DING proteins from phylogenetically different species share high degrees of sequence and structure homology and block transcription of HIV-1 LTR promoter.
Independent research groups reported that DING protein homologues isolated from bacterial, plant and human cells demonstrate the anti-HIV-1 activity. This might indicate that diverse organisms utilize a DING-mediated broad-range protective innate immunity response to pathogen invasion, and that this mechanism is effective also against HIV-1. We performed structural analyses and evaluated the anti-HIV-1 activity for four DING protein homologues isolated from different species. Our data show that bacterial PfluDING, plant p38SJ (pDING), human phosphate binding protein (HPBP) and human extracellular DING from CD4 T cells (X-DING-CD4) share high degrees of structure and sequence homology. According to earlier reports on the anti-HIV-1 activity of pDING and X-DING-CD4, other members of this protein family from bacteria and humans were able to block transcription of HIV-1 and replication of virus in cell based assays. The efficacy studies for DING-mediated HIV-1 LTR and HIV-1 replication blocking activity showed that the LTR transcription inhibitory concentration 50 (IC50) values ranged from 0.052-0.449 ng/ml; and the HIV-1 replication IC50 values ranged from 0.075-0.311 ng/ml. Treatment of cells with DING protein alters the interaction between p65-NF-κB and HIV-1 LTR. Our data suggest that DING proteins may be part of an innate immunity defense against pathogen invasion; the conserved structure and activity makes them appealing candidates for development of a novel therapeutics targeting HIV-1 transcription.
Molecular Virology Division, St. Luke's-Roosevelt Institute for Health Sciences/Columbia University, New York, New York, United States of America.
Rakhee
R
Sachdeva
Nune
N
Darbinian
Kamel
K
Khalili
Shohreh
S
Amini
Daniel
D
Gonzalez
Ahmed
A
Djeghader
Eric
E
Chabriére
Andrew
A
Suh
Ken
K
Scott
Malgorzata
M
Simm
D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D017124:Conserved Sequence; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D006801:Humans; D020902:Hypericum; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D008969:Molecular Sequence Data; D052002:NF-kappa B p50 Subunit / Q000737:chemistry; D010802:Phylogeny; D063150:Polycomb Repressive Complex 1 / Q000737:chemistry / Q000494:pharmacology*; D011401:Promoter Regions, Genetic / Q000187:drug effects* / Q000235:genetics; D055503:Protein Multimerization / Q000187:drug effects; D020836:Protein Structure, Quaternary; D011551:Pseudomonas fluorescens; D017386:Sequence Homology, Amino Acid; D020079:Terminal Repeat Sequences / Q000235:genetics*; D051996:Transcription Factor RelA / Q000737:chemistry; D014158:Transcription, Genetic / Q000187:drug effects*; D014779:Virus Replication / Q000187:drug effects
D019380:Anti-HIV Agents; D052002:NF-kappa B p50 Subunit; D051996:Transcription Factor RelA; D063150:Polycomb Repressive Complex 1; C489841:RNF2 protein, human