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Current Opinion in Virology Feb 2019Next-generation sequencing technologies have revolutionized our knowledge of virus diversity and evolution. In the case of arenaviruses, which are the focus of this... (Review)
Review
Next-generation sequencing technologies have revolutionized our knowledge of virus diversity and evolution. In the case of arenaviruses, which are the focus of this review, metagenomic/metatranscriptomic approaches identified reptile-infecting and fish-infecting viruses, also showing that bi-segmented genomes are not a universal feature of the Arenaviridae family. Novel mammarenaviruses were described, allowing inference of their geographic origin and evolutionary dynamics. Extensive sequencing of Lassa virus (LASV) genomes revealed the zoonotic nature of most human infections and a Nigerian origin of LASV, which subsequently spread westward. Future efforts will likely identify many more arenaviruses and hopefully provide insight into the ultimate origin of the family, the pathogenic potential of its members, as well as the determinants of their geographic distribution.
Topics: Animals; Arenaviridae Infections; Arenavirus; Evolution, Molecular; Fishes; Genetic Variation; Genome, Viral; High-Throughput Nucleotide Sequencing; Host Microbial Interactions; Humans; Reptiles; Zoonoses
PubMed: 30497052
DOI: 10.1016/j.coviro.2018.11.001 -
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 -
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 -
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 -
Microbes and Infection Feb 2018In recent years there has been a greatly increased interest in the interactions of arenaviruses with the apoptotic machinery, and particularly the extent to which these... (Review)
Review
In recent years there has been a greatly increased interest in the interactions of arenaviruses with the apoptotic machinery, and particularly the extent to which these interactions may be an important contributor to pathogenesis. Here we summarize the current state of our knowledge on this subject and address the potential for interplay with other immunological mechanisms known to be regulated by these viruses. We also compare and contrast what is known for arenavirus-induced apoptosis with observations from other segmented hemorrhagic fever viruses.
Topics: Animals; Apoptosis; Arenaviridae Infections; Arenavirus; Humans; Immune Evasion; Immunity, Cellular; Nucleoproteins; Signal Transduction; Virus Replication
PubMed: 29081359
DOI: 10.1016/j.micinf.2017.10.002 -
Cellular Physiology and Biochemistry :... Nov 2021Viruses have been widely used to treat cancer for many years and they achieved tremendous success in clinical trials with outstanding results, which has led to the... (Review)
Review
Viruses have been widely used to treat cancer for many years and they achieved tremendous success in clinical trials with outstanding results, which has led to the foundation of companies that develop recombinant viruses for a better tumor treatment. Even though there has been a great progress in the field of viral tumor immunotherapy, until now only one virus, the oncolytic virus talimogene laherparepvec (TVEC), a genetically modified herpes simplex virus type 1 (T-VEC), has been approved by the FDA for cancer treatment. Although oncolytic viruses showed progress in certain cancer types and patient populations but they have yet shown limited efficacy when it comes to solid tumors. Only recently it was demonstrated that the immune stimulatory aspect of oncolytic viruses can strongly contribute to their anti-tumoral activity. One specific example in this context are arenaviruses, which have been shown to be non-cytopathic in nature lead to the massive immune activation within the tumor resulting in strong anti-tumoral activity. This strong immune activation might be also linked to their noncytopathic features, as their immune stimulatory potential is not self-limiting as is the case for oncolytic viruses due to their fast eradication by anti-viral immune effects. Because of this strong immune activation, arenaviruses appear superior to oncolytic viruses when it comes to potent and long-lasting anti-tumor effects in a broad variety of tumor types. Currently one of the most promising therapeutics which has turned to be very much beneficial for the treatment of different cancer types is represented by antibodies targeting checkpoint inhibitors such as PD-1/PD-L-1. In this review, we will summarize anti-tumoral effects of arenaviruses, and will discuss their potential to be combined with checkpoint inhibitors for a more efficient tumor treatment, which further emphasizes that arenavirus therapy as a viroimmunotherapy can be an efficient tool for the better clearance of tumors.
