ライフサイエンスコーパス: GALV

1 GALV-like viruses have also been discovered in several S

2 GALV-S and SSAV have the same host range with the except

3 at threonine at 550 inactivates ChoPit1 as a GALV receptor.

4 is sufficient to render PiT2 functional as a GALV receptor.

5 to the woolly monkey virus (WMV), which is a GALV strain that likely originated in a gibbon host.

6 The second record of a GALV in M. burtoni provides further evidence that M. bur

7 The discovery of a GALV in the most western part of the Australo-Papuan dis

8 We hypothesized that vectors with a GALV pseudotype might perform better based on our previo

9 ion were constructed and tested, showing (a) GALV and/or Fcy::Fur expression did not affect virus gro

10 ition in region A can vary without affecting GALV entry.

11 with vectors targeting both amphotropic and GALV receptors may prove to be of additional benefit in

12 xplain previous observations that FeLV-B and GALV, which primarily uses Pit1, display nonreciprocal i

13 cells with equivalent numbers of FeLV-C and GALV or RD114 and GALV-pseudotyped retroviruses for inje

14 le adaptive differences between the KoRV and GALV envelope genes account for differences in their rec

15 Southeast Asian rodent species for KoRV- and GALV-like sequences, using hybridization capture and hig

16 date hosts from Southeast Asia for KoRV- and GALV-like sequences.

17 MLV and GALV RBDs are not able to render FeLV-T infectious.

18 ignificant differences between the RD114 and GALV-pseudotype vectors.

19 lent numbers of FeLV-C and GALV or RD114 and GALV-pseudotyped retroviruses for injection into fetal s

20 lts suggest that fusion-defective FeLV-T and GALV are restricted to homologous RBD rescue of infectiv

21 rus envelope proteins (from Friend virus and GALV or xenotropic viruses) assemble into heteromers whe

22 teins, suggesting that the block to XMRV and GALV infection is mediated at the level of envelope-rece

23 n immunoblot analysis demonstrated that anti-GALV antisera reacted with three proteins in PK-15 cells

24 xtracellular regions of HaPiT2 functioned as GALV receptors.

25 expression did not affect virus growth; (b) GALV expression causes cell fusion and increases the tum

26 o studies involving vectors chimeric between GALV and KoRV-B established that variable regions A and

27 ver, CHOK1 conditioned medium does not block GALV entry into E36, indicating the secreted inhibitors

28 rs, E36 cells are highly susceptible to both GALV and A-MLV in the absence of tunicamycin.

29 ells conferred strong susceptibility to both GALV and A-MLV, and similar overexpression of CHO Pit1 c

30 MMMol cells infected by GALV are resistant to subsequent infection not only by G

31 abolish Pit1-mediated cellular infection by GALV and FeLV-B.

32 these cells are susceptible to infection by GALV.

33 esistant to subsequent infection not only by GALV but also by amphotropic murine leukemia virus.

34 n be trans-activated for infectivity only by GALV RBDs.

35 Surprisingly, transactivation by GALV RBD enabled wild-type or H10A mutant PERVs of all t

36 hips with the other previously characterized GALVs.

37 itive repopulation assay to directly compare GALV-pseudotype retrovirus vectors produced by either Ph

38 have constructed several vectors containing GALV-S/SSAV chimeric envelope proteins to map the region

39 Unlike with E36, GALV and A-MuLV exhibited reciprocal interference when i

40 enerated complete genomic sequences for each GALV strain using hybridization capture and high-through

41 , or +1), and yet Pit1 remained an efficient GALV receptor.

42 viously published ones from highly efficient GALV receptors revealed that every position in region A

43 sera specific for the Gag proteins of either GALV or simian sarcoma-associated virus reacted with the

44 sceptibility of several cell lines to either GALV-S or SSAV infection.

45 extracellular domain of Pit1 is crucial for GALV entry and that an acidic residue at position 550 is

46 , shown by several studies to be crucial for GALV infection.

47 ssed the significance of this difference for GALV infection by replacing the aspartate 550 in Pit1 wi

48 sequence of the critical receptor domain for GALV infection in the Indonesian M. burtoni subsp. was c

49 Whether native ChoPit1 functions for GALV was determined by interference assays using Lec8, a

50 ide domain IV are specifically important for GALV infection.

51 substitution rendered Pit1 nonfunctional for GALV and suggests that threonine at 550 inactivates ChoP

52 Even Pit2 is nonfunctional for GALV only because it has lysine at the first position in

53 s from Wallacea (Indonesia) was positive for GALV.

54 t time that Pit1 is the binding receptor for GALV and not a coreceptor or another type of GALV entry

55 region of Pit2, a nonfunctional receptor for GALV.

56 s, and CHO Pit1 is a functional receptor for GALV.

57 nd ChoPit1 therefore differ as receptors for GALV; ChoPit1 is either inactivated by secreted factors

58 he region of the HaPiT2 protein required for GALV receptor function.

