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Immunomodulator effects on the Friend virus infection in genetically defined mice
R W Sidwell1, J D Morrey, K M Okleberry
1Institute for Antiviral Research, Utah State University, Logan 84322-5600.
Abstract:
The disease induced by the Friend virus complex (FV) in F1 hybrid mice containing the Rfv-3r/s genotype in the presence of H-2a/a was used to evaluate a variety of immunomodulating substances. In these genetically defined mice, the FV disease results in splenomegaly, early production of high titers of cell-associated and plasma virus, high levels of splenic viral RNA, increased hematocrit, and eventual death. As the disease progresses, reduced levels of infectious virus correlate with development of specific antibody; reduction in T cell populations, increase in B cells, and decrease in T-cell function also occur. The following immunomodulators were evaluated, listed in the order of their ability to inhibit the FV disease: imexon > MVE-2 > human recombinant IFN-alpha A/D > AS101 > ampligen > AM-3 = oxamisole > ImuVert > bropirimine. In fact, bropirimine, used with certain treatment regimens, appeared to enhance the FV disease. These data suggest that certain immunomodulators may have potential value in the treatment of HIV disease, but also indicate that caution should be exercised in their clinical use.
Insights
Certain immunomodulators show potential for treating Friend virus complex (FV) disease in mice, with imexon being most effective. Caution is advised for clinical use, as some substances may worsen FV disease.
Area of Science:
- Immunology
- Virology
- Pharmacology
Background:
- Friend virus complex (FV) infection in genetically defined F1 hybrid mice (Rfv-3r/s, H-2a/a) causes splenomegaly, high viral loads, and mortality.
- Disease progression involves decreased T-cell function and populations, alongside increased B cells and antibody production.
Purpose of the Study:
- To evaluate the efficacy of various immunomodulating substances in inhibiting FV disease progression.
- To assess the potential of these immunomodulators for treating viral infections, including human immunodeficiency virus (HIV) disease.
Main Methods:
- Utilized a mouse model of FV disease with specific genetic background (Rfv-3r/s, H-2a/a).
- Administered and evaluated a list of immunomodulators: imexon, MVE-2, human recombinant IFN-alpha A/D, AS101, ampligen, AM-3, oxamisole, ImuVert, and bropirimine.
Main Results:
- Immunomodulators were ranked by their ability to inhibit FV disease: imexon > MVE-2 > IFN-alpha A/D > AS101 > ampligen > AM-3 = oxamisole > ImuVert > bropirimine.
- Bropirimine, in some regimens, exacerbated FV disease, highlighting potential adverse effects.
Conclusions:
- Several immunomodulators demonstrate potential therapeutic value against FV infection.
- Findings suggest possible applications for HIV disease treatment, but underscore the need for careful clinical evaluation due to variable efficacy and potential for disease enhancement.