Protective activity of lipid A analogue GLA-60 against murine cytomegalovirus infection in mice

✍ Scribed by Dr. Satoru Ikeda; Johan Neyts; Motohiro Matsuura; Makoto Kiso; Akira Hasegawa; Chiaki Nishimura; Erik De Clercq

• Publisher: John Wiley and Sons
• Year: 1993
• Tongue: English
• Weight: 571 KB
• Volume: 40
• Category: Article
• ISSN: 0146-6615
• DOI: 10.1002/jmv.1890400310

✦ Synopsis

Abstract

A chemically synthesized lipid A subunit analogue, GLA‐60 (2‐deoxy‐4–0‐phosphono‐2‐[(3R)‐3‐hydroxytetradecanamido] ‐ 3 ‐ 0‐ [(3R) ‐ 3 ‐tetradecanoyloxytetradecanoyl]‐D‐glucose), has many of the activities of endotoxins but little, if any, toxicity. We investigated the protective activity of GLA‐60 against murine cytomegalovirus (MCMV) infection in NMRI mice. Intraperitoneal administration of GLA‐60 at 1 day before MCMV infection at doses of 1, 10, or 100 μg per mouse significantly reduced mortality. GLA‐60 stimulated peritoneal natural killer (NK) cell and macrophage activities, and these activities were abolished by in vitro treatment with anti‐asialo GM~1~ antibody and anti‐Mac~1~ antibody, respectively. GLA‐60 proved also protective against MCMV infection in mice in which either NK cells or macrophages were depleted by in vivo treatment with anti‐asialo GM~1~ or anti‐Mac~1~ antibody. The anti‐MCMV activity of GLA‐60 can at least be partially attributed to activation of NK cells and macrophages. © 1993 Wiley‐Liss, Inc.