59 his sequence is a definitive requirement for GALV infection has also remained unclear; certain recept

60 ing regions of KoRV that distinguish it from GALV were introduced into the GALV genome, and their fun

61 ent of this transactivation was a functional GALV receptor on the cells.

62 Using dually functional GALV/A-MLV receptors, we examined the role of receptor w

63 d in MDTF, a cell line that lacks functional GALV receptors and is resistant to GALV.

64 en determined for all of the five identified GALV strains, nor has a comprehensive evolutionary analy

65 the genome sequence of this newly identified GALV, the critical domain for infection of its potential

66 Fusion-impaired GALV envelope mutants can be trans-activated for infecti

67 Disruption of this motif in GALV results in vectors with reduced syncytia forming ca

68 Mitochondrial dysfunction occurred in GALV-FMG-induced syncytia prior to loss of viability wit

69 Four of the GALVs, including GALV strain SEATO (GALV-S), were originally isolated fro

70 KoRV's attenuation from a highly infectious GALV-like progenitor virus has allowed the identificatio

71 ugh unable to infect E36 cells, SSAV infects GALV-resistant murine cells expressing the E36-derived v

72 th an insertion C-terminal to the PHQ motif (GALV I(10)) bind Pit1 but fail to infect cells.

73 BHK cells bind neither XMRV nor GALV envelope proteins.

74 yped vector correlated with higher levels of GALV receptor RNA compared with the amphotropic receptor

75 he SSAV SU protein and C-terminal portion of GALV-S fail to infect E36 cells.

76 ubstituted for the corresponding residues of GALV, resulted in vectors exhibiting substantially reduc

77 ly Murinae, may play a role in the spread of GALV-like viruses.

78 provirus very closely related to a strain of GALV.

79 The four strains of GALV isolated from gibbons formed a monophyletic clade t

80 er ERVs, is substantially lower than that of GALV.

81 GALV and not a coreceptor or another type of GALV entry factor.

82 Asia and broadens the known distribution of GALVs in wild rodents.

83 Despite the biomedical utility of GALVs as viral vectors and in cancer gene therapy, full

84 llular domain of MolPit1 and MolPit2 have on GALV receptor function, chimeric receptors were made by

85 g equivalent titers of either amphotropic or GALV pseudotyped vectors containing the neo gene.

86 mposition (e.g., they contain either SSAV or GALV-S envelope protein) to show that the envelope of SS

87 ssing the appropriate receptors bind XMRV or GALV envelope proteins.

88 respectively, can mediate efficient XMRV or GALV infection.

89 ced by fusing BHKXpr1 or BHKPiT1 to XMRV- or GALV-resistant cells, respectively, can mediate efficien

90 raction was cocultivated on irradiated PG13 (GALV-pseudotype) packaging cells for 48 hours.

91 and we evaluated vectors produced by Phoenix-GALV for their ability to transduce hematopoietic progen

92 e engraftment of cells transduced by Phoenix-GALV-pseudotype vectors.

93 In 3 additional baboons we compared Phoenix-GALV-derived vectors to more recently developed lentivir

94 etrovirus vectors produced by either Phoenix-GALV or by the NIH 3T3-derived packaging cell line, PG13

95 ibbon ape leukemia virus pseudotype (Phoenix-GALV), and we evaluated vectors produced by Phoenix-GALV

96 aboon CD34(+) cells, suggesting that Phoenix-GALV-derived oncoretroviral vectors may be even more eff

97 s was significantly higher using the Phoenix-GALV-derived vector as compared with the PG13-derived ve

98 encing, in the attempt to identify potential GALV and KoRV hosts.

99 is exogenous, suggesting that KoRV predates GALV and that gibbons and koalas acquired the virus at d

100 kemia virus hyperfusogenic envelope protein (GALV-FMG) resulted in the formation of multinucleated sy

101 mes identified two highly conserved regions, GALV (residues 309-312) and ESRP (residues 329-332).

102 Incubation with soluble GALV RBD renders GALV I(10) particles infectious, whereas incubation with

103 r of the GALVs, including GALV strain SEATO (GALV-S), were originally isolated from gibbon apes, wher

104 gesting that host immune pressure is shaping GALV evolution.

105 Incubation with soluble GALV RBD renders GALV I(10) particles infectious, wherea

106 Tagged GALV envelope proteins bind specifically to cells expres

107 present at significantly higher levels than GALV-pseudotyped vectors.

