Disease relevance of Leukemia Virus, Gibbon Ape

• Feline leukemia virus subgroup B (FeLV-B) and gibbon ape leukemia virus (GALV) utilize the human protein Pit1 but not the related protein, Pit2, as receptor [1].
• In contrast, without prestimulation of the target cells, a human immunodeficiency virus type 1 (HIV-1)-based lentiviral vector pseudotyped with gibbon ape leukemia virus envelope (GALV Env) was nearly as inefficient as murine leukemia virus (MLV)-based oncoretroviral vectors in transducing NOD/SCID repopulating cells [2].
• The glioma cell lines U87, U118, and U251 previously characterized by zymography and MMP-2 activity assay as high, medium, and low MMP expressors, respectively; normal human astrocytes and the MMP-poor cell line TE671 were transfected with the GALV, GALV N40, GALV X40, and GALV M40 constructs [3].
• METHODS: Replication-defective adenoviruses (Ad) were constructed expressing the hyperfusogenic version of the GALV glycoprotein linked to a blocking ligand (C-terminal extracellular domain of CD40 ligand) through either an MMP-cleavable linker (AdM40) or a non-cleavable linker (AdN40) [4].
• A recombinant Gibbon ape leukemia virus (GALV), containing a gene encoding Escherichia coli beta-galactosidase was next introduced into 24 hr obstructed bile ducts [5].

High impact information on Leukemia Virus, Gibbon Ape

• The higher gene transfer efficiency with the GALV-pseudotyped vector correlated with higher levels of GALV receptor RNA compared with the amphotropic receptor in CD34(+) hematopoietic cells [6].
• In addition, the GALV M40 construct retained its cytotoxic activity against U87 cells in vivo, although less effectively as compared to unmodified GALV [3].
• Expression constructs were made expressing the hyperfusogenic version of the Gibbon Ape Leukemia Virus envelope glycoprotein (GALV) linked to a blocking ligand (the C-terminal extracellular domain of CD40 ligand) via either an MMP cleavable linker (GALV M40), a factor Xa protease cleavable linker (GALV X40), or a noncleavable linker (GALV N40) [3].
• Here we describe heat-directed targeting of an activated form of the Gibbon ape leukemia virus env protein (GALV FMG) to tumor cells [7].
• A highly polymorphic nine-residue sequence within Pit1, designated region A, has been proposed as the virus binding site, because mutations in this region abolish Pit1-mediated cellular infection by GALV and FeLV-B [8].

Chemical compound and disease context of Leukemia Virus, Gibbon Ape

• Even Pit2 is nonfunctional for GALV only because it has lysine at the first position in its region A, which is otherwise highly diverse from region A of Pit1 [9].
• This single substitution rendered Pit1 nonfunctional for GALV and suggests that threonine at 550 inactivates ChoPit1 as a GALV receptor [10].
• METHODS: We generated GALV envelope expression constructs displaying EGF or GM-CSF blocking ligands at the N-terminus of GALV envelope SU via a non-cleavable, Factor Xa protease or MMP-cleavable linker and investigated their cytotoxicity on MMP-positive and negative cell lines [11].

Biological context of Leukemia Virus, Gibbon Ape

• Strikingly, the amino acid sequence of the fourth extracellular loop, which is critical for GALV surface glycoprotein binding, has complete identity between the human and feline PiT-1s, while the mouse PiT-1, non-functional for GALV entry, is quite divergent [12].

Anatomical context of Leukemia Virus, Gibbon Ape

• We then analyzed whether this enhanced expression of GLVR-1 correlated with increased infectivity of lymphocytes by retroviral vectors that utilize the GALV envelope compared to those that use the amphotropic envelope [13].
• We have found that retroviral vectors packaged in ecotropic, amphotropic, and gibbon ape leukemia virus (GALV) envelope proteins were all inactivated by human sera, and human sera also lysed mouse NIH-3T3 cells and the retroviral vector packaging cells derived from them [14].

Gene context of Leukemia Virus, Gibbon Ape

• Furthermore, we have constructed Ram-1/Glvr-1 hybrid receptors that allow entry of both GALV and amphotropic virus [15].
• This suggests that GALV can enter MMMol via not only the GALV receptor (MolPit1) but also the amphotropic murine leukemia virus receptor (MolPit2) [16].
• We have now determined that the substitution of a single amino acid residue, glutamic acid, for the lysine residue at position 522 in the fourth extracellular region of the PiT2 protein is sufficient to render PiT2 functional as a GALV receptor [17].
• Earlier studies have shown that a stretch of nine residues (position 550 to 558) in the fourth extracellular domain of Pit1 is crucial for GALV entry and that an acidic residue at position 550 is indispensable [16].
• Expression of a human-rat chimeric GLVR1 in murine cells demonstrated that rat GLVR1 could function as a receptor for GALV and SSAV but not for FeLV-B [18].

Analytical, diagnostic and therapeutic context of Leukemia Virus, Gibbon Ape

• Southern blot hybridization with GALV-derived env and pol-env probes failed to detect any homology between GALV and M813, but did show that all mouse species tested carry numerous copies of GALV-related sequences [19].

References