ライフサイエンスコーパス: EEEV

1 EEEV efficiently utilizes both the VEEV-specific FXR pro

2 ine elicited neutralizing antibodies against EEEV and protected against aerosol exposure to a North A

3 lpha/beta induction in vivo, which may allow EEEV to evade the host's innate immune responses and the

4 is new study demonstrate that North American EEEV exhibits a high level of redundancy in using host f

5 haviruses, can cause fatal encephalitis, and EEEV is a select agent of concern in biodefense.

6 ine encephalitis virus (WEEV) from SINV- and EEEV-like ancestors.

7 ately 35-amino-acid-long peptide of VEEV and EEEV capsid proteins plays the most critical role in the

8 nses and protected mice from lethal VEEV and EEEV challenges at 1 month postvaccination as well as le

9 single-dose protection from lethal VEEV and EEEV challenges, demonstrating the potential for a multi

10 est that the New World alphaviruses VEEV and EEEV developed an alternative mechanism of transcription

11 ure of rISFV vectors expressing the VEEV and EEEV E2/E1 glycoproteins also provided durable, single-d

12 attenuate virulence and express the VEEV and EEEV E2/E1 surface glycoproteins as vaccine antigens.

13 ainst the encephalitic alphaviruses VEEV and EEEV, both of which can cause fatal disease.

14 es of attenuated vaccine strains of VEEV and EEEV.

15 Finally, when cell lines containing EEEV replicons encoding capsid were selected, replicons

16 In contrast, EEEV replicates poorly in lymphoid tissues, preferential

17 the EEEV HS binding domain may arise during EEEV sylvatic cycles and that this variation may influen

18 ruses, including Venezuelan (VEEV), eastern (EEEV), and western equine encephalitis viruses, constitu

19 This region is also critical for EEEV pathogenesis.

20 functioning in transcription inhibition from EEEV-like virus.

21 In hamsters, EEEV replicates in visceral organs, produces viremia, an

22 To determine how EEEV may evade innate immune responses, we screened indi

23 Other identified EEEV nsP3 HVD-interacting host proteins are also capable

24 ied HVD-binding factors are also involved in EEEV replication, but their roles are not as critical as

25 RNAs, we found that translation of incoming EEEV genomes was almost completely inhibited in myeloid,

26 ate immune responses, we screened individual EEEV proteins for the ability to rescue the growth of a

27 f the capsid were introduced into infectious EEEV, the mutants exhibited delayed replication in Vero

28 After infection with most EEEV strains, higher viremia levels and shorter survival

29 es: one that circulates in North America (NA EEEV) and the Caribbean and three that circulate in Cent

30 s lower and more consistent than that for NA EEEV (2.7 x 10(-4)), which exhibited considerable rate v

31 The single, monophyletic NA EEEV lineage exhibited mainly temporally associated rela

32 rames of all available SA EEEV and recent NA EEEV isolates were sequenced and used in evolutionary an

33 ed in the brain, liver, and muscle of the NA EEEV-infected animals at the time of euthanasia or death

34 rain lesions described for human EEE, the NA EEEV-infected animals developed meningoencephalitis in t

35 The NA EEEV-infected animals either died or were euthanized on

36 ut there was no detectable viremia in the NA EEEV-infected animals.

37 Unlike many alphaviruses, NA-EEEV infection of mice yields limited signs of febrile i

38 of HS receptors by naturally circulating NA-EEEV strains.

39 ivation of the major HS binding domain in NA-EEEV E2 demonstrated that the HS binding increased brain

40 We propose that HS binding by natural NA-EEEV strains alters tropism in vivo to antagonize/evade

41 d the extreme neurovirulence of wild-type NA-EEEV may be a consequence.

42 We demonstrate that wild-type NA-EEEV strain FL91-4679 uses HS as an attachment receptor

43 erican eastern equine encephalitis virus (NA-EEEV) is uniquely neurovirulent among encephalitic alpha

44 erican eastern equine encephalitis virus (NA-EEEV) isolates and demonstrated that naturally circulati

45 primary HS binding site of wild-type (WT) NA-EEEV viruses.

46 similar to those described in human cases of EEEV.

47 Here, we demonstrate that infectivity of EEEV for myeloid lineage cells including DCs and macroph

48 ic health threat, the molecular mechanism of EEEV replication and interaction with hosts is poorly un

49 es and altered virulence in a mouse model of EEEV disease.

50 contributes to the extreme neurovirulence of EEEV.

51 ost gene expression and to the protection of EEEV from the antiviral effects of IFNs.

