title: Influence of Acyclic Nucleoside Phosphonate Antivirals on Gene Expression of Chemokine Receptors CCR5 and CXCR4.
abstract: Acyclic nucleoside phosphonates (ANPs) are potent antiviral agents effective against replication of DNA viruses and retroviruses including human immunodeficiency virus (HIV). Prototype compound 9-(R)-[2-(phosphonomethoxy)propyl]adenine (tenofovir) is a principal component of drugs widely used in the treatment of HIV infection (Viread, Truvada). Besides their antimetabolic mode of action, ANPs possess immunomodulatory properties. A number of them have been previously found to stimulate secretion of cytokines and anti-HIV effective chemokines. In the present pilot experiments we analysed the in vitro effects of ANPs on the expression of chemokine receptors CCR5 and CXCR4 that are co-receptors of HIV-1 entry in cells. The impact of ANPs was investigated at the level of gene transcription of mRNA in mouse lymphocytes and macrophages using the RT-PCR method. The following compounds were included in the study: 9-(R)-[2-(phosphonomethoxy) propyl]adenine (tenofovir), N6-cyclopropyl-(R)- 9-[2-(phosphonomethoxy)-propyl]2,6-diaminopurine, N6-cyclopentyl-(R)-9-[2-(phosphonomethoxy) propyl]2,6-diaminopurine, N6-dimethylaminoethyl-(R)-9-[2-(phosphonomethoxy)propyl]2,6-diaminopurine, N6-cyclopentyl-9-[2-(phosphonomethoxy) ethyl]2,6-diaminopurine, N6-isobutyl-9-[2-(phosphonomethoxy) ethyl]2,6-diaminopurine. Gene transcription of chemokine receptors CCR5 and CXCR4 was not affected after application of these acyclic nucleoside phosphonate antivirals.
authors.affiliation: Department of Pharmacology, Third Faculty of Medicine, Charles University in Prague, Czech Republic.
authors.forename: P
authors.initials: P
authors.lastname: Potměšil
authors.affiliation: Institute of Organic Chemistry and Biochemistry of Academy of Sciences of the Czech Republic v. v. i., Prague, Czech Republic.
authors.forename: A
authors.initials: A
authors.lastname: Holý
authors.affiliation: Institute of Experimental Medicine of Academy of Sciences of the Czech Republic v. v. i., Prague, Czech Republic.
authors.forename: Z
authors.initials: Z
authors.lastname: Zídek
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D008810:Mice, Inbred C57BL; D009705:Nucleosides / Q000737:chemistry / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019713:Receptors, CCR5 / Q000235:genetics* / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000235:genetics* / Q000378:metabolism
chemical_list: D000998:Antiviral Agents; D009705:Nucleosides; D012333:RNA, Messenger; D019713:Receptors, CCR5; D019718:Receptors, CXCR4