TROJAN HORSE MACROPHAGES - STUDIES WITH THE MURINE LACTATE DEHYDROGENASE-ELEVATING VIRUS AND IMPLICATIONS FOR SEXUALLY-TRANSMITTED VIRUS-INFECTION

Previous studies have suggested that monocytes or macrophages may medi ate internal virus spread. For the present study, the tissue distribut ion and infectious potential of dye-labelled and/or lactate dehydrogen ase-elevating virus (LDV)-infected murine macrophages were determined. Murine peritoneal macrophages were labelled with the fluorescent carb ocyanine tracking dye DiI, injected into mice, and the tissue distribu tion of DiI-labelled cells was determined by fluorescence analysis of frozen sections. Mice receiving intravenous (i.v.) or intraperitoneal injections of DiI-labelled macrophages displayed rapid and broad tissu e distribution of the labelled cells. Intravaginal injection of DiI-la belled macrophages resulted in penetration into the placentas, but not the fetuses, of pregnant mice. When macrophages were LDV-infected and DiI-labelled prior to i.v. injection into pregnant mice, they homed t o various tissues including the placenta, but were not found in fetuse s. Intravaginal injection of LDV-infected macrophages resulted in syst emic LDV infection, even though the free-virus dose was less than the minimum infectious dose by this route. Neither polyclonal nor monoclon al IgG anti-LDV antibodies protected mice from vaginal infection with cell-associated virus, and LDV-immune complexes were themselves infect ious by the vaginal route. These results show that exogenous macrophag es are widely distributed following parenteral injection, penetrate lo cally to placentas after intravaginal injection, and are capable of ac ting vaginally as relatively efficient virus infection-delivery vehicl es. Thus, 'Trojan Horse' macrophages are potentially infectious vehicl es both for internal virus spread and for animal-to-animal transmissio n.