Identification of X-DING-CD4, a new member of human DING protein family that is secreted by HIV-1 resistant CD4(+) T cells and has anti-viral activity.
We reported previously the anti-viral activity named HRF (HIV-1 Resistance Factor) secreted by HIV-1 resistant cells. This work describes the identification of HRF from cell culture supernatant of HRF-producing cells (HRF(+) cells). Employing the proteomics and cell based activity assay we recovered ten peptides sharing 80-93% sequence homology with other eukaryotic DING proteins; discrete amino acid characteristics found in our material suggested that HRF is a new member of DING proteins family and consequently we designated it as X-DING-CD4 (extracellular DING from CD4(+) T cells). The presence of X-DING-CD4 in the extracellular compartment of HRF(+) but not control HRF(-) cells was confirmed by specific anti-X-DING-CD4 antibody. Similar as the un-fractionated HRF(+) cell culture supernatant, the purified X-DING-CD4 blocked transcription of HIV-1 LTR-promoted expression of luciferase gene and replication of HIV-1 in MAGI cells. The X-DING-CD4 -mediated anti-viral activity in MAGI cells could be blocked by specific antibody.
Lesner
Adam
A
Protein Chemistry Laboratory, St. Luke's/Roosevelt Institute for Health Sciences, Columbia University, New York, NY 10019, USA.
Shilpi
Rasheda
R
Ivanova
Anna
A
Gawinowicz
Mary Ann
MA
Lesniak
Jacob
J
Nikolov
Dimitar
D
Simm
Malgorzata
M
D000595:Amino Acid Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008969:Molecular Sequence Data; D063150:Polycomb Repressive Complex 1; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C544193:X-DING-CD4 protein, human; D063150:Polycomb Repressive Complex 1; C489841:RNF2 protein, human; D044767:Ubiquitin-Protein Ligases