52 usly demonstrated that the capsid protein of EEEV is a potent inhibitor of host cell gene expression

53 tified a region within the capsid protein of EEEV that contributes to the inhibition of host gene exp

54 the exceptionally high replication rates of EEEV and suggest a new means of its attenuation and new

55 ot affect vRC formation; however, removal of EEEV's ability to interact with both protein families ha

56 explanation for the efficient replication of EEEV and may contribute to its highly pathogenic phenoty

57 nce receptor interaction and the severity of EEEV disease.

58 North American and South American strains of EEEV produce neurologic disease that resembles that asso

59 The altered tropism of EEEV correlated with an almost complete avoidance of ser

60 In this regard, the tropisms of EEEV and VEEV differ dramatically, likely contributing t

61 osol exposure to a North American variety of EEEV.

62 al and nonstructural protein gene regions on EEEV virulence.

63 ous or aerosol challenge with VEEV, WEEV, or EEEV was demonstrated out to 12 months after vaccination

64 t inhibition of genome translation restricts EEEV infectivity for myeloid but not mesenchymal lineage

65 iological evidence that some, if not all, SA EEEV strains are attenuated for humans.

66 t circulate in Central and South America (SA EEEV).

67 city and ecology, and propose that NA and SA EEEV be reclassified as distinct species in the EEE comp

68 ding upon the sequences used, with NA and SA EEEV diverging ca. 922 to 4,856 years ago and the two ma

69 divergences between members of the NA and SA EEEV lineages, consistent with major differences in path

70 tein open reading frames of all available SA EEEV and recent NA EEEV isolates were sequenced and used

71 In contrast, SA EEEV comprised three divergent lineages, two consisting

72 nucleotide substitution rate per year for SA EEEV (1.2 x 10(-4)) was lower and more consistent than t

73 . 922 to 4,856 years ago and the two main SA EEEV lineages diverging ca. 577 to 2,927 years ago.

74 A phylogenetic comparison of SA EEEV and Venezuelan equine encephalitis viruses (VEEV) d

75 The SA EEEV-infected animals developed peak viremia titers of 2

76 to anorexia and neurologic signs, but the SA EEEV-infected animals remained healthy and survived.

77 An analysis of stable EEEV replicons expressing mutant capsid proteins corrobo

78 describe use of the golden hamster to study EEEV-induced acute vasculitis and encephalitis.

79 host proteins are also capable of supporting EEEV replication, albeit with a dramatically lower effic

80 Our new study demonstrates that EEEV exhibits a unique level of redundancy in the use of

81 ese observations in vivo, demonstrating that EEEV is compromised in its ability to replicate within l

82 We determined that EEEV infection of myeloid lineage cells was restricted a

83 esults suggest that natural variation in the EEEV HS binding domain may arise during EEEV sylvatic cy

84 Only expression of the EEEV capsid facilitated NDV-GFP replication.

85 An electrostatic map of the EEEV E1/E2 heterotrimer based upon the recent Chikunguny

86 The hypervariable domain of the EEEV nsP3 protein interacts with all of the members of t

87 Similarly, the EEEV replicon and V/W/E combination vaccine elicited neu

88 roduces 10-fold higher viremia than virulent EEEV strains.

89 Eastern equine encephalitis virus (EEEV) causes human encephalitis in North America (NA), b

90 Eastern equine encephalitis virus (EEEV) causes sporadic but often severe cases of human an

91 Eastern equine encephalitis virus (EEEV) causes sporadic epidemics of human and equine dise

92 Eastern equine encephalitis virus (EEEV) is a human and veterinary pathogen that causes spo

93 Eastern equine encephalitis virus (EEEV) is a representative member of the New World alphav

94 MPORTANCE Eastern equine encephalitis virus (EEEV) is one of the most pathogenic New World alphavirus

95 Eastern equine encephalitis virus (EEEV) produces the most severe human arboviral disease i

96 Eastern equine encephalitis virus (EEEV) produces the most severe human arboviral diseases

97 WEEV), or eastern equine encephalitis virus (EEEV) when given individually or in combination (V/W/E)

98 s (VEEV), eastern equine encephalitis virus (EEEV), and western equine encephalitis virus (WEEV) are

99 VEEV) and eastern equine encephalitis virus (EEEV), evolved separately from those of the Old World, i

100 WEEV) and eastern equine encephalitis virus (EEEV), two New World alphaviruses, can cause fatal encep

101 VEEV) and Eastern equine encephalitis virus (EEEV), which have demonstrated potential for natural dis

102 EEV), and eastern equine encephalitis virus (EEEV).

103 viruses (Eastern equine encephalitis virus [EEEV], Western equine encephalitis virus [WEEV], Venezue

104 and Venezuelan equine encephalitis viruses (EEEV and VEEV, respectively) cause severe morbidity and

105 for a variety of vertebrate hosts, in which EEEV induces a highly debilitating disease, and the outc

106 ng intranasal or subcutaneous challenge with EEEV.