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Virus Research Apr 2017Bunyaviridae and Arenaviridae virus families include an important number of highly pathogenic viruses for humans. They are enveloped viruses with negative stranded RNA... (Review)
Review
Bunyaviridae and Arenaviridae virus families include an important number of highly pathogenic viruses for humans. They are enveloped viruses with negative stranded RNA genomes divided into three (bunyaviruses) or two (arenaviruses) segments. Each genome segment is coated by the viral nucleoproteins (NPs) and the polymerase (L protein) to form a functional ribonucleoprotein (RNP) complex. The viral RNP provides the necessary context on which the L protein carries out the biosynthetic processes of RNA replication and gene transcription. Decades of research have provided a good understanding of the molecular processes underlying RNA synthesis, both RNA replication and gene transcription, for these two families of viruses. In this review we will provide a global view of the common features, as well as differences, of the molecular biology of Bunyaviridae and Arenaviridae. We will also describe structures of protein and protein-RNA complexes so far determined for these viral families, mainly focusing on the L protein, and discuss their implications for understanding the mechanisms of viral RNA replication and gene transcription within the architecture of viral RNPs, also taking into account the cellular context in which these processes occur. Finally, we will discuss the implications of these structural findings for the development of antiviral drugs to treat human diseases caused by members of the Bunyaviridae and Arenaviridae families.
Topics: Arenaviridae; Bunyaviridae; Humans; Nucleoproteins; RNA-Dependent RNA Polymerase; Transcription, Genetic; Viral Proteins; Virus Replication
PubMed: 28137457
DOI: 10.1016/j.virusres.2017.01.018 -
Virulence Dec 2023
Topics: Humans; Arenaviridae; Viral Proteins; Arenaviridae Infections
PubMed: 37968871
DOI: 10.1080/21505594.2023.2279353 -
Viruses Jun 2021Mammarenaviruses are prevalent pathogens distributed worldwide, and several strains cause severe cases of human infections with high morbidity and significant mortality.... (Review)
Review
Mammarenaviruses are prevalent pathogens distributed worldwide, and several strains cause severe cases of human infections with high morbidity and significant mortality. Currently, there is no FDA-approved antiviral drugs and vaccines against mammarenavirus and the potential treatment option is limited to an off-label use of ribavirin that shows only partial protective effect and associates with side effects. For the past few decades, extensive research has reported potential anti-mammarenaviral drugs and their mechanisms of action in host as well as vaccine candidates. This review describes current knowledge about mammarenavirus virology, progress of antiviral drug development, and technical strategies of drug screening.
Topics: A549 Cells; Animals; Antiviral Agents; Arenaviridae; Chlorocebus aethiops; Clinical Trials as Topic; Drug Development; Drug Repositioning; HEK293 Cells; High-Throughput Screening Assays; Humans; Ribavirin; Vero Cells; Virus Replication
PubMed: 34206216
DOI: 10.3390/v13071187 -
Viruses Jul 2020is a family of viruses harbouring important emerging pathogens belonging to the order. Like in other segmented negative strand RNA viruses, the nucleoprotein (NP) is a... (Review)
Review
is a family of viruses harbouring important emerging pathogens belonging to the order. Like in other segmented negative strand RNA viruses, the nucleoprotein (NP) is a major actor of the viral life cycle being both (i) the necessary co-factor of the polymerase present in the L protein, and (ii) the last line of defence of the viral genome (vRNA) by physically hiding its presence in the cytoplasm. The NP is also one of the major players interfering with the immune system. Several structural studies of NP have shown that it features two domains: a globular RNA binding domain (NP-core) in its N-terminal and an exonuclease domain (ExoN) in its C-terminal. Further studies have observed that significant conformational changes are necessary for RNA encapsidation. In this review we revisited the most recent structural and functional data available on NP, compared to other nucleoproteins and explored the structural and functional implications. We review the variety of structural motif extensions involved in NP-NP binding mode. We also evaluate the major functional implications of NP interactome and the role of ExoN, thus making the NP a target of choice for future vaccine and antiviral therapy.
Topics: Arenaviridae; Nucleocapsid Proteins; Protein Structure, Tertiary; Virus Assembly
PubMed: 32708976
DOI: 10.3390/v12070772 -
Oncotarget Oct 2015
Topics: Arenaviridae Infections; Arenavirus; Exoribonucleases; Host-Pathogen Interactions; Humans; Interferon Type I; Viral Proteins
PubMed: 26468986
DOI: 10.18632/oncotarget.6110 -
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 -
Viruses May 2022Junín virus (JUNV) belongs to the family and is the causative agent of Argentine hemorrhagic fever (AHF), a severe human disease endemic to agricultural areas in... (Review)
Review
Junín virus (JUNV) belongs to the family and is the causative agent of Argentine hemorrhagic fever (AHF), a severe human disease endemic to agricultural areas in Argentina. At this moment, there are no effective antiviral therapeutics to battle pathogenic arenaviruses. Cumulative reports from recent years have widely provided information on cellular factors playing key roles during JUNV infection. In this review, we summarize research on host molecular determinants that intervene in the different stages of the viral life cycle: viral entry, replication, assembly and budding. Alongside, we describe JUNV tight interplay with the innate immune system. We also review the development of different reverse genetics systems and their use as tools to study JUNV biology and its close teamwork with the host. Elucidating relevant interactions of the virus with the host cell machinery is highly necessary to better understand the mechanistic basis beyond virus multiplication, disease pathogenesis and viral subversion of the immune response. Altogether, this knowledge becomes essential for identifying potential targets for the rational design of novel antiviral treatments to combat JUNV as well as other pathogenic arenaviruses.
Topics: Antiviral Agents; Arenaviridae; Arenavirus; Hemorrhagic Fever, American; Humans; Junin virus; Virus Replication
PubMed: 35746604
DOI: 10.3390/v14061134 -
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 -
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 -
Viruses Mar 2024The order includes at least fourteen families with diverse but related viruses, which are transmitted to vertebrate hosts by arthropod or rodent vectors. These viruses... (Review)
Review
The order includes at least fourteen families with diverse but related viruses, which are transmitted to vertebrate hosts by arthropod or rodent vectors. These viruses are responsible for an increasing number of outbreaks worldwide and represent a threat to public health. Infection in humans can be asymptomatic, or it may present with a range of conditions from a mild, febrile illness to severe hemorrhagic syndromes and/or neurological complications. There is a need to develop safe and effective vaccines, a process requiring better understanding of the adaptive immune responses involved during infection. This review highlights the most recent findings regarding T cell and antibody responses to the five families with known human pathogens (, , , , and ). Future studies that define and characterize mechanistic correlates of protection against infections or disease will help inform the development of effective vaccines.
Topics: Humans; RNA Viruses; Arenaviridae; Adaptive Immunity; Vaccines
PubMed: 38543848
DOI: 10.3390/v16030483