Antiviral efficacy of nine nucleoside reverse transcriptase inhibitors against feline immunodeficiency virus in feline peripheral blood mononuclear cells

作者：Schwartz Anita M; McCrackin Mary Ann; Schinazi Raymond F; Hill Peter B; Vahlenkamp Thomas W; Tompkins Mary B; Hartmann Katrin^*

来源：American Journal of Veterinary Research, 2014, 75(3): 273-281.

Objective-To compare cytotoxic effects and antiviral efficacy of 9 nucleoside reverse transcriptase inhibitors (NRTIs) against FIV in feline peripheral blood mononuclear cells.
Sample-Peripheral blood mononuclear cells obtained from 3 specific pathogen-free cats.
Procedures-3 of the 9 NRTIs had not been previously assessed in feline cell lines. Cytotoxic effects were determined by colorimetric quantification of a formazan product resulting from bioreduction of a tetrazolium reagent by viable peripheral blood mononuclear cells; uninfected cells from 1 cat were used in these assays. Cells from all 3 cats were infected with a pathogenic clone of FIV, and in vitro antiviral efficacy of each NRTI was assessed with an FIV p24 antigen capture ELISA.
Results-Cytotoxic effects in feline peripheral blood mononuclear cells were observed only at concentrations > 10 mu M for all 9 NRTIs. Comparison of the cytotoxic effect at the highest concentration investigated (500 mu M) revealed that didanosine and amdoxovir were significantly less toxic than abacavir. All drugs induced a dose-dependent reduction of FIV replication. At the highest concentration investigated (10 mu M), there was no significant difference in antiviral efficacy among the test compounds.
Conclusions and Clinical Relevance-The evaluated NRTIs had low cytotoxicity against feline peripheral blood mononuclear cells and appeared to be safe options for further in vivo evaluation for the treatment of FIV-infected cats. There was no evidence suggesting that the newly evaluated compounds would be superior to the existing NRTIs for reducing FIV burden of infected cats.

• 出版日期2014-3