Protective activity of the lipid A analogue GLA-60 against murine cytomegalovirus infection in immunodeficient mice.
The immunomodulating and murine cytomegalovirus (MCMV)-inhibiting effects of the synthetic lipid A subunit analogue GLA-60 were investigated in different strains of immunodeficient mice. Peritoneal natural killer (NK) cells obtained from nude (nu/nu) C57BL/6 mice or normal NMRI mice, which had been treated intraperitoneally with 10 micrograms of GLA-60 1 day earlier, exhibited a greater cytolytic activity than those from untreated mice. GLA-60 also stimulated NK cell activity in SCID (severe combined immune deficiency) mice (which are T and B cell-defective), but not in NK cell-defective beige (C57BL/6 bg/bg) mice. GLA-60 also enhanced the phagocytic activity of peritoneal macrophages in beige, nude and NMRI mice, but not in SCID mice. GLA-60, when administered as a single 150 micrograms dose 1 day before infection, completely protected beige mice against MCMV-associated mortality. It also caused a significant increase in the life-span of MCMV-infected nude and SCID mice.
Ikeda
S
S
Rega Institute for Medical Research, Leuven, Belgium.
Neyts
J
J
Matsuura
M
M
Kiso
M
M
Hasegawa
A
A
Nishimura
C
C
De Clercq
E
E
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D003587:Cytomegalovirus / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000276:immunology / Q000517:prevention & control*; D007694:Killer Cells, Natural / Q000276:immunology; D008050:Lipid A / Q000031:analogs & derivatives* / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL / Q000276:immunology; D008815:Mice, Inbred Strains / Q000276:immunology; D008819:Mice, Nude / Q000276:immunology*; D016513:Mice, SCID / Q000276:immunology*; D010587:Phagocytosis / Q000187:drug effects; D013045:Species Specificity
D000998:Antiviral Agents; D008050:Lipid A; C056260:GLA 60