Amphotropic Murine Leukemia Retrovirus Is Not an Acute Pathogen for Primates

The in vivo fate of amphotropic murine leukemia retrovirus was studied in five rhesus monkeys. Retrovirus infused intravenously into 3 normal animals and 1 immunosuppressed animal was cleared rapidly from the circulation and subsequent viremia has not been detected (mean follow-up of 27.4 months). A fifth monkey was immunosuppressed and transplanted with virus-producing autologous fibroblasts in addition to an intraperitoneal injection of virus. This animal was viremic for 2 days and its lymph node cells and peripheral blood mononuclear cells were shown to be producing virus for up to 22 days post-inoculation, but subsequently has been negative after 17.0 months of analysis. In the 5 animals studied (combined mean follow-up of 25.7 months), clinical illness has not been identified at any time. Therefore, murine amphotropic retroviruses do not appear to pose an acute health risk. The major concern of the committees that reviewed the first human gene transfer clinical protocol (which used a murine amphotropic retroviral vector) was safety. One critical issue was whether or not exposure to murine amphotropic retroviruses might be a health risk for the patient and/or for health care personnel. Cornetta et al. present studies done in rhesus monkeys that address this issue. The committees used these studies as part of the evidence they evaluated to determine that the human gene transfer protocol would not present a risk to public health or to the environment.