Disease relevance of A18R

• Prior phenotypic analysis of a vaccinia virus gene A18R mutant, Cts23, showed the synthesis of longer than wild type (Wt) length viral transcripts during the intermediate stage of infection, indicating that the A18R protein may act as a negative transcription elongation factor [1].
• Vaccinia virions containing mutant A18R gene product are defective in early viral transcription in vitro, and infection with A18R mutant virus results in aberrant viral transcription late during infection [2].

High impact information on A18R

• Therefore, we conclude that A18R and an as yet unidentified cellular factor(s) are required for the in vitro release of nascent RNA from a vaccinia virus transcription elongation complex [1].
• By itself, purified polyhistidine-tagged A18R protein (His-A18R) was unable to induce release; however, release did occur in the presence of purified His-A18R protein plus extract from either Cts23 or mock-infected cells [1].
• These results demonstrate that the A18R gene product is a negative transcription elongation factor for postreplicative viral genes [3].
• The results show that mutation of the A18R gene results in increased readthrough transcription of the M1L gene originating from the K2L intermediate promoter [3].
• The loss of A18R protein function results in unregulated transcription late during virus infection from regions of the viral genome which are normally transcriptionally quiescent [4].

Biological context of A18R

• The phenotype of A18R ts mutants is indistinguishable from that of wild-type infections done in the presence of isatin-beta-thiosemicarbazone (IBT) [5].
• At late times postinfection, A18R mutant-infected cells contained an increased amount of complementary RNA and a higher steady state level of RNA from regions of the genome transcribed normally only early in the infection [5].

Associations of A18R with chemical compounds

• Previous experiments with the antipoxviral drug isatin-beta-thiosemicarbazone suggest that lethal mutation of gene G2R would compensate for mutations in gene A18R [6].

Other interactions of A18R

• Characterization of the interactions among vaccinia virus transcription factors G2R, A18R, and H5R [7].

Analytical, diagnostic and therapeutic context of A18R

• We have used an electrophoretic gel mobility shift assay to show that the A18R protein forms a stable complex with single-stranded DNA, and to a lesser extent RNA, in a reaction that does not require ATP [8].

References