A human amphotropic retrovirus receptor is a second member of the gibbon ape leukemia virus receptor family.

Zeijl, Marja van; Johann, S V; Closs, Ellen I.; Cunningham, James M.; Eddy, Roger L.; Shows, Thomas B.; O’Hara, Brian J.

doi:10.1073/pnas.91.3.1168

Cited by 249 publications

(243 citation statements)

References 37 publications

Supporting

Mentioning

234

Contrasting

Order By: Relevance

“…Accordingly, while the lack of Env prevented HIV1 from causing CD4 þ T-cell death, pseudotyped HIV1 particles expressing the MuLV amphotropic Env induced CD4 þ T-cell killing in the presence of cellular factors released by dying cells. Because the amphotropic Env of MuLV allows entry into cells through a high-affinity Na þ -dependent phosphate transporter, 43,44 our results imply that neither HIV1 gp120 Env interaction with CD4 and/or CXCR4, nor HIV1 gp41 Env-mediated fusion is required for the induction of CD4 þ T-cell death in our in vitro model. Our findings also indicate that the Nef protein, present in small amounts in the HIV1 particles 45 and reported to either induce or repress cell death, [46][47][48][49] is not required for the killing of noncycling CD4 þ T cells in our model.…”

Section: Discussionmentioning

confidence: 73%

“…To discriminate between these possibilities, we decided to investigate the effect of chimeric X4-tropic NL4-3 viruses obtained by pseudotyping the HIV env with the amphotropic env of another retrovirus, the MuLV, that does not require interaction with CD4 or any chemokine receptor to enter into cells. 43,44 Because we produced pseudotyped NL4-3 viruses by transfecting HeLa cells, we first explored the effect in our model of native NL4-3 viruses collected from transfected HeLa cells.…”

Section: X4-tropic Hiv1 Strains Induce Death Of Unstimulated Primary mentioning

confidence: 99%

“…Thus, while the expression by NL4-3 of a retroviral Env protein was required for NL4-3 to induce CD4 þ T-cell killing in the presence of cellular factors released by dying neighboring cells, there was no specific requirement for the expression by NL4-3 of an HIV1 Env protein. Because the MuLV Env uses a high-affinity Na þ -dependent phosphate transporter as a receptor for entry into cells, 43,44 these findings indicated that NL4-3 Envmediated CD4 and CXCR4 signaling were not required to cause CD4 þ T-cell death. Rather, CD4 þ T-cell death was a consequence of either a gp41-independent HIV1 fusion process with the cells or the entry of the HIV1 viral particles into the cells.…”

Section: X4-tropic Hiv1 Nl4-3 Requires Cellular Cofactors Released Bymentioning

confidence: 99%

See 2 more Smart Citations

A novel mechanism for HIV1-mediated bystander CD4+ T-cell death: neighboring dying cells drive the capacity of HIV1 to kill noncycling primary CD4+ T cells

et al. 2004

View full text Add to dashboard Cite

CD4 þ T-cell death is a crucial feature of AIDS pathogenesis, but the mechanisms involved remain unclear. Here, we present in vitro findings that identify a novel process of HIV1 mediated killing of bystander CD4 þ T cells, which does not require productive infection of these cells but depends on the presence of neighboring dying cells. X4-tropic HIV1 strains, which use CD4 and CXCR4 as receptors for cell entry, caused death of unstimulated noncycling primary CD4 þ T cells only if the viruses were produced by dying, productively infected T cells, but not by living, chronically infected T cells or by living HIV1-transfected HeLa cells. Inducing cell death in HIV1-transfected HeLa cells was sufficient to obtain viruses that caused CD4 þ T-cell death. The addition of supernatants from dying control cells, including primary T cells, allowed viruses produced by living HIV1-transfected cells to cause CD4 þ Tcell death. CD4 þ T-cell killing required HIV1 fusion and/or entry into these cells, but neither HIV1 envelope-mediated CD4 or CXCR4 signaling nor the presence of the HIV1 Nef protein in the viral particles. Supernatants from dying control cells contained CD95 ligand (CD95L), and antibody-mediated neutralization of CD95L prevented these supernatants from complementing HIV1 in inducing CD4 þ T-cell death. Our in vitro findings suggest that the very extent of cell death induced in vivo during HIV1 infection by either virus cytopathic effects or immune activation may by itself provide an amplification loop in AIDS pathogenesis. More generally, they provide a paradigm for pathogen-mediated killing processes in which the extent of cell death occurring in the microenvironment might drive the capacity of the pathogen to induce further cell death.

