool to study the biology of arenaviruses, including the identification and characterization of both prophylactic and therapeutic countermeasures for the treatment of arenaviral infections. In this chapter, we describe a detailed protocol on the generation and in vitro characterization of recombinant arenaviruses containing a tri-segment genome expressing two reporter genes based on the prototype member in the family, lymphocytic choriomeningitis virus (LCMV). Similar experimental approaches can be used for the generation of bi-reporter-expressing tri-segment recombinant viruses for other members in the arenavirus family.
Topics: Arenaviridae Infections; Genes, Reporter; Humans; Lymphocytic choriomeningitis virus; Reverse Genetics; Virus Replication
PubMed: 35821475
DOI: 10.1007/978-1-0716-2453-1_17 -
Uirusu 2018Arenavirus is a genetic term for viruses belonging to the family Arenaviridae and is presented from lymphocytic choriomeningitis virus (LCMV), which shows almost no... (Review)
Review
Arenavirus is a genetic term for viruses belonging to the family Arenaviridae and is presented from lymphocytic choriomeningitis virus (LCMV), which shows almost no pathogenicity to humans, to Lassa virus, Junin virus, Machupo virus, Chapare virus, Lujo virus, Sabia virus, and Guanarito virus, which shows high pathogenicity to humans. These viruses except for LCMV are risk group 4 pathogens specified by World Health Organization. Based on this designation, it is designated as Class I pathogens in Japan. Although there have been no reports excluding one imported case of the Lassa fever patient, it is not surprising whenever imported cases occur in our country. Considering the disease severity and mortality rate, it is an urgent matter to develop vaccines and therapeutic drugs in endemic areas, and maintenances of these are also important in countries other than endemic areas. However, basic research on highly pathogenic arenavirus infections and development of therapeutic drugs are not easily progressed, because handling in highly safe research facilities is indispensable. In this article, we will outline the current knowledge from the recent basic research on arenavirus to the development situation of antivirals against arenaviruses.
Topics: Africa, Western; Antiviral Agents; Arenaviridae Infections; Arenavirus; Disease Outbreaks; Drug Discovery; Genome, Viral; Humans; Research; Transcription, Genetic; Viral Vaccines; Virion
PubMed: 31105135
DOI: 10.2222/jsv.68.51 -
Current Topics in Microbiology and... 2016The family Arenaviridae currently comprises over 20 viral species, each of them associated with a main rodent species as the natural reservoir and in one case possibly... (Review)
Review
The family Arenaviridae currently comprises over 20 viral species, each of them associated with a main rodent species as the natural reservoir and in one case possibly phyllostomid bats. Moreover, recent findings have documented a divergent group of arenaviruses in captive alethinophidian snakes. Human infections occur through mucosal exposure to aerosols or by direct contact of abraded skin with infectious materials. Arenaviruses merit interest both as highly tractable experimental model systems to study acute and persistent infections and as clinically important human pathogens including Lassa (LASV) and Junin (JUNV) viruses, the causative agents of Lassa and Argentine hemorrhagic fevers (AHFs), respectively, for which there are no FDA-licensed vaccines, and current therapy is limited to an off-label use of ribavirin (Rib) that has significant limitations. Arenaviruses are enveloped viruses with a bi-segmented negative strand (NS) RNA genome. Each genome segment, L (ca 7.3 kb) and S (ca 3.5 kb), uses an ambisense coding strategy to direct the synthesis of two polypeptides in opposite orientation, separated by a noncoding intergenic region (IGR). The S genomic RNA encodes the virus nucleoprotein (NP) and the precursor (GPC) of the virus surface glycoprotein that mediates virus receptor recognition and cell entry via endocytosis. The L genome RNA encodes the viral RNA-dependent RNA polymerase (RdRp, or L polymerase) and the small (ca 11 kDa) RING finger protein Z that has functions of a bona fide matrix protein including directing virus budding. Arenaviruses were thought to be relatively stable genetically with intra- and interspecies amino acid sequence identities of 90-95 % and 44-63 %, respectively. However, recent evidence has documented extensive arenavirus genetic variability in the field. Moreover, dramatic phenotypic differences have been documented among closely related LCMV isolates. These data provide strong evidence of viral quasispecies involvement in arenavirus adaptability and pathogenesis. Here, we will review several aspects of the molecular biology of arenaviruses, phylogeny and evolution, and quasispecies dynamics of arenavirus populations for a better understanding of arenavirus pathogenesis, as well as for the development of novel antiviral strategies to combat arenavirus infections.
