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 cells from Th1-producing cells to Th2-producing cells. To determine whether this 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 human IL-5 was inserted into vpr-deleted and nef-deleted infectious SHIVs. The obtained replication-competent viruses were used to infect human T-cell lines and monkey peripheral blood mononuclear cells. As a result, at the time of peak NI-IL5 virus production, IL-5 was produced with a significantly higher titer than 3sj-IL5. The functionality of the produced IL-5 was confirmed by IL-5-dependent cells. The replication of both SHIVs having IL-5 appeared to be faster than that of the parental viruses without the IL-5 gene. These 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 effect on viral replication and pathogenicity in vivo.
Kozyrev
I L
IL
Laboratory of Viral Pathogenesis, Institute for Virus Research, Kyoto University, Japan.
Miura
T
T
Haga
T
T
Kuwata
T
T
Hayami
M
M
D000163:Acquired Immunodeficiency Syndrome / Q000209:etiology / Q000276:immunology; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002478:Cells, Cultured; D002678:Chimera / Q000235:genetics* / Q000276:immunology* / Q000502:physiology; D017931:DNA Primers / Q000235:genetics; D015754:Genes, nef; D016334:Genes, vpr; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology* / Q000472:pathogenicity / Q000502:physiology; D006801:Humans; D015848:Interleukin-5 / Q000096:biosynthesis / Q000235:genetics*; D008253:Macaca mulatta; D015302:Simian Immunodeficiency Virus / Q000235:genetics* / Q000276:immunology* / Q000472:pathogenicity / Q000502:physiology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014774:Virulence / Q000235:genetics / Q000276:immunology; D014779:Virus Replication
D017931:DNA Primers; D015848:Interleukin-5