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Viruses Nov 2012Lymphocytic choriomeningitis virus (LCMV) has contributed to unveil some of the molecular mechanisms of lethal mutagenesis, or loss of virus infectivity due to increased... (Review)
Review
Lymphocytic choriomeningitis virus (LCMV) has contributed to unveil some of the molecular mechanisms of lethal mutagenesis, or loss of virus infectivity due to increased mutation rates. Here we review these developments, and provide additional evidence that ribavirin displays a dual mutagenic and inhibitory activity on LCMV that can be relevant to treatment designs. Using 5-fluorouracil as mutagenic agent and ribavirin either as inhibitor or mutagen, we document an advantage of a sequential inhibitor-mutagen administration over the corresponding combination treatment to achieve a low LCMV load in cell culture. This advantage is accentuated in the concentration range in which ribavirin acts mainly as an inhibitor, rather than as mutagen. This observation reinforces previous theoretical and experimental studies in supporting a sequential inhibitor-mutagen administration as a possible antiviral design. Given recent progress in the development of new inhibitors of arenavirus replication, our results suggest new options of ribavirin-based anti-arenavirus treatments.
Topics: Animals; Antiviral Agents; Arenaviridae Infections; Arenavirus; Drug Therapy, Combination; Genes, Lethal; Genes, Viral; Humans; Lymphocytic choriomeningitis virus; Mutagenesis; Mutation; Ribavirin
PubMed: 23202505
DOI: 10.3390/v4112786 -
Virology Jun 2001Pirital-like virus isolates from rodents collected in a variety of habitats within a six-state area of central Venezuela were analyzed genetically by amplifying a...
Pirital-like virus isolates from rodents collected in a variety of habitats within a six-state area of central Venezuela were analyzed genetically by amplifying a portion of the nucleocapsid protein gene using RT-PCR. Comparisons of the sequences from 30 selected Pirital-like virus isolates demonstrated up to 26% divergence in nucleotide sequences and up to 16% divergence in deduced amino acid sequences. Within the Pirital monophyletic group, 14 distinct lineages or genotypes, differing by at least 6% in nucleotide sequences, were identified. Although sample sizes were small for some lineages, many of the different genotypes were sampled in only one region or locality, suggesting allopatric divergence. Complement fixation tests with representatives of the most divergent Pirital virus lineages failed to delineate multiple species or subtypes within the Pirital clade. These results indicate that the previously proposed 12% nucleocapsid protein amino acid sequence divergence cutoff value for delineating arenavirus species is not appropriate for the entire family. When individual clones were examined from PCR amplicons, a mean of 0.17% sequence diversity vs the consensus sequences was detected, suggesting diverse quasispecies populations within infected rodent hosts. Possible explanations for the extreme genetic diversity within and among Pirital virus populations in infected rodents are discussed.
Topics: Animals; Arenaviridae; Complement Fixation Tests; Genetic Variation; Molecular Sequence Data; Phylogeny; Rodentia; Serotyping; Venezuela
PubMed: 11414811
DOI: 10.1006/viro.2001.0954 -
Soins. Pathologie Tropicale 1986
Topics: Antibodies, Viral; Arenaviridae; Diagnosis, Differential; Humans; Lassa Fever
PubMed: 3635282
DOI: No ID Found -
Current Opinion in Virology Oct 2020Several mammarenaviruses can cause severe hemorrhagic fever disease with a very high case fatality rate, representing important threats to human health within the... (Review)
Review
Several mammarenaviruses can cause severe hemorrhagic fever disease with a very high case fatality rate, representing important threats to human health within the viruses' endemic regions. To date, there are no United States (US) Food and Drug Administration (FDA)-licensed vaccines available to combat mammarenavirus infections in humans, and current anti-mammarenavirus therapy is limited to off-label use of the guanosine analog ribavirin, which has limited efficacy and has been associated with significant side effects. Vaccination is one of the most effective ways to prevent viral diseases, and live-attenuated vaccines (LAVs) have been shown to often provide long-term protection against a subsequent natural infection by the corresponding virulent form of the virus. The development of mammarenavirus reverse genetics systems has provided investigators with a powerful approach for the investigation of the molecular and cell biology of mammarenaviruses and also for the generation of recombinant viruses containing predetermined mutations in their genome for their implementation as LAVs for the treatment of mammarenavirus infections. In this review, we summarize the current knowledge on the mammarenavirus molecular and cell biology, and the use of reverse genetic approaches for the generation of recombinant mammarenaviruses. Moreover, we briefly discus some novel LAV approaches for the treatment of mammarenavirus infections based on the use of reverse genetics approaches.
Topics: Animals; Arenaviridae; Arenaviridae Infections; Genome, Viral; Humans; Mice; Reverse Genetics; Vaccines, Attenuated; Viral Vaccines; Virus Replication
PubMed: 32721864
DOI: 10.1016/j.coviro.2020.06.011 -
Emerging Infectious Diseases Dec 2021We conducted a survey for group-specific indirect immunofluorescence antibody to mammarenaviruses by using Lassa fever and Mopeia virus antigens on serum specimens of...