Topics: Animals; Antiviral Agents; Arenaviridae Infections; Arenavirus; Evolution, Molecular; Genetic Variation; Genome, Viral; Humans; Phylogeny; Virus Replication
PubMed: 26472215
DOI: 10.1007/82_2015_468 -
Clinical Microbiology and Infection :... Apr 2019Viral haemorrhagic fever can be caused by one of a diverse group of viruses that come from four different families of RNA viruses. Disease severity can vary from mild... (Review)
Review
Viral haemorrhagic fever can be caused by one of a diverse group of viruses that come from four different families of RNA viruses. Disease severity can vary from mild self-limiting febrile illness to severe disease characterized by high fever, high-level viraemia, increased vascular permeability that can progress to shock, multi-organ failure and death. Despite the urgent need, effective treatments and preventative vaccines are currently lacking for the majority of these viruses. A number of factors preclude the effective study of these diseases in humans including the high virulence of the agents involved, the sporadic nature of outbreaks of these viruses, which are typically in geographically isolated areas with underserviced diagnostic capabilities, and the requirements for high level bio-containment. As a result, animal models that accurately mimic human disease are essential for advancing our understanding of the pathogenesis of viral haemorrhagic fevers. Moreover, animal models for viral haemorrhagic fevers are necessary to test vaccines and therapeutic intervention strategies. Here, we present an overview of the animal models that have been established for each of the haemorrhagic fever viruses and identify which aspects of human disease are modelled. Furthermore, we discuss how experimental design considerations, such as choice of species and virus strain as well as route and dose of inoculation, have an influence on animal model development. We also bring attention to some of the pitfalls that need to be avoided when extrapolating results from animal models.
Topics: Animals; Arenaviridae; Bunyaviridae; Disease Models, Animal; Filoviridae; Flaviviridae; Hemorrhagic Fevers, Viral; Humans
PubMed: 24690109
DOI: 10.1111/1469-0691.12630 -
Viruses Oct 2012Arenaviruses include lethal human pathogens which pose serious public health threats. So far, no FDA approved vaccines are available against arenavirus infections, and... (Review)
Review
Arenaviruses include lethal human pathogens which pose serious public health threats. So far, no FDA approved vaccines are available against arenavirus infections, and therapeutic options are limited, making the identification of novel drug targets for the development of efficacious therapeutics an urgent need. Arenaviruses are comprised of two RNA genome segments and four proteins, the polymerase L, the envelope glycoprotein GP, the matrix protein Z, and the nucleoprotein NP. A crucial step in the arenavirus life-cycle is the biosynthesis and maturation of the GP precursor (GPC) by cellular signal peptidases and the cellular enzyme Subtilisin Kexin Isozyme-1 (SKI-1)/Site-1 Protease (S1P) yielding a tripartite mature GP complex formed by GP1/GP2 and a stable signal peptide (SSP). GPC cleavage by SKI-1/S1P is crucial for fusion competence and incorporation of mature GP into nascent budding virion particles. In a first part of our review, we cover basic aspects and newer developments in the biosynthesis of arenavirus GP and its molecular interaction with SKI-1/S1P. A second part will then highlight the potential of SKI-1/S1P-mediated processing of arenavirus GPC as a novel target for therapeutic intervention to combat human pathogenic arenaviruses.
Topics: Amino Acid Sequence; Antiviral Agents; Arenaviridae Infections; Arenavirus; Glycosylation; Golgi Apparatus; Humans; Proprotein Convertases; Protein Sorting Signals; Proteolysis; Pyrrolidines; Receptors, Cell Surface; Serine Endopeptidases; Viral Envelope Proteins; Virus Assembly; Virus Attachment
PubMed: 23202458
DOI: 10.3390/v4102162