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Alkoxyalkyl Esters Of 9-(S)-(3-Hydroxy-2-Phosphonomethoxypropyl) Adenine Are Potent And Selective Inhibitors Of Hepatitis B Virus (Hbv) Replication In Vitro And In Hbv Transgenic Mice In Vivo, John D. Morrey, B E. Korba, J R. Beadle, D L. Wyles, K Y. Hostetler
Alkoxyalkyl Esters Of 9-(S)-(3-Hydroxy-2-Phosphonomethoxypropyl) Adenine Are Potent And Selective Inhibitors Of Hepatitis B Virus (Hbv) Replication In Vitro And In Hbv Transgenic Mice In Vivo, John D. Morrey, B E. Korba, J R. Beadle, D L. Wyles, K Y. Hostetler
John D. Morrey
Alkoxyalkyl esters of acyclic nucleoside phosphonates have previously been shown to have increased antiviral activity when they are administered orally in animal models of viral diseases, including lethal infections with vaccinia virus, cowpox virus, ectromelia virus, murine cytomegalovirus, and adenovirus. 9-(S)-(3-Hydroxy-2-phosphonomethoxypropyl)adenine [(S)-HPMPA] was previously shown to have activity against hepatitis B virus (HBV) in vitro. To assess the effect of alkoxyalkyl esterification of (S)-HPMPA, we prepared the hexadecyloxypropyl (HDP), 15-methyl-hexadecyloxypropyl (15M-HDP), and octadecyloxyethyl (ODE) esters and compared their activities with the activity of adefovir dipivoxil in vitro and in vivo. Alkoxyalkyl esters of (S)-HPMPA were 6 to 20 times more …
In Vivo Activation Of Human Immunodeficiency Virus Type 1 Long Terminal Repeat By Uv Type A (Uv-A) Light Plus Psoralen And Uv-B Light In The Skin Of Transgenic Mice, John D. Morrey, S M. Bourn, T D. Bunch, M K. Jackson, R W. Sidwell, L R. Barrows, R A. Daynes, C A. Rosen
In Vivo Activation Of Human Immunodeficiency Virus Type 1 Long Terminal Repeat By Uv Type A (Uv-A) Light Plus Psoralen And Uv-B Light In The Skin Of Transgenic Mice, John D. Morrey, S M. Bourn, T D. Bunch, M K. Jackson, R W. Sidwell, L R. Barrows, R A. Daynes, C A. Rosen
John D. Morrey
UV irradiation has been shown to activate the human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) in cell culture; however, only limited studies have been described in vivo. UV light has been categorized as UV-A (400 to 315 nm), -B (315 to 280 nm), or -C (<280 nm); the longer wavelengths are less harmful but more penetrative. Highly penetrative UV-A radiation constitutes the vast majority of UV sunlight reaching the earth's surface but is normally harmless. UV-B irradiation is more harmful but less prevalent than UV-A. In this report, the HIV-1 LTR-luciferase gene in the skin of transgenic mice was markedly activated when exposed to UV-B irradiation. The LTR in the skin of transgenic mice pretreated topically with a photosensitizing agent (psoralen) was also activated to similar levels when exposed to UV-A light. A 2-h exposure to sunlight activated the LTR in skin treated with psoralen, whereas the LTR in skin not treated with psoralen was activated after 7 h of sunlight exposure. The HIV-1 LTR-β-galactosidase reporter genes have been used to demonstrate the in vivo UV-induced activation of the LTR and might be used to evaluate other environmental factors or pharmacologic substances that might potential activate the HIV-1 LTR in vivo