Effects of Defective Interfering Viruses on Virus Replication and Pathogenesis In Vitro and In Vivo

Roux, Laurent; Simon, Anne; Holland, John J.

doi:10.1016/s0065-3527(08)60279-1

Cited by 220 publications

(175 citation statements)

References 136 publications

(41 reference statements)

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“…Negative-strand RNA viruses produce DI genomes, which include point mutations and deletions, and particles that can modulate replication of the corresponding standard virus (Holland, 1990;Palma & Huang, 1974;Roux et al, 1991). LCMV gene expression can be regulated by different types of DI genomes (Meyer & Southern, 1997;Popescu et al, 1976;Welsh & Buchmeier, 1979;Welsh & Oldstone, 1977;.…”

Section: Discussionmentioning

confidence: 99%

An interfering activity against lymphocytic choriomeningitis virus replication associated with enhanced mutagenesis

Martı́n

Abia

Domingo

et al. 2009

Journal of General Virology

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Previous studies have documented that, in the presence of the mutagenic base analogue 5-fluorouracil (FU), lymphocytic choriomeningitis virus (LCMV) that persisted in BHK-21 cells decreased its infectivity to a larger extent than intracellular viral RNA levels, prior to virus extinction. This observation, together with in silico simulations, led to the proposal of the lethal defection model of virus extinction. This model suggests the participation of defective-interfering genomes in the loss of infectivity by increased mutagenesis. Since LCMV naturally produces defective-interfering particles, it was important to show that a capacity to interfere is produced in association with FU treatment. Here, we document that BHK-21 cells persistently infected with LCMV grown in the presence of FU, but not in its absence, generated an interfering activity that suppressed LCMV infectivity. Interference was specific for LCMV and was sensitive to UV irradiation and its activity was dose-and time-dependent. The interfering preparations produced positive LCMV immunofluorescence and viral particles seen by electron microscopy when used to infect cells, despite some preparations being devoid of detectable infectivity. Interference did not involve significant increases of mutant spectrum complexity, as predicted by the lethal defection model. The results provide support for a specific interference associated with LCMV when the virus replicates in the presence of FU. The excess of interference relative to that observed in the absence of FU is necessary for LCMV extinction.

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Section: Discussionmentioning

confidence: 99%

An interfering activity against lymphocytic choriomeningitis virus replication associated with enhanced mutagenesis

Martı́n

Abia

Domingo

et al. 2009

Journal of General Virology

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“…defective interfering RNA ͉ hypovirus ͉ RNA silencing ͉ RNA recombination V irus RNA recombination is an important component of virus evolution that contributes to the emergence of new viruses (reviewed in 1) and the generation of internally deleted mutant RNAs, termed defective interfering (DI) RNAs, that are derived from, and are dependent on, the parental viral genomic RNA (2). The presence of DI RNAs can suppress parental virus RNA accumulation, leading to attenuation of symptoms (3) and persistent virus infections (4,5).…”

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confidence: 99%

A host dicer is required for defective viral RNA production and recombinant virus vector RNA instability for a positive sense RNA virus

Zhang

Nuss

2008

Proc. Natl. Acad. Sci. U.S.A.

