Defective interfering Tacaribe virus and persistently infected cells

Gimenez, H. B.; Compans, Richard W.

doi:10.1016/0042-6822(80)90288-3

Cited by 26 publications

(9 citation statements)

References 24 publications

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“…Homotypic viral interference can be readily demonstrated with several arenaviruses, including LCMV (41) and TV (16). This phenomenon is not strictly strain specific, as illustrated by the existence of interference among different pairs of LCMV strains.…”

Section: Discussionmentioning

confidence: 89%

Characterization of the Arenavirus RING Finger Z Protein Regions Required for Z-Mediated Inhibition of Viral RNA Synthesis

Cornu

Torre

2002

J Virol

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The prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) is an enveloped virus with a bisegmented negative-strand RNA genome whose proteomic capability is limited to four polypeptides, namely, nucleoprotein; surface glycoprotein (GP), which is proteolytically processed into GP1 and GP2; polymerase (L); and a small (11-kDa) RING finger protein (Z). Using a reverse genetic system based on the ARM strain of LCMV, we have previously shown that Z has a strong inhibitory activity on LCMV minigenome transcription and RNA replication (T. I. Cornu and J. C. de la Torre, J. Virol. 75: [9415][9416][9417][9418][9419][9420][9421][9422][9423][9424][9425][9426] 2001). In the present study, we have identified regions and specific amino acid residues within Z which contribute to its inhibitory activity on RNA synthesis mediated by the LCMV polymerase. Z proteins from different LCMV strains had similar inhibitory activities on the expression of the LCMV ARM minigenome, whereas the Z protein of the genetically more distantly related Tacaribe virus had an approximately 10-fold lower inhibitory activity on ARM minigenome expression. Results from the use of chimera proteins between Z and Xenopus Neuralized, a nonviral RING finger protein, indicated that the structural integrity of the Z RING domain (RD) was required but not sufficient for the inhibitory activity of Z. Serial deletion mutants of the N and C termini of Z showed that the N terminus (residues 1 through 16) and C terminus (residues 79 through 90) do not contribute to the Z inhibitory activity. A highly conserved tryptophan (W) residue located at position 36 in ARM-Z, next to the second conserved cysteine (C) residue of the Z RD, also contributed to the Z inhibitory activity.Lymphocytic choriomeningitis virus (LCMV) provides one of the most widely used model systems to study viral persistence and pathogenesis (4, 5, 22-24, 26, 31). LCMV is the prototypic member of the family Arenaviridae that includes important human pathogens such as Lassa fever virus (LV) (6,27,28,37,39).The LCMV genome consists of two negative-sense, singlestranded RNA segments, designated L and S, with approximate sizes of 7.2 and 3.4 kb, respectively (30,33,36,37). Each RNA segment has an ambisense coding strategy, encoding two proteins in opposite orientations, separated by an intergenic region (33, 37). The S RNA segment directs synthesis of the three major structural proteins: the nucleoprotein, NP (ϳ63 kDa) (30,33,37), and the two virion glycoproteins, GP-1 (40 to 46 kDa) and GP-2 (35 kDa), which are derived from the posttranslational cleavage of a precursor polypeptide, GP-C (75 kDa) (33,37,38,42). Tetramers of GP-1 and GP-2 make up the spikes on the virion envelope and mediate virus interaction with the host cell surface receptor (3, 8). The L RNA segment encodes a high-molecular-mass protein, L (ϳ200 kDa) (36), and a small (11-kDa) RING finger protein (Z) (35). L has the characteristic motifs conserved in all the viral RNAdependent RNA polymerases (32) and is thought to be the main v...

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Section: Discussionmentioning

confidence: 89%

Characterization of the Arenavirus RING Finger Z Protein Regions Required for Z-Mediated Inhibition of Viral RNA Synthesis

Cornu

Torre

2002

J Virol

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“…There is experimental evidence that DI particles are involved in establishment and maintenance of long-term infection in tissue cultures (reviewed by Welsh & Oldstone [124]) and could completely prevent standard virus from producing cytopathology in certain cell lines (i.e., MDCK and PK-15 cells) [125,126]. Deletion of genetic material is known to be the principal characteristic of DI particles [125] and extensive deletions in S or L RNA segments were found for LCMV [127,128], TCRV [129], PICV [130], MACV, and LASV DI particles [33,131] as well. As seen in Fig.…”

Section: Overview Of Replication Strategymentioning

confidence: 99%

Lassa Virus Genome

Igor¹,

Sica²

2006

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Lassa virus (LASV), the most dangerous human pathogen among the Arenaviridae, belongs to a complex of genetically related virus strains responsible for the deaths of thousands of people in West Africa each year. The virus has a bi-segmented (L and S) single-stranded RNA genome. Each segment contains two genes in ambisense orientation. The L RNA encodes a large protein, L, or RdRp and a small zinc-binding, Z protein. The S RNA encodes the major structural proteins, nucleoprotein (NP) and glycoprotein precursor (GPC), cleaved into signal peptide, GP1, and GP2 glycoproteins. Genetic diversity among LASV strains is the highest within the family Arenaviridae and NP and RdRp genes are the most variable among LASV genes. The LASV genetic diversity is a great challenge for vaccine development.In addition to LASV and the prototype lymphocytic choriomeningitis virus (LCMV), the Old World group of arenaviruses includes three other related viruses, Mopeia (MOPV), Mobala (MOBV), and Ippy (IPPYV). These viruses as well as a MOP/LAS reassortant carrying the L RNA segment from MOPV and S RNA segment from LASV are non-pathogenic for experimental animals and are able to induce protective immunity against LASV. Lassa Fever pathogenesis is a sum of the effects induced by viral replication and immune response. The goal of this review is to cover recent publications on viral and host genes that control LASV virulence. The full-length genome sequence of LASV isolates and LASV-related nonpathogenic arenaviruses will provide a useful genetic tool to map LASV genes involved in virulence and to gain insight into phylogeny and evolution of the Old World arenaviruses.

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“…The nucleotide sequence within this intergenic region is such that a hairpin structure can be formed that would be stabilized by 14 G-C and 4 A-U base pairs (bp). GIMENEZ and COMPANS (1980) have shown that in cells persistently infected with Tacaribe virus the viral GPC is present only at very low levels, although the NP is abundant. 4.…”

Section: The Intergenic Region Of the Arenavirus S Rnamentioning

confidence: 99%