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.