Author: Adriaan H. de Wilde; A. Linda Boomaars-van der Zanden; Anja W. M. de Jong; Montserrat Barcéna; Eric J. Snijder; Clara C. Posthuma
Title: Inhibition of arterivirus RNA synthesis by cyclophilin inhibitors is counteracted by mutations in replicase transmembrane subunits Document date: 2019_3_24
ID: l5n30kbm_5
Snippet: The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. . https://doi.org/10.1101/587261 doi: bioRxiv preprint concentration, titers of above 10 4 PFU/ml (EAV CsA-1 and CsA-3) or even around 10 6 PFU/ml (EAV 255 CsA-2) were reached when infection was done with the P7 viruses from the three CsA-resistant 256 lineages. Similar results were obtained in BHK-21 cells, albeit that the yields of all three lineages .....
Document: The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. . https://doi.org/10.1101/587261 doi: bioRxiv preprint concentration, titers of above 10 4 PFU/ml (EAV CsA-1 and CsA-3) or even around 10 6 PFU/ml (EAV 255 CsA-2) were reached when infection was done with the P7 viruses from the three CsA-resistant 256 lineages. Similar results were obtained in BHK-21 cells, albeit that the yields of all three lineages were 257 equally reduced compared to wtEAV-P7 in this cell line (data not shown). 258 259 Most CsA resistance-associated mutations map to EAV nsp5. In order to identify CsA resistance-260 associated mutations, the consensus genome sequence of the three P7 CsA-resistant EAV samples was 261 determined following RT-PCR amplification (Table 2 and Fig. 1A ). The EAV CsA-1 consensus 262 sequence contained three mutations, all mapping to the nsp5-coding region of ORF1a and resulting in 263 three amino acids substitutions: Q21R (mixed with the wt sequence), Y113H, and A134V. 264
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