Disease relevance of Arenavirus

• Here we report that lymphocytic choriomeningitis virus, the prototype arenavirus, is extremely susceptible to extinction mutagenesis by the base analog 5-fluorouracil [1].
• A crucial role of the LARGE-dependent glycosylation of alpha-DG for virus binding is found for several isolates of LCMV, LFV, and the arenaviruses Mobala and Oliveros [2].
• As reported herein, this requirement appears to be broadly applicable to the arenaviruses as determined by more extensive analysis of alpha-DG receptor usage and GP1 sequences of Old and New World arenaviruses [3].
• Tamiami virus, a member of the arenavirus group, produces an acute CNS disease in suckling mice manifested primarily by cerebellar ataxia, paralysis, convulsions, and death [4].
• These results strongly suggest that CCHF viruses (and other members of the genus Nairovirus) likely utilize the subtilase SKI-1/S1P-like cellular proteases for the major glycoprotein precursor cleavage events, as has recently been demonstrated for the arenaviruses [5].

High impact information on Arenavirus

• Recovery of an arenavirus entirely from RNA polymerase I/II-driven cDNA [6].
• Nucleocapsid protein gene of Junin arenavirus (cDNA sequence) [7].
• Initial work postulated that interactions between arenavirus glycoproteins and alpha-DG are based on protein-protein interactions [8].
• Posttranslational modification of alpha-dystroglycan, the cellular receptor for arenaviruses, by the glycosyltransferase LARGE is critical for virus binding [2].
• Studies based on the use of reverse-genetics approaches have provided direct experimental evidence of the key role played by the arenavirus L protein in viral-RNA synthesis [9].

Chemical compound and disease context of Arenavirus

• In contrast to the classical view that signal peptides act primarily in targeting nascent polypeptides to the endoplasmic reticulum, we suggest that the signal peptide of the arenavirus GP-C may serve additional functions in envelope glycoprotein structure and trafficking [10].
• All known arenavirus Z proteins contain a glycine (G) at position 2, which is a potential acceptor site for a myristoyl moiety [11].
• The yields of Pichinde virus, a member of the arenavirus group, were markedly inhibited when infected BHK 21 cells were incubated in the presence of 0.4 to 4 mug/ml of actinomycin D [12].
• Arenavirus inactivation on contact with N-substituted isatin beta-thiosemicarbazones and certain cations [13].
• Polyacrylamide gel electrophoretic analysis of RNA segments of the arenaviruses Pichinde (Pic) and Tacaribe (Tac) showed them to be distinguishable in that Pic S RNA had a slower electrophoretic mobility than Tac S RNA [14].

Biological context of Arenavirus

• Passage of the prototypic arenavirus lymphocytic choriomenigitis virus (LCMV) in cultured cells in the presence of the mutagenic agent 5-fluorouracil (FU) resulted in efficient and systematic virus extinction under conditions that did not significantly affect cell survival [15].
• They are included in the Category A Pathogen List established by the Center for Disease Control and Prevention that groups agents with the greatest potential for adverse public health impact and mass casualties whether a situation characterized by a ill-intentioned abuse of natural or engineered arenavirus would be encountered [16].

Anatomical context of Arenavirus

• Peptides with conservative aa exchanges, as they naturally occur in the epitope 289-301 of the Old World arenavirus Mopeia and some New World arenaviruses, continued to effectively stimulate the Lassa-GP2-specific T-cell clones tested [17].
• Splenic cytotoxic T-lymphocyte responses to LAS NP were detected after the boost and they cross-reacted with target cells infected with the related arenavirus, lymphocytic choriomeningitis virus [18].
• A novel nucleoside analog, 3'-fluoro-3'-deoxyadenosine (3'F3'dAdo), was evaluated for antiviral activity against several arthropod-borne and arenaviruses in Vero cell culture [19].
• Immunohistochemistry on formalin-fixed intestines, ceca, and bursae produced positive staining using an arenavirus antibody in epithelial cells of poults inoculated with the turkey homogenate and those inoculated with the Oakwood Agent [20].

Gene context of Arenavirus

• To date, the arenavirus Z protein associates with the promyelocytic leukemia protein PML and the ribosomal P proteins [21].
• Here, we observe that PML and arenavirus protein Z use regions around the first zinc-binding site of their respective RING domains to directly interact, with sub-micromolar affinity, with the dorsal surface of translation initiation factor eIF4E, representing a novel mode of eIF4E recognition [22].
• These findings reveal that the G2 envelope glycoprotein is more conserved among different arenaviruses than the internal nucleoprotein [23].
• The plaque reduction neutralization test (PRNT) has been used routinely in serological studies with such arenaviruses as Junin, Machupo, and Parana [24].
• Cells expressing the RING finger Z protein are resistant to arenavirus infection [25].

Analytical, diagnostic and therapeutic context of Arenavirus

• The high sensitivity of Junin virus to Ribavirin in vitro, the low toxicity of the drug for mammals and the therapeutic effect observed on in vivo infections with other arenaviruses, makes Ribavirin a promising antiviral agent that deserves testing on AHF primate models before clinical trials are undertaken [26].

References