PMID- 22018238 OWN - NLM STAT- MEDLINE DCOM- 20120208 LR - 20230603 IS - 1934-6069 (Electronic) IS - 1931-3128 (Print) IS - 1931-3128 (Linking) VI - 10 IP - 4 DP - 2011 Oct 20 TI - Topical tenofovir, a microbicide effective against HIV, inhibits herpes simplex virus-2 replication. PG - 379-89 LID - 10.1016/j.chom.2011.08.015 [doi] AB - The HIV reverse-transcriptase inhibitor, tenofovir, was recently formulated into a vaginal gel for use as a microbicide. In human trials, a 1% tenofovir gel inhibited HIV sexual transmission by 39% and, surprisingly, herpes simplex virus-2 (HSV-2) transmission by 51%. We demonstrate that the concentration achieved intravaginally with a 1% tenofovir topical gel has direct antiherpetic activity. Tenofovir inhibits the replication of HSV clinical isolates in human embryonic fibroblasts, keratinocytes, and organotypic epithelial 3D rafts, decreases HSV replication in human lymphoid and cervicovaginal tissues ex vivo, and delays HSV-induced lesions and death in topically treated HSV-infected mice. The active tenofovir metabolite inhibits HSV DNA-polymerase and HIV reverse-transcriptase. To exert dual antiviral effects, tenofovir requires topical administration to achieve a drug concentration higher than systemic levels achieved by oral treatment. These findings indicate that a single topical treatment, like tenofovir, can inhibit the transmission of HIV and its copathogens. CI - Copyright (c) 2011 Elsevier Inc. All rights reserved. FAU - Andrei, Graciela AU - Andrei G AD - Rega Institute for Medical Research, K.U. Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium. FAU - Lisco, Andrea AU - Lisco A FAU - Vanpouille, Christophe AU - Vanpouille C FAU - Introini, Andrea AU - Introini A FAU - Balestra, Emanuela AU - Balestra E FAU - van den Oord, Joost AU - van den Oord J FAU - Cihlar, Tomas AU - Cihlar T FAU - Perno, Carlo-Federico AU - Perno CF FAU - Snoeck, Robert AU - Snoeck R FAU - Margolis, Leonid AU - Margolis L FAU - Balzarini, Jan AU - Balzarini J LA - eng SI - GENBANK/JN415116 SI - GENBANK/JN415117 SI - GENBANK/JN415118 SI - GENBANK/JN415119 SI - GENBANK/JN415120 SI - GENBANK/JN415121 SI - GENBANK/JN415122 SI - GENBANK/JN415123 SI - GENBANK/JN415124 SI - GENBANK/JN415125 SI - GENBANK/JN415126 GR - Z01 HD001416-15/ImNIH/Intramural NIH HHS/United States GR - ZIA HD001416/ImNIH/Intramural NIH HHS/United States GR - ZIA HD001416-19/ImNIH/Intramural NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Intramural PL - United States TA - Cell Host Microbe JT - Cell host & microbe JID - 101302316 RN - 0 (Anti-Infective Agents) RN - 0 (DNA, Viral) RN - 0 (Nucleic Acid Synthesis Inhibitors) RN - 0 (Organophosphonates) RN - 0 (Viral Proteins) RN - 99YXE507IL (Tenofovir) RN - EC 2.7.1.21 (Thymidine Kinase) RN - EC 2.7.7.49 (HIV Reverse Transcriptase) RN - EC 2.7.7.7 (DNA-Directed DNA Polymerase) RN - EC 3.1.- (Exodeoxyribonucleases) RN - EC 3.1.11.- (DNA polymerase, Simplexvirus) RN - JAC85A2161 (Adenine) SB - IM MH - Adenine/administration & dosage/*analogs & derivatives MH - Administration, Topical MH - Animals MH - Anti-Infective Agents/*administration & dosage MH - Cells, Cultured MH - DNA, Viral/chemistry/genetics MH - DNA-Directed DNA Polymerase MH - Exodeoxyribonucleases/antagonists & inhibitors MH - HIV Reverse Transcriptase/antagonists & inhibitors MH - Herpes Genitalis/prevention & control/virology MH - Herpesvirus 2, Human/*drug effects MH - Humans MH - Mice MH - Molecular Sequence Data MH - Nucleic Acid Synthesis Inhibitors MH - Organophosphonates/*administration & dosage MH - Sequence Analysis, DNA MH - Tenofovir MH - Thymidine Kinase/genetics MH - Viral Proteins/antagonists & inhibitors/genetics PMC - PMC3201796 MID - NIHMS328183 EDAT- 2011/10/25 06:00 MHDA- 2012/02/09 06:00 PMCR- 2012/10/20 CRDT- 2011/10/25 06:00 PHST- 2011/03/25 00:00 [received] PHST- 2011/06/23 00:00 [revised] PHST- 2011/08/25 00:00 [accepted] PHST- 2011/10/25 06:00 [entrez] PHST- 2011/10/25 06:00 [pubmed] PHST- 2012/02/09 06:00 [medline] PHST- 2012/10/20 00:00 [pmc-release] AID - S1931-3128(11)00289-7 [pii] AID - 10.1016/j.chom.2011.08.015 [doi] PST - ppublish SO - Cell Host Microbe. 2011 Oct 20;10(4):379-89. doi: 10.1016/j.chom.2011.08.015.