Elucidation of mode of retroviral-inhibitory effects of imexon through use of immune competent and severe combined immune deficiency (SCID) mice.
Mice infected with various tumor retroviruses have been used as models for evaluating therapeutic substances for the treatment of some cancers, and more recently, for human immunodeficiency virus (HIV) infection, the causative agent of acquired immune deficiency syndrome (AIDS). Consequently, there is a need to determine the ability of biological response modifiers (BRMs) to specifically reduce virus-infected cells, as compared to their non-specific anti-proliferative effects. To address this need, a BRM, imexon, was evaluated in this study using three strains of mice having different Friend virus (FV)-specific immunological capabilities. The first strain, (B10.A x A/WySn)F1, was genetically capable of producing FV-specific neutralization and cytotoxic antibodies, the second, Balb/c, was not, and the third, SCID mice, lacked functional T and B cell immunity. Imexon treatment reduced virally-induced splenomegaly in all 3 strains; however, the concentration of splenic viral infectious centers (IC) were not affected. Since imexon was efficacious in reducing splenomegaly in SCID mice, the mode of action was concluded to not require functional T or B cell immunity. The observation that imexon did not affect splenic IC titers also suggested that imexon did not specifically eliminate virally infected cells, but may have functioned by other mechanisms. This study also demonstrated the use of various mouse strains as a strategy for delineating the modes of action of BRMs against murine retroviral infections.
Morrey
J D
JD
AIDS Research Program, Utah State University, Logan 84322-5600.
Mead
J R
JR
Warren
R P
RP
Okleberry
K M
KM
Burger
R A
RA
Sidwell
R W
RW
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D001402:B-Lymphocytes / Q000276:immunology; D004198:Disease Susceptibility; D005260:Female; D005622:Friend murine leukemia virus / Q000187:drug effects* / Q000276:immunology; D006588:Hexanones / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D012192:Retroviridae Infections / Q000188:drug therapy* / Q000276:immunology; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology
D000998:Antiviral Agents; D006588:Hexanones; C014919:4-imino-1,3-diazabicyclo(3.1.0)hexan-2-one