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Example sentences for: nnr
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Moreover, the functional viral RdRP, as detailed later for RSV, is a complex holoenzyme composed of viral as well as cellular proteins [ 17 18 19 20 21 22 23 ] . Second, many NNR viral genomes and proteins are currently expressed from vaccinia-based cDNA clones, which generally requires superinfection by vaccinia virus [ 22 23 ] . Unfortunately, vaccinia virus itself is a major modulator of cellular signaling, including MAP kinase pathways and the actin cytoskeleton [ 24 25 26 ] . It is, therefore, virtually impossible to study the interaction between cellular signaling pathways and NNR viruses in cells that are also superinfected by vaccinia virus [ 24 25 26 ] . Third, mutations in the recombinant DNA are "permanent", and thus, the mutational phenotype cannot be switched on at pre-determined time points in infection.
As described earlier (in the beginning of the Results section), intracellular NNR viral replication generates both negative- and positive-strand full-length genomic RNA, each of which should find complementarity to the appropriate strand of the anti-F dsRNA.
As mentioned before, the N-encapsidated genome-length RNAs are indeed extremely resistant to nucleases, to the extent that formation of such nuclease-resistant RNA products is in fact considered a defining criterion for viral replication in vitro and in vivo [ 32 ] . While the resistance of the viral genomic RNA to dsRNA has important ramifications for antiviral therapy, it is also clear that the dsRNA approach cannot be used against cis -acting NNR viral genomic sequences such as the intergenic regions, for which the cDNA-based approach will continue to be the method of choice [ 16 ] . It is obvious that a creative combination of the two techniques will lead to exciting possibilities in the reverse genetics of RNA viruses and in the antiviral regimen.
The RNA genome of RSV is about 15 kb long and contains 11 documented protein-coding genes [ 13 ] . Three viral proteins are minimally required to reconstitute the functional transcription complex of NNR viruses [ 3 ] : the nucleocapsid protein (N) that wraps the negative-strand genome RNA and its full-length complement, the positive-strand antigenome RNA, thus converting them into highly nuclease-resistant, chromatin-like templates; the large protein (L), which is the major subunit of the RdRP; and the phosphoprotein (P), which is the smaller subunit of RdRP and an essential transcription factor of L [ 19 20 21 22 ] . In RSV, optimal transcription, although not replication, additionally requires the transcription antitermination protein M2-1 [ 13 ] . In addition, cellular actin, and to a lesser extent, profilin, are also required for viral transcription [ 17 18 ] .
We speculate that the genomic and antigenomic RNA of NNR viruses escape the onslaught of dsRNA because they are tightly wrapped with the nucleocapsid protein N, which makes them inaccessible to the dsRNA and/or the RNAi silencing complex (RISC).
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