show abstract

Section: Discussionmentioning

confidence: 73%

Section: X4-tropic Hiv1 Strains Induce Death Of Unstimulated Primary mentioning

confidence: 99%

Section: X4-tropic Hiv1 Nl4-3 Requires Cellular Cofactors Released Bymentioning

confidence: 99%

See 1 more Smart Citation

A novel mechanism for HIV1-mediated bystander CD4+ T-cell death: neighboring dying cells drive the capacity of HIV1 to kill noncycling primary CD4+ T cells

et al. 2004

View full text Add to dashboard Cite

show abstract

“…RD envelope protein shares the common cell-surface receptor as HERV-W, 19,20 while GALV enter cells after binding with type-III sodium-dependent phosphate transporters PiT-1. [21][22][23] It has been demonstrated that in D-and C-type mammalian retroviruses, the 16 C-terminal residues of the intracytoplasmic tail of these viruses' envelope proteins, called the 'R-peptide', inhibit their fusion activities. 24,25 Thus R-less versions of these envelope proteins were used in this study, except for the HERV-W, which does not rely on the cleavage of the R-like peptide for its fusing activity.…”

Section: Introductionmentioning

confidence: 99%

Fusogenic membrane glycoproteins induce syncytia formation and death in vitro and in vivo: a potential therapy agent for lung cancer

et al. 2009

View full text Add to dashboard Cite

Fusogenic membrane glycoproteins (FMGs) are viral envelope proteins, which bind surface receptors and induce fusion of the cell membrane. An FMG-transfected cell will fuse with neighbor cells, thus forming syncytia that die within 5 days. In this report, plasmids encoding for FMGs from Human Endogenous Retrovirus-W (HERV-W) was compared with Gibbon Ape Leukemia Virus (GALV) and feline endogenous virus RD-114 (RD). These plasmids were transfected in human non-small-cell lung cancer (NSCLC) cells in vitro or directly injected into tumors in mice. All FMGs induced the formation of syncytia containing around 50 cells. HERV-W or GALV FMGs decreased up to 80% of cell viability in vitro and inhibited tumor growth in vivo (60-70% reduction). In contrast, RD FMG was not efficient. Apoptosis played a role in the death of the syncytia, but addition of the caspase inhibitor Z-VAD-fmk had no effect, suggesting that apoptosis is not the only mechanism responsible for FMG-induced cell death. Altogether, our results demonstrate that even at very low transfection efficiency, the antitumor activity of HERV-W FMG is as effective as that of GALV in vitro and in vivo for the treatment of human lung tumors.

show abstract

“…During viral infection, viruses bind to target cells through specific receptors. 85,86 After entry of the virus, reverse transcriptase transcribes viral RNA into doublestranded DNA that randomly integrates into the genome of the eukaryotic target cell. The new genetic information remains stable in the host cell and will be transmitted to its progeny during mitosis.…”

Section: Retroviral Vectorsmentioning

confidence: 99%

β-Galactosidase marker genes to tag and track human hematopoietic cells

1999

View full text Add to dashboard Cite

A human amphotropic retrovirus receptor is a second member of the gibbon ape leukemia virus receptor family.

Cited by 249 publications

References 37 publications

A novel mechanism for HIV1-mediated bystander CD4+ T-cell death: neighboring dying cells drive the capacity of HIV1 to kill noncycling primary CD4+ T cells

A novel mechanism for HIV1-mediated bystander CD4+ T-cell death: neighboring dying cells drive the capacity of HIV1 to kill noncycling primary CD4+ T cells

Fusogenic membrane glycoproteins induce syncytia formation and death in vitro and in vivo: a potential therapy agent for lung cancer

β-Galactosidase marker genes to tag and track human hematopoietic cells

Contact Info

Product

Resources

About