Opportunistic infections in mice infected with LP-BM5 murine retrovirus on a binge ethanol diet.

Abstract

A murine model of AIDS (Acquired Immune Deficiency Syndrome) for study of immunomodulatory effects of alcohol on opportunistic infection was developed. C57BL-6 female mice were infected with murine retrovirus, LP-BM5. Mice were fed a liquid diet containing alcohol which produced withdrawal upon cessation. Controls were fed the diet with sucrose replacing ethanol. Dramatic differences were observed in spleen weight and thymus weight, but not body weight in virus infected or virus infected mice fed the alcohol diet. Ethanol suppressed the numbers of T-cells and macrophages. There was significant changes due to virus infection with and without alcohol treatment in T-subsets, B-cells and macrophages. However none were seen due to ethanol in uninfected controls. Alcohol further suppressed immune functions in retrovirally infected mice beyond that caused by the virus. Some mice were challenged with Streptococcus pneumoniae and Cryptosporodium. Adult mice that had been infected with LP-BM5 virus for 3, 4, or 5 months, when challenged by the oral route with Cryptosporidium, exhibited significant colonization on the intestinal villiae by this organism 10 days following oral challenge. Control mice did not show any oocyst in the villiae after 10 days following oral challenge. Resistance to S. pneumoniae was significantly reduced by retroviral infection, but not by short-term, binge, exposure to dietary ethanol. After 38 days of LP-BM5 infection, the virus infected alcohol fed group showed the shortest survival. The effects of immunization to S. pneumoniae antigens, as well as adoptively transferred cells in virally infected mice were studied. Survival of the mice to S. pneumoniae were influenced by different immunizations. The virus infected group had a much faster death rate in comparison than longer surviving unifected controls. Immunization played an important role in delaying the death rate in all treated groups. Transferring normal spleen cells from healthy, unimmunized mice also enabled the retrovirally infected mice to survive the bacterial infection longer than unimmunized, but retrovirally infected mice. This indicated the potential to enhance resistance by immunization and the transfer of immunocompetent cells to a system, immunosuppressed by retroviral infection. Clearly, retroviral infection modulates resistance with additional effects of ethanol. This model further expands and defines LP-BM5 infection as a murine model of retrovirally induced immune deficiency.