Cyclic Production of Vesicular Stomatitis Virus Caused by Defective Interfering Particles

SUMMARYA persistent infection with rabies virus (HEP-Flury) was established in the CNS-derived hybrid cell line IO8 CC 15 which possesses specific membrane receptors for prostaglandins, catecholamines and acetylcholine. We report a differential virus influence on the specific receptor response to PGE, isoproterenol and acetycholine as indicated by typical changes of the intracellular cyclic AMP levels.As the adenylate cydase activity was unchanged in infected cells in vitro, a selective virus influence on specific receptors themselves or their coupling to the cAMP synthesizing system must be considered.

supporting

confidence: 73%

Rabies Virus Infection Selectively Impairs Membrane Receptor Functions in Neuronal Model Cells

Koschel

Halbach

1979

“…greater than presented here. This fluctuation is analogous at the intracellular level to that observed by Palma & Huang (1974) for VSV and by Kawai et al (1975) for rabies virus, where the relative concentrations of extracellular B and DI particles were observed to cycle in an out-of-phase manner due to the inhibition of virus by DI particles coupled with dependence upon helper virus. The total amount of actinomycin D-resistant incorporation of [3H]uridine into rabies nucleocapsid RNA (both B and DI) is also plotted in Fig.…”

Section: Characterization Of Intracellular Nucleoeapsids From Two Rabsupporting

confidence: 70%

Analysis of Viral and Defective-Interfering Nucleocapsids in Acute and Persistent Infection by Rhabdoviruses

Grabau

Holland

1982

SUMMARYWe have isolated and characterized the RNA of intracellular virus nucleocapsids recovered from a number of cell cultures persistently infected with rabies virus or vesicular stomatitis virus (VSV). VSV persistent infections in BHK21, L cells and Aedes albopictus (mosquito) cells generally showed the presence of large amounts of defective-interfering (DI) nucleocapsid RNA and much smaller amounts of standard (B) nucleocapsid RNA. Persistent infections of BHK21 cells by two rabies virus strains, challenge virus standard (CVS-11) or HEP-Flury, were followed for several months during which time the ratio of DI to B nucleocapsid RNA cycled dramatically. We also observed coordinated fluctuations in the absolute amount of incorporation of [3H]uridine into virus nucleocapsid RNA. Total incorporation was generally highest following a decrease in the relative amount of DI nucleocapsid RNA synthesis. At no time were DI nucleocapsids absent in any of the persistently infected cultures.

“…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

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.