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Defective interfering (DI) RNAs, helper virus-dependent deletion mutant RNAs derived from the parental viral genomic RNA during replication, have been described for most RNA virus taxonomic groups. We now report that DI RNA production in the chestnut blight fungus, Cryphonectria parasitica, persistently infected by virulence-attenuating positive sense RNA hypoviruses, depends on one of two host dicer genes, dcl-2. We further report that nonviral sequences that are rapidly deleted from recombinant hypovirus RNA virus vectors in wild-type and dicer gene dcl-1 deletion mutant strains are stably maintained and expressed in the ⌬dcl-2 mutant strain. These results establish a requirement for dcl-2, the C. parasitica dicer gene responsible for antiviral defense and generation of virus-derived small interfering RNAs, in DI RNA production and recombinant virus vector RNA instability.defective interfering RNA ͉ hypovirus ͉ RNA silencing ͉ RNA recombination V irus RNA recombination is an important component of virus evolution that contributes to the emergence of new viruses (reviewed in 1) and the generation of internally deleted mutant RNAs, termed defective interfering (DI) RNAs, that are derived from, and are dependent on, the parental viral genomic RNA (2). The presence of DI RNAs can suppress parental virus RNA accumulation, leading to attenuation of symptoms (3) and persistent virus infections (4, 5). Rapid recombination also appears to be an underlying cause of the instability and deletion of foreign, nonviral sequences from recombinant viral RNA vectors (6; reviewed in 7). Genome instability presents one of the most important obstacles to the use of recombinant RNA viruses as gene expression vectors for various practical applications, including gene therapy (8-10).Single-strand, positive sense mycoviruses in the family Hypoviridae, hypoviruses that persistently infect and attenuate virulence of the chestnut blight fungus, Cryphonectria parastica, generate internally deleted DI RNAs at a very high frequency (11,12). Efforts to use recombinant hypoviruses to express foreign genes also have encountered the limitation of instable nonviral nucleotide sequences (13).We recently reported that disruption of one of two C. parasitica dicer genes, dcl-2, results in increased susceptibility to mycovirus infection (14). We subsequently showed that dcl-2 functions to process mycovirus RNAs into virus-derived small interfering RNAs (vsRNAs) as part of an inducible RNA silencing antiviral response (15). Cloning and characterization of vsRNAs generated from hypovirus CHV1-EP713 revealed a nonrandom distribution of vsRNAs along the 12.7-kb genome RNA. Conspicuous was the very low representation of vsRNA mapping to an internal portion of the 12.7-kb genome RNA that encodes the viral polymerase and helicase domains, from map position 7500 to 11000 (15). It has been postulated that the propensity of hypoviruses to generate internally deleted DI RNAs results in a lower level of substrate for vsRNA biogenesis from this region (15). Here ...

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confidence: 99%

“…DI RNAs interfere with helper virus replication probably through competition for replication and encapsidation proteins (Roux et aL, 1991). In model systems, it has been demonstrated that DI particles influence disease processes; however, whether they play a role in natural infections remains to be firmly established (Roux et al, 1991). Defective RNAs occur ubiquitously among animal RNA viruses and have also been described in association with the dsRNA killer virus of yeast (Kane et al, 1979;Bruenn, 1980) and many plant RNA viruses including the cherry strain of tomato bushy stunt tombusvirus (TBSV-Ch) (Hillman et al, 1987), cymbidium ringspot tombusvirus (CyRSV) (Burgyan et al, 1989), turnip crinkle carmovirus (TCV) (Li et al, 1989), clover yellow mosaic potexvirus (White et al, 1991) and tomato spotted wilt tospovirus (Resende et al, 1992).…”

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confidence: 99%

Sequence and structure of defective interfering RNAs associated with cucumber necrosis virus infections

Finnen

Rochon

1993

Journal of General Virology

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The presence of symptom-attenuating defective interfering (DI) RNAs in a laboratory culture of cucumber necrosis tombusvirus (CNV) was confirmed. Sequencing of eDNA clones of these DI RNAs revealed that CNV DI RNAs retained sequences from the CNV 5"-untranslated and T-terminal regions as well as a portion of the coding region for the 92K protein. Similar sequence arrangements were also observed in symptomattenuating DI RNAs generated de novo from synthetic wild-type CNV transcripts. A comparison of the sequences and biological activities of these CNV DI RNAs is presented. In co-infections of synthetic wildtype CNV and CNV DI RNAs, prominent RNA species of a higher M r than the DI RNA used in the co-infection were found. The possible nature of these RNA species is discussed.

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Effects of Defective Interfering Viruses on Virus Replication and Pathogenesis In Vitro and In Vivo

Cited by 220 publications

References 136 publications

An interfering activity against lymphocytic choriomeningitis virus replication associated with enhanced mutagenesis

An interfering activity against lymphocytic choriomeningitis virus replication associated with enhanced mutagenesis

A host dicer is required for defective viral RNA production and recombinant virus vector RNA instability for a positive sense RNA virus

Sequence and structure of defective interfering RNAs associated with cucumber necrosis virus infections

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