modified dye uptake assay including formazan test EC 90 not tested plaque reduction assay

Transcription

1 Sauerbrei A, Bohn-Wippert K, Kaspar M, Krumbholz A, Karrasch M, Zell R Database on natural polymorphisms and resistance-related non-synonymous mutations in thymidine kinase and DNA polymerase genes of herpes simplex virus types 1 and 2. J Antimicrob Chemother 71:6-16, doi: /jac/dkv285, PMID: Supplementary Table 7: Resistance-associated aa changes in DNA pol gene of HSV-1 including nt changes, their location, antivirals tested as well as, methods for phenotypic testing and references. Amino acid change Nucleotide change Drug susceptibility Antivirals tested ( ratio of resistant to sensitive viral isolate or value) Domain Test methods for phenotype References Aciclovir Brivudin Penciclovir Foscarnet Cidofovir resistant sensitive (ACV) (BVDU) () () () L187stop deletion (C) nt 301 (pre NH 2-terminal, >35.5 µm >35.2 µm >32.0 µm µm 4.4 µm modified dye uptake assay including formazan test D368A* A1103C Exo I ACV, I529M A1587G delta- C ACV BVDU 10.0x 1.3x plaque reduction assay K532T A1595C delta- C ACV µm <660.0 µm plaque reduction assay E545D A1635T/C delta- C ACV, BVDU x 1.3x plaque reduction assay Y557S* T1669A/ A1670G delta- C ACV, phosphonoacetic acid (PAA) - not given not given, mice in vivo assay Q570R C1708A/ A1709G delta- C ACV 7.1 µm 28.2 µm yield reduction assay (enzyme linked virus inhibitory reporter assay - ELRA) V573M* G1717A Exo ACV, 0.1 µm 6.9 µm 8.5 µm mice in vivo assay

2 D581A** A1742C Exo phosphonoacetic acid (PAA) µm L583V C1747G Exo ACV µm <660.0 µm E597D* G1790T delta- C ACV, PAA x 8.0x plaque reduction assay A605V* C1814T delta- C ACV,, 35.0 µm 12.4 µm >660.0 µm 2.6 µm plaque reduction assay Y608stop insertion (G) nt 1788 delta- C ACV - >25.0 µm crystal structure modeling Q618H* G1854T/C delta- C ACV BVDU,, 0.6 µm µm µm 0.4 µm plaque reduction assay V621S G1861A/ T1862G delta- C ACV µm crystal structure modeling A657T G1969A, >35.5 µm 9.7 µm >32.0 µm 61.1 µm 1.5 µm modified dye uptake assay including formazan test R700G* A2098G II ACV, 2.0x not given 6.0x R700M** G2099T II ACV, 0.06 µm 0.4x 27.4 µm 7.8 µm

3 L702H T2105A II 35.5 µm µm 6.0 µm 0.3 µm plaque reduction assay L702P T2105C II ACV, BVDU x >257.0x plaque reduction assay V714M* T2140A II ACV, BVDU, 0.2 µm 0.01 µm µm 0.5 µm plaque reduction assay V715G T2144G II >443.8 µm µm 0.04 µm plaque reduction assay V715M G2143A II ACV, 12.7 µm 42.7 µm 0.02 µm plaque reduction assay F716L C2148A/G II ACV, 1.8x 2.9x 2.9x plaque reduction assay A719T G2155A II ACV, 5.9x 2.2x 1.9x plaque reduction assay A719V C2156T II, >35.5 µm >35.2 µm 32.0 µm µm 1.9 µm plaque reduction assay including formazan test, dye uptake assay, DNA reduction assay S724N G2171A II, BVDU 0.4 µm 9.6 µm >422.4 µm plaque reduction assay including formazan test, yield reduction assay (ELRA) DNA reduction assay S725G A2173G II - >660.0 µm plaque reduction assay

4 F733C T2198G II ACV >10.0 µm µm plaque reduction assay E771Q G2311C ACV >443.8 µm <660.0 µm plaque reduction assay L774F* C2320T ACV, - 3.7x 3.2x DNA reduction assay, denaturing gradient gel electrophoresis, S775N G2324A ACV >10.0 µm 27.0 µm plaque reduction assay L778M C2332A - 5.5x 2.0x 2.0x plaque reduction assay D780N G2338A ACV, 6.1x 2.2x 1.2x plaque reduction assay W781V* T2341G G2342T ACV, x 3.0x plaque reduction assay L782I C2344A ACV, 6.4x 2.3x 1.8x plaque reduction assay P797T* C2389A ACV, PAA - not given not given plaque reduction assay E798K G2392A ACV,, BVDU, µm µm µm µm 3.0 µm plaque reduction assay

5 L802F* C2404T BVDU 0.6 µm 0.02 µm µm 0.6 µm plaque reduction assay V813M* G2437A ACV,, - 5.0x 3.0x 4.0x plaque reduction assay N815S** A2444G ACV, BVDU,, 16.2 µm <0.2 µm >31.6 µm 24.8 µm 1.9 µm plaque reduction assay Y818C* A2453G ACV,,, BVDU 31.1 µm 0.2 µm 6.0 µm 2.1 µm plaque reduction assay T821M C2462T ACV, BVDU 6.3x 0.2x 2.1x G841C* G2521T ACV,,, µm 20.0 µm > µm 7.4 µm plaque reduction assay G841S G2521A ACV PAA 29.0x 2.6x plaque reduction assay R842S* C2524A ACV, - 150x 4x plaque reduction assay M880T T2639C I ACV BVDU 10.0x 1.3x plaque reduction assay S889A* T2665G I ACV, PAA x 225.0x

6 F891C** T2672G I ACV,, 10.0x 2.0x 10.0x 1.7x F891Y* T2672A I ACV, PAA µm plaque reduction assay V892M* G2674A I ACV, PAA µm plaque reduction assay G901V G2702T I ACV 15.0 µm not given modified dye uptake assay including formazan test D907V A2720T ACV, 3.8x 2.3x 1.6x cell growth assay I922N* T2765A µm 0.74 µm plaque reduction assay Y941H T2821C I ACV, - 9.4x 0.4x V958L* G2872C V (thumb >27.5 µm 17.2 µm >660.0 µm 4.1 µm plaque reduction assay R959H* G2876A V (thumb BVDU 0.3 µm 0.21 µm µm 0.5 µm plaque reduction assay K960R* A2879G V (thumb 0.2 µm 0.08 µm 22.9 µm 2.3 µm plaque reduction assay

7 V N961K** C2883G/A (thumb ACV,, 5.3x not given 0.8x 1.4x W998L* G2993T (thumb ACV, BVDU, 0.1 µm 0.01 µm 35.0 µm 1.6 µm plaque reduction assay I1028T T3083C (thumb BVDU 0.03 µm 1.9 µm D1070N* G3208A (thumb ACV, BVDU, 61.0x 0.1x 2.7x mice in vivo assay H1228D C3682G (thumb ACV - >25.0 µm crystal structure modeling