Protective activity of lipid A analogue GLA-60 against murine cytomegalovirus infection in mice.
A chemically synthesized lipid A subunit analogue, GLA-60 (2-deoxy-4-O-phosphono-2-[(3R)-3-hydroxytetradecanamido]-3-O-[(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 micrograms 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 GM1 antibody and anti-Mac1 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 GM1 or anti-Mac1 antibody. The anti-MCMV activity of GLA-60 can at least be partially attributed to activation of NK cells and macrophages.
Rega Institute for Medical Research, Leuven, Belgium.
S
S
Ikeda
J
J
Neyts
M
M
Matsuura
M
M
Kiso
A
A
Hasegawa
C
C
Nishimura
E
E
De Clercq
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D003586:Cytomegalovirus Infections / Q000517:prevention & control*; D005260:Female; D005677:G(M1) Ganglioside / Q000037:antagonists & inhibitors; D007274:Injections, Intraperitoneal; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D008050:Lipid A / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects; D016177:Macrophage-1 Antigen; D051379:Mice; D010587:Phagocytosis / Q000187:drug effects
D000276:Adjuvants, Immunologic; D008050:Lipid A; D016177:Macrophage-1 Antigen; C056260:GLA 60; D005677:G(M1) Ganglioside; C018835:asialo GM1 ganglioside