We conducted a survey for group-specific indirect immunofluorescence antibody to mammarenaviruses by using Lassa fever and Mopeia virus antigens on serum specimens of 5,363 rodents of 33 species collected in South Africa and Zimbabwe during 1964-1994. Rodents were collected for unrelated purposes or for this study and stored at -70°C. We found antibody to be widely distributed in the 2 countries; antibody was detected in serum specimens of 1.2%-31.8% of 14 species of myomorph rodents, whereas 19 mammarenavirus isolates were obtained from serum specimens and viscera of 4 seropositive species. Phylogenetic analysis on the basis of partial nucleoprotein sequences indicates that 14 isolates from Mastomys natalensis, the Natal multimammate mouse, were Mopeia virus, whereas Merino Walk virus was characterized as a novel virus in a separate study. The remaining 4 isolates from 3 rodent species potentially constitute novel viruses pending full characterization.
Topics: Animals; Arenaviridae; Disease Reservoirs; Lassa virus; Murinae; Phylogeny; South Africa; Zimbabwe
PubMed: 34808083
DOI: 10.3201/eid2712.211088 -
Antiviral Research Dec 2008Several arenaviruses cause hemorrhagic fever (HF) in humans, and evidence indicates that the worldwide-distributed prototypic arenavirus lymphocytic choriomeningitis... (Review)
Review
Several arenaviruses cause hemorrhagic fever (HF) in humans, and evidence indicates that the worldwide-distributed prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) is a neglected human pathogen of clinical significance. Moreover, arenaviruses pose a biodefense threat. No licensed anti-arenavirus vaccines are available, and current anti-arenavirus therapy is limited to the use of ribavirin, which is only partially effective and is associated with anemia and other side effects. Therefore, it is important to develop effective vaccines and better antiviral drugs to combat the dual threats of naturally occurring and intentionally introduced arenavirus infections. The development of arenavirus reverse genetic systems is allowing investigators to conduct a detailed molecular characterization of the viral cis-acting signals and trans-acting factors that control each of the steps of the arenavirus life cycle, including RNA synthesis, packaging and budding. Knowledge derived from these studies is uncovering potential novel targets for therapeutic intervention, as well as facilitating the establishment of assays to identify and characterize candidate antiviral drugs capable of interfering with specific steps of the virus life cycle. Likewise, the ability to generate predetermined specific mutations within the arenavirus genome and analyze their phenotypic expression would significantly contribute to the elucidation of arenavirus-host interactions, including the basis of their ability to cause severe HF. This, in turn, could lead to the development of novel, potent and safe arenavirus vaccines.
Topics: Animals; Antiviral Agents; Arenaviridae Infections; Arenavirus; Drug Evaluation, Preclinical; Humans; Promoter Regions, Genetic; Viral Vaccines; Virus Physiological Phenomena
PubMed: 18782590
DOI: 10.1016/j.antiviral.2008.08.002 -
The Journal of General Virology Sep 1991In this study, overlapping cDNA clones covering the entire S RNA molecule of Junin virus, an arenavirus that causes Argentine haemorrhagic fever, were generated. The... (Comparative Study)
Comparative Study
In this study, overlapping cDNA clones covering the entire S RNA molecule of Junin virus, an arenavirus that causes Argentine haemorrhagic fever, were generated. The complete sequence of this 3400 nucleotide RNA was determined using the dideoxynucleotide chain termination method. The nucleocapsid protein (N) and the glycoprotein precursor (GPC) genes were identified as two non-overlapping open reading frames of opposite polarity, encoding primary translation products of 564 and 481 amino acids, respectively. Intracellular processing of the latter yields the glycoproteins found in the viral envelope. Comparison of the Junin virus N protein with the homologous proteins of other arenaviruses indicated that amino acid sequences are conserved, the identity ranging from 46 to 76%. The N-terminal half of GPC exhibits an even higher degree of conservation (54 to 82%), whereas the C-terminal half is less conserved (21 to 50%). In all comparisons the highest level of amino acid sequence identity was seen when Junin virus and Tacaribe virus sequences were aligned. The nucleotide sequence at the 5' end of Junin virus S RNA is not identical to that determined of the other sequenced arenaviruses. However, it is complementary to the 3'-terminal sequences and may form a very stable panhandle structure (delta G-242.7 kJ/mol) involving the complete non-coding regions upstream from both the N and GPC genes. In addition, a distinct secondary structure was identified in the intergenic region, downstream from the coding sequences; Junin virus S RNA shows a potential secondary structure consisting of two hairpin loops (delta G -163.2 and -239.3 kJ/mol) instead of the single hairpin loop that is usually found in other arenaviruses. The analysis of the arenavirus S RNA nucleotide sequences and their encoded products is discussed in relation to structure and function.
