title: Inhibition of pathogenic SHIV replication in macaques treated with antisense DNA of interleukin-4.
abstract: Interleukin-4 is implicated in the pathogenesis of HIV-induced AIDS and causes enhancement of replication of virus strains that use the CXCR4 (X4) coreceptor. In this study, we explored the effects of interleukin-4 (IL-4) antisense (AS) DNA on replication of X4, simian human immunodeficiency viruses, SHIV(KU-2) and SHIV89.6P. AS IL-4 oligomer caused inhibition of virus replication in cultures of CD4+ T cells and macrophages derived from macaques. Plasmid expressing AS IL-4 DNA was also effective in abrogating virus replication in macrophage cultures. Relevance of these cell culture studies was confirmed in vivo by treating SHIV89.6P-infected macaques with AS IL-4 DNA. Six macaques were inoculated with the virus, and 4 were treated with AS IL-4 DNA. This resulted in a significant decrease in viral RNA concentrations in the liver, lungs, and spleen tissues that are all sites of virus replication in macrophages. This is the first demonstration of effective inhibition of an HIV-like virus in tissues by AS DNA of a cytokine. In the present era of increasing resistance of HIV to antiviral compounds, exploration of adjunct therapies directed at host responses in combination with antiretroviral drugs may be of value for the treatment of AIDS.
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics, University of Kansas Medical Center, Kansas City, KS 66160, USA.
authors.forename: Navneet Kaur
authors.initials: NK
authors.lastname: Dhillon
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Sui
authors.forename: Raghava
authors.initials: R
authors.lastname: Potula
authors.forename: Sukhbir
authors.initials: S
authors.lastname: Dhillon
authors.forename: Istvan
authors.initials: I
authors.lastname: Adany
authors.forename: Zhuang
authors.initials: Z
authors.lastname: Li
authors.forename: Francois
authors.initials: F
authors.lastname: Villinger
authors.forename: David
authors.initials: D
authors.lastname: Pinson
authors.forename: Opendra
authors.initials: O
authors.lastname: Narayan
authors.forename: Shilpa
authors.initials: S
authors.lastname: Buch
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000821:virology; D002478:Cells, Cultured; D016373:DNA, Antisense / Q000494:pharmacology*; D015316:Genetic Therapy / Q000379:methods*; D049452:Green Fluorescent Proteins / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics*; D008081:Liposomes; D008251:Macaca; D008264:Macrophages / Q000166:cytology / Q000821:virology; D010957:Plasmids / Q000494:pharmacology; D019718:Receptors, CXCR4 / Q000235:genetics; D016097:Simian Acquired Immunodeficiency Syndrome / Q000628:therapy* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000254:growth & development*; D014779:Virus Replication
chemical_list: D016373:DNA, Antisense; D008081:Liposomes; D019718:Receptors, CXCR4; D049452:Green Fluorescent Proteins; D015847:Interleukin-4