THE MA (P15) AND P12 REGIONS OF THE GAG GENE ARE SUFFICIENT FOR THE PATHOGENICITY OF THE MURINE AIDS VIRUS

Inoculation of the replication-defective retrovirus DEF27 (BM5d), pack aged as an amphotropic virus pseudotype, into C57BL/6J mice leads to d evelopment of murine AIDS. Disease development showed a long incubatio n period (20 to 24 weeks), was associated with amplification of the BM 5d provirus in splenocytes and lymph nodes, and was independent of the presence of exogenous or endogenous replication-competent helper viru ses. However, both the onset of disease and amplification of the defec tive provirus were significantly enhanced by coinfection with the repl ication-competent B-cell-tropic ecotropic helper virus BM5e. The part of the BM5d viral genome that was essential for the pathogenicity was determined by making precisely engineered alterations in the reading f rame of the gag and pol genes of BM5d proviral DNA and examining the a bility of the altered amphotropic BM5d pseudotypes to induce the disea se in C57BL/6J mice. The results show that expression of the MA (p15) and p12 regions of the gag gene is sufficient for pathogenicity of the BM5d retrovirus.