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Viruses Jul 2016Several arenaviruses cause hemorrhagic fever (HF) disease in humans and pose an important public health problem in their endemic regions. To date, no Food and Drug... (Review)
Review
Several arenaviruses cause hemorrhagic fever (HF) disease in humans and pose an important public health problem in their endemic regions. To date, no Food and Drug Administration (FDA)-licensed vaccines are available to combat human arenavirus infections, and current anti-arenaviral drug therapy is limited to an off-label use of ribavirin that is only partially effective. The development of arenavirus reverse genetic approaches has provided investigators with a novel and powerful approach for the study of arenavirus biology including virus-host interactions underlying arenavirus induced disease. The use of cell-based minigenome systems has allowed examining the cis- and trans-acting factors involved in arenavirus replication and transcription, as well as particle assembly and budding. Likewise, it is now feasible to rescue infectious arenaviruses containing predetermined mutations in their genomes to investigate virus-host interactions and mechanisms of pathogenesis. The use of reverse genetics approaches has also allowed the generation of recombinant arenaviruses expressing additional genes of interest. These advances in arenavirus molecular genetics have also facilitated the implementation of novel screens to identify anti-arenaviral drugs, and the development of novel strategies for the generation of arenavirus live-attenuated vaccines. In this review, we will summarize the current knowledge on reporter-expressing, replicating-competent arenaviruses harboring reporter genes in different locations of the viral genome and their use for studying and understanding arenavirus biology and the identification of anti-arenaviral drugs to combat these important human pathogens.
Topics: Animals; Arenavirus; Genes, Reporter; Humans; Reverse Genetics; Staining and Labeling; Virology; Virus Replication
PubMed: 27447662
DOI: 10.3390/v8070197 -
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 -
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 -
Oncotarget Oct 2015
Topics: Arenaviridae Infections; Arenavirus; Exoribonucleases; Host-Pathogen Interactions; Humans; Interferon Type I; Viral Proteins
PubMed: 26468986
DOI: 10.18632/oncotarget.6110 -
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 -
Viruses Apr 2021Rodent-borne arenaviruses have been traditionally predominantly associated with certain muroid species from genera (African arenaviruses) or with species that belong to...
Rodent-borne arenaviruses have been traditionally predominantly associated with certain muroid species from genera (African arenaviruses) or with species that belong to murid subfamily (New World arenaviruses) [...].
Topics: Amino Acid Sequence; Animals; Arenaviridae Infections; Arenavirus; Fishes; Humans; Rodentia; Snakes
PubMed: 33919632
DOI: 10.3390/v13040703 -
Current Topics in Microbiology and... 2007The Arenaviridae family contains 22 recognized virus species, each of them strongly associated with a rodent species (except Tacaribe virus which is associated with a... (Review)
Review
The Arenaviridae family contains 22 recognized virus species, each of them strongly associated with a rodent species (except Tacaribe virus which is associated with a species of bat), suggesting an ancient co-evolutionary process. Although the concept of co-evolution between rodents and arenaviruses is now largely accepted, little has been uncovered in terms of dating the phenomenon and the mechanisms of evolution, including speciation and pathogenicity. These questions are targeted in the present chapter. Old World arenaviruses are associated with the Eurasian rodents in the family Muridae. New World arenaviruses are associated with American rodents in the subfamily Sigmodontinae. The correlation between the rodent host phylogeny and the viruses suggests a long association and a co-evolutionary process. Furthermore, three distinct New World arenaviruses share a common ancestor, demonstrating a unique recombination event that probably occurred in that ancestor. This shows that recombination among arenaviruses of different lineages might occur in nature. Recombination and co-evolutionary adaptation appear as the main mechanisms of arenavirus evolution, generating a high degree of diversity. The diversity among rodent host reservoir and virus species and the potential to exchange genomic material provide a basis for the emergence of new viruses and the risk of these becoming pathogenic for humans.
Topics: Animals; Arenaviridae Infections; Arenavirus; Evolution, Molecular; Genetic Variation; Humans; Mutation; Recombination, Genetic; Rodent Diseases; Rodentia; Zoonoses
PubMed: 17848068
DOI: 10.1007/978-3-540-70962-6_11 -
Current Opinion in Virology Aug 2018The structure of a prefusion arenavirus GPC was enigmatic for many years, owing to the metastable and non-covalent nature of the association between the receptor binding... (Review)
Review
The structure of a prefusion arenavirus GPC was enigmatic for many years, owing to the metastable and non-covalent nature of the association between the receptor binding and fusion subunits. Recent engineering efforts to stabilize the glycoprotein of the Old World arenavirus Lassa in a native, yet cleaved state, allowed the first structure of any arenavirus prefusion GPC trimer to be determined. Comparison of this structure with the structures of other arenavirus glycoprotein subunits reveals surprising findings: that the receptor binding subunit, GP1, of Lassa virus is conformationally labile, while the GP1 subunit of New World arenaviruses is not, and that the arenavirus GPC adopts a trimeric state unlike other glycoproteins with similar fusion machinery. Structural analysis, combined with recent biochemical data regarding antibody epitopes and receptor binding requirements, provides a basis for rational vaccine design.
Topics: Arenavirus; Epitopes; Glycoproteins; Humans; Lassa virus; Protein Binding; Protein Structure, Tertiary; Viral Envelope Proteins; Virus Internalization
PubMed: 29843991
DOI: 10.1016/j.coviro.2018.05.002 -
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 -
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