ライフサイエンスコーパス: ISDR

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1 rapy was associated with measurable HVR1 and ISDR mutation in nine of nine (100%) and two of nine (22

2 Introduction of multiple ISDR mutations abrogated the ability of NS5A to bind to

3 We observed that the NS5A ISDR, though necessary, was not sufficient for PKR inter

4 5A-mediated PKR regulation and the effect of ISDR mutations on this regulatory process.

5 e effects may be independent of the putative ISDR.

6 onse using sequences outside of the putative ISDR.

7 onsensus IFN sensitivity-determining region (ISDR(237-276)) sequence associated with IFN resistance w

8 n interferon sensitivity determining region (ISDR) deletion mutant (NS5A-1a-triangle upISDR) isolated

9 rferon (IFN) sensitivity-determining region (ISDR) of the hepatitis C virus (HCV) NS5A protein is con

10 putative IFN sensitivity-determining region (ISDR) of the nonstructural NS5A gene were analyzed by he

11 e interferon sensitivity-determining region (ISDR) of the NS5A protein in wild-type HCV-N drastically

12 e interferon sensitivity-determining region (ISDR), are associated with sensitivity of HCV to the ant

13 rferon (IFN) sensitivity determining region (ISDR).

14 Evolution to IFN-resistant ISDR sequences was observed in only one of nine IFN-trea

15 of fixation of mutations was observed in the ISDR for IFN-treated patients than for untreated control

16 ions in the 26 amino acids downstream of the ISDR required for PKR binding in pretreatment isolates f

17 Independent of the ISDR, IFN-alpha rapidly inhibited HCV RNA replication in

18 e HCV envelope region, while pressure on the ISDR was evident in only a subset of patients.

19 ditional 26 amino acids (aa) carboxyl to the ISDR were required for NS5A-PKR complex formation.

20 esponders but not nonresponders, whereas the ISDR and PKR binding domains did not change in either pa

21 although the presence of Ala(245) within the ISDR was associated with nonresponse to treatment in gen

22 g region of NS5A, including those within the ISDR, can disrupt the NS5A-PKR interaction, possibly ren

23 y, this study attempted to determine whether ISDR amino acid mutation number would correlate better w

24 treated with high-dose IFN was compared with ISDR mutation number.

25 patocyte death rate correlated directly with ISDR mutation number (P=.01).

26 e viral log decline correlated directly with ISDR mutation number (P=.02).

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