ライフサイエンスコーパス: VSIV

1 VSIV-GNJ could infect cells at acidic pHs, while the inf

2 VSIV-GNJ infection was also more sensitive to inhibition

3 phenotype by site-directed mutagenesis of a VSIV-GI full-length cDNA and analysis of the recovered e

4 ure at pH 6.8 resulted in the selection of a VSIV-GI variant (VSIV-6.8) that was similar to VSIV-GNJ

5 ferences in pathogenesis between VSIV-GI and VSIV-GNJ.

6 In mice, VSIV-G(NJ) and VSIV-G(NJ)G(I) were attenuated.

7 Anti-EBOV GP1,2 and anti-VSIV N IgG were first detected 10-14 days postvaccinatio

8 Neutralization of infectivity by anti-VSIV G antibodies and inhibition of entry by ammonium ch

9 nts with high accuracy (AUC = 0.965 for anti-VSIV N IgG; AUC = 0.945 for anti-EBOV GP1,2 IgG [P < 0.0

10 and characterize the ISGs that possess anti-VSIV activity.

11 d to the differences in pathogenesis between VSIV-GI and VSIV-GNJ.

12 nse that can potently and specifically block VSIV infection.

13 IV (VSIV-G(I)), VSNJV (VSIV-G(NJ)), or both (VSIV-G(NJ)G(I)), according to the glycoprotein(s) they e

14 were neutralized by antibodies specific for VSIV (VSIV-G(I)), VSNJV (VSIV-G(NJ)), or both (VSIV-G(NJ

15 e and how healthy tissues are protected from VSIV-based therapies, it is crucial that we identify the

16 ined either (i) one copy of the VSIV G gene (VSIV-G(I)); (ii) two copies of the G gene, one from each

17 of the G(NJ) gene instead of the G(I) gene (VSIV-G(NJ)).

18 In order to understand how VSIV causes disease and how healthy tissues are protecte

19 Indeed, just one amino acid substitution in VSIV can govern sensitivity/resistance to TRIM69.

20 f vesicular stomatitis virus (VSV), Indiana (VSIV) and New Jersey (VSNJV).

21 l that we identify the proteins that inhibit VSIV.

22 fied TRIM69 as an ISG that potently inhibits VSIV.

23 therapeutic settings, viral infections like VSIV are sensed by the host, and as a result the host ce

24 e that TRIM69 could be important in limiting VSIV pathogenesis and might influence the specificity an

25 In mice, VSIV-G(NJ) and VSIV-G(NJ)G(I) were attenuated.

26 A further adaptation of VSIV-6.8 to pHs 6.6 and 6.4 resulted in additional amino

27 Sequence analysis of VSIV-6.8 revealed that it had a single amino acid substi

28 el approaches to the rational attenuation of VSIV NV while retaining vector immunogenicity and have l

29 In the case of VSIV, these antiviral proteins constrain viral replicati

30 te and understand the safety and efficacy of VSIV-based therapies.

31 ells at acidic pHs, while the infectivity of VSIV-GI was severely reduced.

32 e that TRIM69 is an IFN-induced inhibitor of VSIV and speculate that TRIM69 could be important in lim

33 Levels of IgG antibodies to EBOV GP1,2 or VSIV N were measured using an enzyme-linked immunosorben

34 J gene was more pathogenic than the parental VSIV-GI virus in swine, a natural host (26).

35 We recovered recombinant VSIVs from engineered cDNAs that contained either (i) on

36 strategies, understanding how ISGs restrict VSIV not only helps in understanding VSIV-induced pathog

37 opies of the G gene, one from each serotype (VSIV-G(NJ)G(I)); or (iii) a single copy of the G(NJ) gen

38 glycoprotein gene from the Indiana serotype (VSIV-GI) or the heterologous glycoprotein gene from the

39 coprotein gene from the New Jersey serotype (VSIV-GNJ).

40 Since VSIV is used as a backbone for multiple oncolytic and va

41 As that contained either (i) one copy of the VSIV G gene (VSIV-G(I)); (ii) two copies of the G gene,

42 in the N and L genes, and by deletion of the VSIV G gene to generate a replicon that is dependent on

43 We applied selective pressure to VSIV-GI by growing it at successively lower pH values an

44 red for entry into the host cell, similar to VSIV virions.

45 IV-GI variant (VSIV-6.8) that was similar to VSIV-GNJ regarding its pH- and ammonium chloride-depende

46 tion in neuropathology compared to wild-type VSIV and the prototypic rVSIV vaccine vector.

47 estrict VSIV not only helps in understanding VSIV-induced pathogenesis but also helps us evaluate and

48 ulted in the selection of a VSIV-GI variant (VSIV-6.8) that was similar to VSIV-GNJ regarding its pH-

49 g of the vesicular stomatitis Indiana virus (VSIV) G protein ecto- and transmembrane domains coupled

50 PORTANCE Vesicular stomatitis Indiana virus (VSIV) is a veterinary pathogen that is also used as a ba

51 Vesicular stomatitis Indiana virus (VSIV), formerly known as vesicular stomatitis virus (VSV

52 vector (vesicular stomatitis Indiana virus [VSIV]) nucleoprotein (N) and the inserted antigen (Ebola

53 ed to higher titers than the parental virus, VSIV-G(I).

54 neutralized by antibodies specific for VSIV (VSIV-G(I)), VSNJV (VSIV-G(NJ)), or both (VSIV-G(NJ)G(I))

55 bodies specific for VSIV (VSIV-G(I)), VSNJV (VSIV-G(NJ)), or both (VSIV-G(NJ)G(I)), according to the