Topics: Amino Acid Sequence; Animals; Arenaviridae; Arenaviruses, New World; Base Sequence; Blotting, Northern; Capsid; Cell Line; Cloning, Molecular; Codon; Glycoproteins; Molecular Sequence Data; Nucleic Acid Conformation; Open Reading Frames; Protein Precursors; RNA, Viral; Vero Cells; Viral Core Proteins
PubMed: 1654373
DOI: 10.1099/0022-1317-72-9-2129 -
Archives of Virology 1989During approximately 35 years, investigators in various laboratories studying arbovirus ecology and epidemiology accumulated many virus isolates, more than 60 of which...
Electron microscopy and antigenic studies of uncharacterized viruses. I. Evidence suggesting the placement of viruses in families Arenaviridae, Paramyxoviridae, or Poxviridae.
During approximately 35 years, investigators in various laboratories studying arbovirus ecology and epidemiology accumulated many virus isolates, more than 60 of which were not characterized or placed in taxa. By a combination of electron microscopic and antigenic studies we collected information sufficient to provisionally classify 60 isolates. Electron microscopic observations suggest that 20 are members of the virus family Bunyaviridae, 20 Rhabdoviridae, 14 Reoviridae, one Togaviridae, one Paramyxoviridae (Mapuera virus, from a bat), and one Poxviridae (Yoka virus, from mosquitoes). Serologic studies provided evidence sufficient to place some of these viruses in recognized antigenic groups, within families and genera, and to establish new antigenic groups and taxa for others. Three viruses were found to have morphologic and morphogenetic characteristics consistent with those of members of the family Arenaviridae: Quaranfil virus, a human pathogen, Johnston Atoll virus, isolated from birds and ticks, and Araguari virus, isolated from an opossum. This, the first in a series of three papers, described methods used for these investigations and also presents descriptions of viruses provisionally placed in the families Arenaviridae, Paramyxoviridae, or Poxviridae. Descriptions of viruses provisionally placed in families Bunyaviridae and Reoviridae are published in the second and third papers, respectively. Viruses of the family Rhabdoviridae have been described separately.
Topics: Animals; Arenaviridae; Complement Fixation Tests; Cytopathogenic Effect, Viral; Fluorescent Antibody Technique; Hemagglutination Inhibition Tests; Mice; Paramyxoviridae; Poxviridae; Serotyping; Virus Cultivation
PubMed: 2690775
DOI: 10.1007/BF01310934 -
Advances in Virus Research 1986This chapter reviews the evidence that shows that arenaviruses and members of one genus of the Bunyaviridae (phleboviruses) have some proteins coded in subgenomic,... (Review)
Review
This chapter reviews the evidence that shows that arenaviruses and members of one genus of the Bunyaviridae (phleboviruses) have some proteins coded in subgenomic, viral-sense mRNA species and other proteins coded in subgenomic, viral-complementary mRNA sequences. This unique feature is discussed in relation to the implications it has on the intracellular infection process and how such a coding arrangement may have evolved. The chapter presents a list of the known members of the arenaviridae, their origins, and the vertebrate hosts from which isolates have been reported. It discusses the structural components, the infection cycle, and genetic attributes of arenaviruses. In order to determine how arenaviruses code for gene products, the S RNA species of Pichinde virus and that of a viscerotropic strain of LCM virus (LCM-WE) have been cloned into DNA and sequenced. The arenavirus S RNA is described as having an ambisense strategy, to denote the fact that both viral and viral-complementary sequences are used to make gene products. The chapter discusses the infection cycle, the structural and genetic properties of bunyaviridae member.
Topics: Animals; Arenaviridae; Arenaviridae Infections; Bunyaviridae; Bunyaviridae Infections; Cloning, Molecular; Genes, Viral; Genetic Code; Humans; Protein Biosynthesis; RNA, Messenger; RNA, Viral; Transcription, Genetic; Viral Proteins
PubMed: 3019106
DOI: 10.1016/s0065-3527(08)60261-4 -
Methods in Molecular Biology (Clifton,... 2018Identification of cell moieties involved in viral binding and internalization is essential since their expression would render a cell susceptible. Further steps that...
Identification of cell moieties involved in viral binding and internalization is essential since their expression would render a cell susceptible. Further steps that allow the uncoating of the viral particle at the right subcellular localization have been intensively studied. These "entry" steps could determine cell permissiveness and often define tissue and host tropism. Therefore applying the right and, when possible, straightforward experimental approaches would shorten avenues to the complete knowledge of this first and key step of any viral life cycle. Mammarenaviruses are enveloped viruses that enter the host cell via receptor-mediated endocytosis. In this chapter we present a set of customized experimental approaches and tools that were used to describe the entry of Junín virus (JUNV), and other New World mammarenavirus members, into mammalian cells.
Topics: Animals; Arenaviridae; Arenaviruses, New World; Endocytosis; Humans
PubMed: 28986829
DOI: 10.1007/978-1-4939-6981-4_8