Measurement of Viral Infection in the Early Stages of Friend Disease

Abstract

The study of the Friend virus complex has provided important insights into cancer and other retroviral diseases. This mixture of retroviruses commences disease almost immediately after inoculation, and the indications may include: splenomegaly, unrestrained proliferation of the reticulum cells, progressive lymphocytosis, hepatomegaly, and erythroblastosis. While Friend disease is well studied, the dynamics of virus replication during the early stages of Friend disease are unknown. Polymerase Chain Reaction (PCR) was used to monitor the kinetics of viral spread by two components of the Friend virus complex. The number of proviruses present in DNA, from the blood and spleen cells of mice infected with the Friend viral complex, was determined. The spread of replication-competent Friend murine leukemia virus (F-MuLV) was found to precede the replication-defective spleen focus-forming virus (SFFVp). Additionally, the detection of Friend viral DNA was first found in the peripheral blood. It was not until later in the course of the disease that the provirus was detected in the spleen. The PCR detection technique allowed for the development of an animal model to monitor the effects of anti-viral compounds in vivo. This system showed that one zinc-finger oxidizing compound, AldrithioI-2, was capable of suppressing viral replication greater than two orders of magnitude, as measured in a six day assay. This study has established a method to detect the presence of Friend provirus, to quantitate the amount of proviral DNA which can project the rise in viral replication, and to directly detect viral replication when zinc-finger oxidizing compounds are administered to an in vivo system.