Protective effect of MDP-Lys(L18), a synthetic derivative of muramyldipeptide, on murine cytomegalovirus infection.
The host-mediated antiviral effect of N alpha-(N-acetylmuramyl-L-alanyl-D-isoglutaminyl)-N epsilon-stearoyl-L-lysine [MDP-Lys(L18)] was evaluated in mice against murine cytomegalovirus (MCMV) infection. Mice treated with 800 micrograms of MDP-Lys(L18) on day 2 before the virus challenge survived systemic lethal infection. The protective effect of MDP-Lys(L18) was evidenced by an increase in plaque-forming units per LD50 and a decrease in virus titers in the target organs. No significant difference in the serum interferon level and 2',5'-oligoadenylate synthetase activity was observed among the mice treated with test compounds or phosphate-buffered saline, thought they were higher in MCMV-infected mice than in mock-infected mice. The natural killer (NK) activity was augmented remarkably in the mice treated with MDP-Lys(L18) or its original component, muramyldipeptide (MDP). MDP-Lys(L18) showed neither virocidal nor virostatic activity on MCMV in vitro. Thus, MDP-Lys(L18)-induced resistance against MCMV infection seems to be host-mediated. The MDP-Lys(L18)-induced resistance was not abrogated by the treatment with anti-asialo GM1 serum. The NK activity augmented by MDP-Lys(L18) may contribute to some part of the protective effect, though the augmentation of the NK activity alone did not correlate completely with the protective effect of MDP-Lys(L18). In addition, no difference was observed in anti-MCMV activity among peritoneal exudate cells from mice treated with MDP-Lys(L18), MDP or phosphate-buffered saline. Therefore, another host-mediated factor(s) may also participate in the antiviral effect of MDP-Lys(L18).
Eizuru
Y
Y
Department of Microbiology, Miyazaki Medical College, Japan.
Nakagawa
N
N
Hamasuna
R
R
Minamishima
Y
Y
D015088:2',5'-Oligoadenylate Synthetase / Q000187:drug effects; D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D003587:Cytomegalovirus / Q000187:drug effects; D003586:Cytomegalovirus Infections / Q000276:immunology / Q000517:prevention & control*; D005260:Female; D005677:G(M1) Ganglioside / Q000276:immunology; D007372:Interferons / Q000187:drug effects; D007694:Killer Cells, Natural / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D014779:Virus Replication / Q000187:drug effects
D000276:Adjuvants, Immunologic; D005677:G(M1) Ganglioside; D000119:Acetylmuramyl-Alanyl-Isoglutamine; C018835:asialo GM1 ganglioside; D007372:Interferons; D015088:2',5'-Oligoadenylate Synthetase; C036866:romurtide