9-(2-PHOSPHONYLMETHOXYETHYL)ADENINE INCREASES THE SURVIVAL OF INFLUENZA VIRUS-INFECTED MICE BY AN ENHANCEMENT OF THE IMMUNE-SYSTEM

PMEA (9-(2-phosphonylmethoxyethyl)adenine) is a potent inhibitor of DN A viruses and retroviruses able to enhance natural immune functions su ch as natural killer cell activity and interferon production. The resu lts reported in this paper show that the treatment with PMEA significa tively decreased the mortality of mice challenged with influenza A/PR8 virus (an RNA virus, non sensitive to the antiviral effect of PMEA) c ompared to untreated, infected controls (median survival 8.64 days and 7.61 days, respectively), and reduced lung weight and consolidation ( two surrogate markers of virus infection). Furthermore, virus titer ob tained from lung homogenates was substantially decreased in PMEA-treat ed mice compared to controls. Finally, enhancement of natural killer c ell activity was achieved in PMEA-treated A/PR8-infected mice compared to A/PR8-infected controls. Overall, results suggest that PMEA decrea ses the influenza virus-related mortality and morbidity through the en hancement of some immune functions, and that this effect might be addi tive or even synergystic with the direct inhibitory effect of DNA viru ses or retroviruses induced by PMEA itself. This supports the importan ce of evaluating this drug in patients with diseases related to herpes viruses or to human immunodeficiency virus.