108 We have also determined that GALV particles bearing SU proteins with an insertion C-t

109 These results show that GALV-pseudotyped vectors are capable of transducing babo

110 We have previously shown that GALV can infect E36 cells by using both its own receptor

111 This suggests that GALV can enter MMMol via not only the GALV receptor (Mol

112 The GALV-WMV clade in turn formed a sister group to the koal

113 ith concentration in the env gene across the GALV strains that were particularly oncogenic and KoRV s

114 rt here the full genome sequences of all the GALV strains and demonstrate that diversifying selection

115 Although the GALV Env protein is commonly used to make high-titer pse

116 The region has also been proposed to be the GALV binding site, but this lacks empirical support.

117 It is intended to enter the GALV/Fcy::Fur expressing virus into clinical development

118 esis and ITC established that changes in the GALV and ESRP regions affected Phe binding and feedback

119 nguish it from GALV were introduced into the GALV genome, and their functional consequences were asse

120 We propose that region A itself is not the GALV binding motif and that other sequences are required

121 erefore, that the combined expression of the GALV protein and Fcy::Fur provides a highly potent oncol

122 es comprised of the N-terminal region of the GALV-S SU protein and the C-terminal region of SSAV infe

123 s that GALV can enter MMMol via not only the GALV receptor (MolPit1) but also the amphotropic murine

124 rs and 7.1%, 11.3%, <15%, and 26.4% with the GALV pseudotyped vector.

125 The higher gene transfer efficiency with the GALV-pseudotyped vector correlated with higher levels of

126 Four of the GALVs, including GALV strain SEATO (GALV-S), were origin

127 Therefore, GALV and KoRV may have arisen via a cross-species transf

128 sistance of receptor-expressing BHK cells to GALV or XMRV, as shown by tunicamycin treatment and muta

129 overed to date are only distantly related to GALV.

130 unctional GALV receptors and is resistant to GALV.

131 A virus highly similar to GALV has been identified in an Australian native rodent

132 nt with the susceptibility of the species to GALV infection.

133 while Pit2 does not confer susceptibility to GALV.

134 sion of CHO Pit1 conferred susceptibility to GALV.

135 ressing these chimeras became susceptible to GALV, whereas cells expressing wild-type Pit2 remained r

136 ter lung E36 cells, which are susceptible to GALV-S but not SSAV.

137 In this study using GALV-pseudotype vectors, we examined additional variable

138 to infections by gibbon ape leukemia virus (GALV) and amphotropic murine leukemia virus (A-MLV) unle

139 gammaretroviruses gibbon ape leukemia virus (GALV) and feline leukemia virus subgroup B (FeLV-B) can

140 Gibbon ape leukemia virus (GALV) and koala retrovirus (KoRV) most likely originated

141 receptors for the gibbon ape leukemia virus (GALV) and the amphotropic murine leukemia virus (A-MuLV)

142 Gibbon ape leukemia virus (GALV) and the koala retrovirus (KoRV) are very closely r

143 LTR and using the gibbon ape leukemia virus (GALV) Env for internalization were efficient at transduc

144 ogically reactive gibbon ape leukemia virus (GALV) envelope proteins, tagged with a feline leukemia v

145 ve members of the gibbon ape leukemia virus (GALV) family of type C retroviruses.

146 nce implicated in gibbon ape leukemia virus (GALV) infection, and an acidic residue at the first posi

147 d virus (XMRV) or gibbon ape leukemia virus (GALV) infection, even when their respective receptors, X

148 receptor and the gibbon ape leukemia virus (GALV) receptor Pit-1 were used concurrently.

149 e leukemia virus, gibbon ape leukemia virus (GALV), and simian sarcoma-associated virus was demonstra

150 highly infectious gibbon ape leukemia virus (GALV), the infectivity of KoRV, like that of other ERVs,

151 glycoprotein from gibbon ape leukemia virus (GALV), which it was hoped would aid the spread of the ac

152 e cocultivated on gibbon ape leukemia virus (GALV)-based retrovirus vector-producing cells.

153 nd LNX) or by the gibbon ape leukemia virus (GALV)-pseudotype packaging cells PG13 (LNY).

154 ing cells using a gibbon ape leukemia virus (GALV)-pseudotype retroviral vector.

155 tein derived from gibbon ape leukemia virus (GALV).

156 uLVs but also for gibbon ape leukemia virus (GALV).

157 ally resistant to gibbon ape leukemia virus (GALV).

158 ence with that of gibbon ape leukemia virus (GALV).

159 gammaretrovirus, gibbon ape leukemia virus (GALV).

160 able exception is gibbon ape leukemia virus (GALV).

161 D) derived from a gibbon ape leukemia virus (GALV).

162 irus (A-MuLV) and gibbon ape leukemia virus (GALV); E36 cells are highly susceptible to both viruses,

163 The gibbon ape leukemia viruses (GALVs) are among the most medically relevant retroviruse

164 Gibbon ape leukemia viruses (GALVs) are part of a larger group of pathogenic gammaret

165 led a simple retrovirus with a chimeric VL30/GALV-like structure.

166 KoRV is endogenous in koalas, while GALV is exogenous, suggesting that KoRV predates GALV an

167 To determine why GALV cannot infect CHOK1, we cloned and sequenced ChoPit

168 nkey and shares 78% amino acid identity with GALV-S.