ライフサイエンスコーパス: HPIV1

1 HPIV1 and HPIV2 are best known to cause croup while HPIV

2 Human parainfluenza virus type 1 (HPIV1) also causes severe pediatric respiratory illness,

3 version of human parainfluenza virus type 1 (HPIV1) bearing a stabilized attenuating mutation in the

4 Human parainfluenza virus type 1 (HPIV1) is a significant cause of pediatric respiratory d

5 Human parainfluenza virus type 1 (HPIV1) is a significant cause of respiratory tract disea

6 Human parainfluenza virus type 1 (HPIV1) is an important respiratory pathogen in children

7 Human parainfluenza virus type 1 (HPIV1) is an important respiratory pathogen in young chi

8 (RSV) and human parainfluenza virus type 1 (HPIV1) to HPIV4 infect virtually all children by the age

9 imens (8 of 10 positive for HPIV serotype 1 [HPIV1], 9 of 10 positive for HPIV2, and 9 of 10 positive

10 V); human parainfluenza viruses 1, 2, and 3 (HPIV1, -2, and -3, respectively); and influenza A and B

11 (IFN) is induced following infection with an HPIV1 mutant expressing defective C proteins with an F17

12 nal antibodies, one targeting both HPIV3 and HPIV1 and the other targeting both RSV and HMPV.

13 nd immunogenic against the RSV F protein and HPIV1 in the hamster model and provided substantial prot

14 not express any of the four C proteins, and HPIV1-C(F170S), a less attenuated mutant that contains a

15 ranasal pediatric vaccine.IMPORTANCE RSV and HPIV1 are major viral causes of acute pediatric respirat

16 o provide a bivalent vaccine against RSV and HPIV1.

17 e pre-N position was immunogenic for RSV and HPIV1.

18 rapidly identifying mutations that attenuate HPIV1 and for generating live-attenuated HPIV1 vaccine c

19 In the present study, we sought to attenuate HPIV1 by the importation of one or more known attenuatin

20 Two recently characterized live attenuated HPIV1 vaccine candidates expressing mutant C proteins we

21 ate HPIV1 and for generating live-attenuated HPIV1 vaccine candidates.

22 r genes that otherwise would be repressed by HPIV1 infection.

23 We similarly evaluated HPIV1-P(C-), a highly attenuated and apoptosis-inducing

24 tion is compromised, as in the case of F170S HPIV1, the resulting PKR activation and reduction in vir

25 meric form with its TMCT domain derived from HPIV1 F.

26 ous paramyxoviruses into homologous sites in HPIV1.

27 The RSV F gene was engineered to include HPIV1 transcription signals and inserted individually in

28 xoviruses including respiroviruses (that is, HPIV1 and HPIV3) and morbilliviruses (that is, MeV).

29 the anti-IFN and antiapoptotic activities of HPIV1 had additive effects on attenuation in vivo.

30 the anti-IFN and antiapoptosis activities of HPIV1 were separable: both activities are disabled in rH

31 er Sendai viruses (the murine counterpart of HPIV1) to noninvasively measure primary infection, immun

32 as a tool for the preclinical evaluation of HPIV1 vaccines, although how these in vitro data will co

33 Thus, the C proteins of HPIV1 are nonessential but have anti-IFN and antiapoptos

34 Mutation or deletion of the C proteins of HPIV1 permitted the activation of over 2,000 cellular ge

35 ail (TMCT) domains substituted with those of HPIV1 F in an effort to direct packaging in the vector p

36 V), and human parainfluenza virus types one (HPIV1) and three (HPIV3) can cause severe disease and de

37 Recombinant HPIV1 (rHPIV1) mutants bearing a single imported mutatio

38 ent RSV/HPIV1 vaccine based on a recombinant HPIV1 vector, attenuated by a stabilized mutation, that

39 he preclinical development of a bivalent RSV/HPIV1 vaccine based on a recombinant HPIV1 vector, atten

40 actions, was used in this study to show that HPIV1 selectively infects ciliated cells within the HAE

41 Cellular pathways targeted by the HPIV1 C proteins were identified and their transcription

42 gmentation in LLC-MK2 cells, identifying the HPIV1 C proteins as inhibitors of apoptosis.

43 were ablated by a F170S substitution in the HPIV1 C proteins (F170S) or by silencing the C open read

44 Unmodified EBOV GP was packaged into the HPIV1 particle, and the TMCT modification did not increa

45 MCT) domains were replaced with those of the HPIV1 F protein in an effort to enhance packaging into t

46 us titer, supporting the hypothesis that the HPIV1 C proteins are critical for the inhibition of the

47 Thus, the HPIV1 C proteins normally limit the accumulation of dsRN

48 s the response of human respiratory cells to HPIV1 infection.

49 , but not following infection with wild-type HPIV1.

50 d were resistant to challenge with wild-type HPIV1.

51 ns a single point mutation in C and, like wt HPIV1, does not efficiently induce apoptosis, to examine

52 Infection with either mutant, but not WT HPIV1, induced a significant accumulation of intracellul

53 proteins was reduced compared to that of WT HPIV1.

54 V1-P(C-) protected against challenge with wt HPIV1, its highly restricted replication in AGMs and in

55 ssion kinetics to examine how wild-type (wt) HPIV1 infection altered gene expression in human respira

56 We found that infection with wild-type (WT) HPIV1 suppressed the innate immune response in human air

57 replicated as efficiently as wild-type (wt) HPIV1, but its titer subsequently decreased coincident w

58 he same as the final titer of wild-type (wt) HPIV1.