Efficient replication of human immunodeficiency virus type 1 and measles virus in a human-to-mouse graft versus host disease model permits immunization research.

Abstract

An acute graft versus host disease (GvHD) murine model was developed to study the pathogenic and protective mechanisms against viruses that replicate in cells of the human immune system. The model allowed efficient replication of lymphotropic, macrophage and amphitropic strains of human immunodeficiency virus type 1 (HIV-1) and measles virus (MV). Cytopathic lymphotropic strains of HIV-1 and a wild-type MV strain replicated in a 'burst'-like manner, whereas a non-cytopathic lymphotropic HIV-1 strain and all macrophage-tropic HIV-1 strains caused persistent infection of the graft. The replication kinetics of infection with these viruses were highly reproducible and were very similar to those observed in natural infection of humans. Infection with these viruses, with the exception of HIV-1SF2, led to a delay [corrected] and abrogation of the GvHD, indicating a direct immunosuppressive effect. Interestingly, infection with the lymphotropic HIV-1SF2 strain was rapidly and spontaneously abrogated. The model was also shown to be suitable for the evaluation of passive immunization strategies. Administration of a combination of antibodies against the HIV-1 V3 loop and the HIV-1 CD4 binding sites prevented subsequent infection with HIV-1IIIB. In contrast, administration of CD4 binding site specific human monoclonal antibody at a concentration that would neutralize the virus in vitro enhanced in vivo infection with HIV-1IIIB. The model also allowed evaluation of in vivo immunization studies. Immunization with a live attenuated measles vaccine resulted in protection from a wild-type MV challenge, whereas immunization with a subunit candidate vaccine appeared to give partial protection.