Subgenomic RNAs of Tacaribe Virus

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

doi:10.1007/978-1-4615-3028-2_7

Cited by 25 publications

(28 citation statements)

References 31 publications

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“…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

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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.

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Section: Introductionmentioning

confidence: 99%

Genome comparison of virulent and avirulent strains of the Pichinde arenavirus

et al. 2008

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“…220 kDa) and a small protein called Z (ca. 11 kDa) (4,15). Both L and N proteins are the minimal trans-acting factors required to drive full-cycle replication and transcription of the viral genome (20,26,30).…”

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confidence: 99%

Molecular Determinants of Arenavirus Z Protein Homo-Oligomerization and L Polymerase Binding

Loureiro

Wilda

Macleod

et al. 2011

J Virol

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The arenavirus Z is a zinc-binding RING protein that has been implicated in multiple functions during the viral life cycle. These roles of Z involve interactions with viral and cellular proteins that remain incompletely understood. In this regard, Z inhibits viral RNA transcription and replication through direct interaction with the viral L polymerase. Here, we defined the L-binding domain of Tacaribe virus (TCRV) Z protein and the structural requirements mediating Z homo-oligomerization. By using site-directed mutagenesis, coimmunoprecipitation, and functional assays, we showed that residues R37, N39, W44, L50, and Y57, located around the zinc coordination site I, play a critical role in the Z-L interaction. We also found that Z protein from either TCRV or the pathogenic Junin virus (JUNV) self-associates into oligomeric forms in mammalian cells. Importantly, mutation of the myristoylation site, the strictly conserved residue G at position 2, severely impaired the ability of both TCRV Z and JUNV Z to self-interact as well as their capacity to accumulate at the plasma membrane, strongly suggesting that Z homo-oligomerization is associated with its myristoylation and cell membrane targeting. In contrast, disruption of the RING structure or substitution of W44 or N39, which are critical for L protein recognition, did not affect Z self-binding. Overall, the data presented here indicate that homo-oligomerization is not a requirement for Z-L interaction or Z-mediated polymerase activity inhibition.

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“…The L RNA encodes the RNA-dependent RNA polymerase (RdRp) (L protein [240 kDa]) (16) and a small protein with a RING finger motif, called Z (11 kDa) (17). In both S and L RNAs, the genes are arranged in opposite orientations and are separated by noncoding sequences that have the potential to form stable secondary structures (14). S and L genomes and antigenomes are found only as nucleocapsids tightly bound to N protein, and the coding sequences are expressed from mRNAs transcribed from the 3Ј region of the genomes and antigenomes (1,14,20,27).…”

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confidence: 99%

“…In both S and L RNAs, the genes are arranged in opposite orientations and are separated by noncoding sequences that have the potential to form stable secondary structures (14). S and L genomes and antigenomes are found only as nucleocapsids tightly bound to N protein, and the coding sequences are expressed from mRNAs transcribed from the 3Ј region of the genomes and antigenomes (1,14,20,27). These mRNAs end within the intergenic region and contain short stretches of nontemplated nucleotides at their 5Ј ends, which are capped (20,21).…”

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confidence: 99%

Mapping of the Tacaribe Arenavirus Z-Protein Binding Sites on the L Protein Identified both Amino Acids within the Putative Polymerase Domain and a Region at the N Terminus of L That Are Critically Involved in Binding

Wilda

López

Casabona

et al. 2008

J Virol

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Tacaribe virus (TacV) is the prototype of the New World group of arenaviruses. The TacV genome encodes four proteins: the nucleoprotein (N), the glycoprotein precursor, the polymerase (L), and a RING finger protein (Z). Using a reverse genetics system, we demonstrated that TacV N and L are sufficient to drive transcription and replication mediated by TacV In the present study, we mapped the TacV Z-binding sites on the 2,210-amino-acid L polymerase. To that end, we performed deletion analysis and point mutations of L and studied the Z-L interaction by coimmunoprecipitation with specific sera. We found that the C-terminal region of L was not essential for the interaction and identified two noncontiguous regions that were critical for binding: one at the N-terminus of L between residues 156 and 292 and a second one in the polymerase domain (domain III). The importance of domain III in binding was revealed by substitutions in D1188 and H1189 within motif A and in each residue of the conserved SDD sequence (residues 1328, 1329, and 1330) within motif C. Our results showed that of the substituted residues, only H1189 and D1329 appeared to be critically involved in binding Z.Tacaribe virus (TacV) is the prototype of the New World group of arenaviruses. Within this group, the viruses form three phylogenetically distinct clades, one of which includes TacV together with the known South American pathogens that produce severe hemorrhagic disease: the Junin, Machupo, Guanarito, and Sabia viruses and the recently described Chapare virus (4, 7, 11). TacV, however, seems not to be a human pathogen.TacV is an enveloped virus containing two single-stranded RNA segments called S and L. The S RNA contains two genes encoding respectively the nucleoprotein (N [64 kDa]) and the glycoprotein precursor (55 kDa) of the surface glycoproteins (13). The L RNA encodes the RNA-dependent RNA polymerase (RdRp) (L protein [240 kDa]) (16) and a small protein with a RING finger motif, called Z (11 kDa) (17). In both S and L RNAs, the genes are arranged in opposite orientations and are separated by noncoding sequences that have the potential to form stable secondary structures (14). S and L genomes and antigenomes are found only as nucleocapsids tightly bound to N protein, and the coding sequences are expressed from mRNAs transcribed from the 3Ј region of the genomes and antigenomes (1,14,20,27). These mRNAs end within the intergenic region and contain short stretches of nontemplated nucleotides at their 5Ј ends, which are capped (20,21).Using a reconstituted transcription and replication system based on plasmid-supplied TacV RNAs and proteins, we demonstrated that L and N are the only viral proteins required for full-cycle RNA replication and transcription (22), for a faithful initiation of both processes, and for correct termination of mRNA transcription (21). Using this system, we also demonstrated that TacV Z protein is a potent inhibitor of both viral RNA replication and transcription (22). Lymphocytic choriomeningitis virus (LCMV) Z protein e...

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Subgenomic RNAs of Tacaribe Virus

Cited by 25 publications

References 31 publications

Genome comparison of virulent and avirulent strains of the Pichinde arenavirus

Genome comparison of virulent and avirulent strains of the Pichinde arenavirus

Molecular Determinants of Arenavirus Z Protein Homo-Oligomerization and L Polymerase Binding

Mapping of the Tacaribe Arenavirus Z-Protein Binding Sites on the L Protein Identified both Amino Acids within the Putative Polymerase Domain and a Region at the N Terminus of L That Are Critically Involved in Binding

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