Topics: Arenavirus; Biological Products; Herpesvirus 1, Human; Humans; Immune Checkpoint Inhibitors; Neoplasms; Oncolytic Virotherapy; Oncolytic Viruses
PubMed: 34816678
DOI: 10.33594/000000472 -
Viruses Jan 2013Arenavirus particles are enveloped and contain two single-strand RNA genomic segments with ambisense coding. Genetic plasticity of the arenaviruses comes from... (Review)
Review
Arenavirus particles are enveloped and contain two single-strand RNA genomic segments with ambisense coding. Genetic plasticity of the arenaviruses comes from transcription errors, segment reassortment, and permissive genomic packaging, and results in their remarkable ability, as a group, to infect a wide variety of hosts. In this review, we discuss some in vitro studies of virus genetic and phenotypic variation after exposure to selective pressures such as high viral dose, mutagens and antivirals. Additionally, we discuss the variation in vivo of selected isolates of Old World arenaviruses, particularly after infection of different animal species. We also discuss the recent emergence of new arenaviruses in the context of our observations of sequence variations that appear to be host-specific.
Topics: Adaptation, Physiological; Animals; Arenaviridae Infections; Arenavirus; Biological Evolution; Host Specificity; Humans; Phylogeny
PubMed: 23344562
DOI: 10.3390/v5010241 -
FEBS Open Bio Apr 2021Arenaviruses are enveloped viruses containing a segmented, negative, and ambisense single-stranded RNA genome wrapped with a nucleoprotein (NP). The NP is the most...
Arenaviruses are enveloped viruses containing a segmented, negative, and ambisense single-stranded RNA genome wrapped with a nucleoprotein (NP). The NP is the most abundant viral protein in infected cells and plays a critical role in both replication/transcription and virion assembly. The NP associates with RNA to form a ribonucleoprotein (RNP) complex, and this implies self-assembly while the exact structure of this polymer is not yet known. Here, we report a measurement of the full-length Mopeia virus NP by negative stain transmission electron microscopy. We observed RNP complex particles with diameter 15 ± 1 nm as well as symmetric circular heptamers of the same diameter, consistent with previous observations.
Topics: Amino Acid Sequence; Arenavirus; Models, Molecular; Nucleoproteins; Protein Conformation; Protein Interaction Domains and Motifs; Protein Multimerization; RNA-Binding Proteins; Recombinant Proteins; Viral Proteins
PubMed: 33534950
DOI: 10.1002/2211-5463.13106 -
Viruses Jan 2013The Arenaviridae is a diverse and growing family of viruses that includes several agents responsible for important human diseases. Despite the importance of this family... (Review)
Review
The Arenaviridae is a diverse and growing family of viruses that includes several agents responsible for important human diseases. Despite the importance of this family for public health, particularly in Africa and South America, much of its biology remains poorly understood. However, in recent years significant progress has been made in this regard, particularly relating to the formation and release of new enveloped virions, which is an essential step in the viral lifecycle. While this process is mediated chiefly by the viral matrix protein Z, recent evidence suggests that for some viruses the nucleoprotein (NP) is also required to enhance the budding process. Here we highlight and compare the distinct budding mechanisms of different arenaviruses, concentrating on the role of the matrix protein Z, its known late domain sequences, and the involvement of cellular endosomal sorting complex required for transport (ESCRT) pathway components. Finally we address the recently described roles for the nucleoprotein NP in budding and ribonucleoprotein complex (RNP) incorporation, as well as discussing possible mechanisms related to its involvement.
Topics: Antiviral Agents; Arenaviridae Infections; Arenavirus; Endosomal Sorting Complexes Required for Transport; Host-Pathogen Interactions; Humans; Nucleoproteins; Protein Binding; Ribonucleoproteins; Signal Transduction; Viral Proteins; Virus Release
PubMed: 23435234
DOI: 10.3390/v5020528