The 3′ end termini of the tacaribe arenavirus subgenomic RNAs

Iapalucci, Silvia; López, Nora; Franze-Fernández, Marı́a T.

doi:10.1016/0042-6822(91)90670-7

Cited by 52 publications

(48 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Arrows represent L-mediated replication and transcription, and antigenomic-sense sequences are shown in gray. mRNAs contain a 5= m 7 G cap and terminate heterogeneously within the IGR (3= termini are arbitrarily depicted in the drawing) (23). Brackets on the full-length RNAs indicate the approximate location of the strand-specific RNA hybridization probes.…”

Section: Methodsmentioning

confidence: 99%

“…N-containing material was immunopurified using protein G Dynabeads (Life Technologies) and a mixture of four N-directed MAbs (BE06, (23). Arrows represent L-mediated replication and transcription, and antigenomic-sense sequences are shown in gray.…”

Section: Methodsmentioning

confidence: 99%

“…Viral mRNAs terminate within intergenic hairpin regions (IGRs) that separate the two opposite-sense open reading frames on the genomic RNAs ( Fig. 1) and are not polyadenylated (23). Based on a growing body of work describing the cytoplasmic life cycles of a number of RNA viruses (14,21,22,25,26,38), arenavirus replication is likely to be compartmentalized to specialized virus-induced organelles referred to as replication-transcription complexes (RTCs).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Arenavirus Infection Induces Discrete Cytosolic Structures for RNA Replication

Baird

York

Nunberg

2012

J Virol

View full text Add to dashboard Cite

Arenaviruses are responsible for acute hemorrhagic fevers with high mortality and pose significant threats to public health and biodefense. These enveloped negative-sense RNA viruses replicate in the cell cytoplasm and express four proteins. To better understand how these proteins insinuate themselves into cellular processes to orchestrate productive viral replication, we have identified and characterized novel cytosolic structures involved in arenavirus replication and transcription. In cells infected with the nonpathogenic Tacaribe virus or the attenuated Candid#1 strain of Junín virus, we find that newly synthesized viral RNAs localize to cytosolic puncta containing the nucleoprotein (N) of the virus. Density gradient centrifugation studies reveal that these replication-transcription complexes (RTCs) are associated with cellular membranes and contain full-length genomic-and antigenomic-sense RNAs. Viral mRNAs segregate at a higher buoyant density and are likewise scant in immunopurified RTCs, consistent with their translation on bulk cellular ribosomes. In addition, confocal microscopy analysis reveals that RTCs contain the lipid phosphatidylinositol-4-phosphate and proteins involved in cellular mRNA metabolism, including the large and small ribosomal subunit proteins L10a and S6, the stress granule protein G3BP1, and a subset of translation initiation factors. Elucidating the structure and function of RTCs will enhance our understanding of virus-cell interactions that promote arenavirus replication and mitigate against host cell immunity. This knowledge may lead to novel intervention strategies to limit viral virulence and pathogenesis.V iruses are wholly reliant on the host cell for replication. Viral proteins must access cellular systems to establish a productive environment for generating progeny virions while also evading the innate antiviral response. Viruses have therefore evolved diverse strategies and multifunctional proteins to coopt the host cell infrastructure. Elucidating these virus-cell interactions may suggest novel targets for antiviral intervention.Arenaviruses can cause acute hemorrhagic fevers with high mortality (34, 43). These viruses are endemic in rodent populations worldwide (47) and can be transmitted to humans by contact. Prototype arenavirus species include Lassa fever virus (LASV) in western Africa and Junín virus (JUNV) in the Pampas region of Argentina. These and other hemorrhagic fever arenaviruses pose ongoing threats to public health and raise concerns for biodefense planners. In the absence of licensed vaccines and specific antiviral therapies, these viruses are recognized as NIH category A priority pathogens (39). A critical understanding of the interactions of arenaviral proteins with the host cell will provide insight toward the development of effective therapies against arenavirus hemorrhagic fevers.The arenaviruses are a diverse family of enveloped negativesense RNA viruses that replicate entirely in the cell cytoplasm (9). The S and L RNA segments of the bipartite aren...

