Naslov
Selective irreversible inactivation of replicating mengovirus by nucleoside analogues : a new form of viral interference
(Selective irreversible inactivation of replicating mengovirus by nucleoside analogues : a new form of)

Autori
Brdar, Branko ; Reich, Edward

Izvornik
Journal of virology (0022-538X) 73 (1999), 8; 6444-6452

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
mengovirus; replication;viral interference; nucleoside analogues

Sažetak
We describe the selective irreversible inhibition of mengovirus growth in cultured cells by a combination of two pyrrolopyrimidine nucleoside analogues, 5-bromotubercidin (BrTu) and tubercidin (Tu). 5- Bromotubercidin at a concentration (5 mg/ml) which is sufficient to block the synthesis of cellular mRNA and rRNA reversibly, did not inhibit either RNA synthesis or growth of mengovirus. Being a potent adenosine kinase inhibitor, BrTu at a low concentration (0.5 mg/ml) which is insufficient to inhibit cell division, limited the cellular uptake of a more cytotoxic Tu, and protected the cells against irreversible damage resulting from Tu incorporation into nucleic acids. On the other hand, BrTu did not inhibit Tu incorporation into mengovirus RNA in virus infected cells, giving rize to functionally defective polynucleotides that are incapable of maintaining the virus growth cycle. This increased incorporation of Tu coupled to mengovirus infection could be attributed to a reduction in the inhibitory action of BrTu and/or its nucleotide derivatives at the level of nucleoside and nucleotide kinases. The virus life cycle in nucleoside treated cells progressed to the point of synthesis of the minus strands, and probably to the production of some new plus strands. Irreversible virus growth arrest was achieved if nucleoside mixture of BrTu (0.5-10 mg/ml) and Tu (1-20 mg/ml) was added no later than 30 min after virus infection, and by the incubation for periods of 2 to 8 h. The cultures "cured" from mengovirus infection were maintained and transferred for several weeks during which they produced neither detectable virus nor visible cytopathogenic effect; however, the infected and "cured" cells themselves were metabolically viable, but impaired in RNA synthesis and unable to devide. With the exception of mengovirus, they also retained capacity to support growth of a variety of viruses (vaccinia, reo, vesicular stomatitis), showing that "cured" cells had retained the metabolic and structural elements needed for virus production. The resistance of "cured" cells to superinfection with mengovirus seems to be attributed to neither interferone action nor destruction or blockade of viral receptors, but probably resulted from the lack of expression of some host factors involved in synthesis of viral RNA or protein.

Izvorni jezik
Engleski

Znanstvena područja
Biologija

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