title: Cellular resistance to HIV-1 infection in target cells coincides with a rapid induction of X-DING-CD4 mRNA: indication of the unique host innate response to virus regulated through function of the X-DING-CD4 gene.
abstract: Clinical reports indicate that some infected individuals control HIV-1 replication through undefined mechanisms. Our group reported that a human protein named X-DING-CD4 holds a potent antiviral activity, blocking transcription of HIV-1 LTR through the inhibition of NF-κB/DNA binding. Based on observations that transformed HIV-1 resistant CD4(+) T cells produce higher levels of soluble X-DING-CD4 protein upon their exposure to virus, we hypothesized that resistance to HIV-1 in these cells may be regulated through function of the X-DING-CD4 gene. Real-time PCR evaluations of X-DING-CD4 mRNA expression confirmed our hypothesis; HIV-1 exposure caused rapid up-regulation of X-DING-CD4 mRNA in resistant, but not susceptible, cells; and the burst of X-DING-CD4 mRNA expression correlated with restriction of HIV-1 transcription. Subsequently, we examined the activity of the X-DING-CD4 gene in monocytes and macrophages from (n = 13) HIV-negative donors. The assessment of HIV-1 gag mRNA showed that the majority of cells were permissive to virus replication; however, macrophages from four donors were refractory to HIV-1 infection. In response to virus, these cells up-regulated X-DING-CD4 gene expression by 2- to 1000-fold. These data provide evidence that the X-DING-CD4 gene contributes to early cellular protection from HIV infection in some individuals and this protection depends solely on the unique genetic regulation of the host.
authors: Protein Chemistry Laboratory, St. Luke's/Roosevelt Institute for Health Sciences, Columbia University, New York, USA.
authors: Rasheda Y
authors: RY
authors: Shilpi
authors: Rakhee
authors: R
authors: Sachdeva
authors: Malgorzata
authors: M
authors: Simm
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D002352:Carrier Proteins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral; D015967:Gene Expression Regulation, Viral; D015658:HIV Infections / Q000235:genetics* / Q000276:immunology; D015497:HIV-1 / Q000502:physiology*; D054884:Host-Pathogen Interactions / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D008264:Macrophages / Q000276:immunology / Q000821:virology*; D009000:Monocytes / Q000276:immunology* / Q000821:virology; D016328:NF-kappa B / Q000378:metabolism; D011485:Protein Binding; D012333:RNA, Messenger / Q000032:analysis; D014779:Virus Replication
chemical_list: D002352:Carrier Proteins; D016328:NF-kappa B; D012333:RNA, Messenger; C544193:X-DING-CD4 protein, human