Construction of SIV/HIV-1 chimeric viruses having the IL-5 gene and determination of their ability to replicate and produce IL-5

During the progression of AIDS, there is a shift in abundance of immune cel ls from Th1-producing cells to Th2-producing cells. To determine whether th in change might have an effect on HIV-1 replication in vivo, we constructed simian/human immunodeficiency chimeric viruses having the human IL-5 gene (a Th2-type cytokine) and examined the effect of the inserted gene on viral replication, IL-5 production and viral stability in vitro. The DNA of huma n IL-5 was inserted into vpr-deleted and nef-deleted infectious SHIVs. The obtained replication-competent viruses were used to infect human T-cell lin es and monkey peripheral blood mononuclear cells. As a result, at the time of peak NI-ILS virus production, IL-5 was produced with a significantly hig her titer than 3sj-IL5. The functionality of the produced IL-5 was confirme d by IL-5-dependent cells. The replication of both SHIVs having IL-5 appear ed to be faster than that of the parental viruses without the IL-5 gene. Th ese results show that co-expression of IL-5 stimulates SHIV replication in vitro. Thus, it is expected that expression of IL-5 will also have an effec t on viral replication and pathogenicity in vivo.