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Arenavirus Infection Induces Discrete Cytosolic Structures for RNA Replication

Baird

York

Nunberg

2012

J Virol

View full text Add to dashboard Cite

show abstract

“…A unique feature among the arenavirus genomic RNAs is the noncoding intergenic regions (IGRs) located between the two ORFs on each of the segments [7]. The IGRs, ranging from 59 to 217 nts in length, are predicted to form one to three energetically stable stem-loop structures in both the genomic and antigenomic RNAs [50] and are proposed to contribute to transcriptional termination [15,23,32,42]. Both L and NP proteins are essential for viral transcription and replication [41].…”

Section: Introductionmentioning

confidence: 99%

Genome comparison of virulent and avirulent strains of the Pichinde arenavirus

et al. 2008

View full text Add to dashboard Cite

A virulent (P18) strain of the Pichinde arenavirus produces a disease in guinea pigs that somewhat mimics human Lassa fever, whereas an avirulent (P2) strain of this virus is attenuated in infected animals. It has been speculated that the composition of viral genomes may confer the degree of virulence in an infected host; the complete sequence of the viral genomes, however, is not known. Here, we provide for the first time genomic sequences of both S and L segments for both the P2 and P18 strains. Sequence comparisons identify three mutations in the GP1 subunit of the viral glycoprotein, one in the nucleoprotein NP, and five in the viral RNA polymerase L protein. These mutations, alone or in combination, may contribute to the acquired virulence of Pichinde infection in animals. The 3 amino acid changes in the variable region of the GP1 glycoprotein subunit may affect viral entry by altering its receptor-binding activity. While NP has previously been shown to modulate the host immune responses to viral infection, we found that the R374K change in this protein does not affect the NP function in suppressing interferon-β expression. Four out of the five amino acid changes in the L protein occur in a small region of the protein that may contribute to viral virulence by enhancing its function on viral genomic RNA synthesis.

show abstract

“…The S segment (ϳ3.4 kb) encodes the glycoprotein precursor (GPC; ϳ75 kDa) and the nucleoprotein (N; ϳ65 kDa); while the L segment (ϳ7.2 kb) encodes the matrix protein (Z; ϳ11 kDa) and the viral polymerase (L; ϳ200 kDa). The coding regions of the segments are separated by an intergenic (IG) region with strong secondary structure, where transcription termination occurs (15,17,22,26). Interestingly, analyses of the lymphocytic choriomeningitis virus (LCMV) IG region revealed functions in both transcription termination and assembly or budding of virus particles (26).…”

mentioning

confidence: 99%

Efficient Rescue of Recombinant Lassa Virus Reveals the Influence of S Segment Noncoding Regions on Virus Replication and Virulence

Albariño

Bird

Chakrabarti

et al. 2011

J Virol

View full text Add to dashboard Cite

Lassa virus (LASV), is a significant cause of severe, often fatal, hemorrhagic fever in humans throughout western Africa, with an estimated 100,000 infections each year. No vaccines are commercially available. We report the development of an efficient reverse genetics system to rescue recombinant LASV and to investigate the contributions of the long 5 and 3 noncoding regions (NCRs) of the S genomic segment to in vitro growth and in vivo virulence. This work demonstrates that deletions of large portions of these NCRs confer an attenuated phenotype and are a first step toward further insights into the high virulence of LASV.

show abstract

The 3′ end termini of the tacaribe arenavirus subgenomic RNAs

Cited by 52 publications

References 20 publications

Arenavirus Infection Induces Discrete Cytosolic Structures for RNA Replication

Arenavirus Infection Induces Discrete Cytosolic Structures for RNA Replication

Genome comparison of virulent and avirulent strains of the Pichinde arenavirus

Efficient Rescue of Recombinant Lassa Virus Reveals the Influence of S Segment Noncoding Regions on Virus Replication and Virulence

Contact Info

Product

Resources

About