Construction of an SIV/HIV type 1 chimeric virus with the human interleukin 6 gene and its production of interleukin 6 in monkey and human cells.
The switch from a Th1- to a Th2-type cytokine response is reported to be involved in human immunodeficiency virus (HIV) disease progression. To study the effect of IL-6, one of the Th2-type cytokines, on AIDS pathogenesis, we constructed an SIV/HIV-1 chimeric virus (SHIV) having the human IL-6 gene (SHIV-IL6) SHIV-IL6 could replicate in M8166, a human T cell line, as well as in monkey and human peripheral blood mononuclear cells (PBMCs). Along with the SHIV-IL6 replication, IL-6 was detected in the culture supernatant by ELISA. The maximum level of IL-6 was 35, 15, and 8 ng/ml in M8166, human PBMCs, and monkey PBMCs, respectively. The expressed IL-6 was biologically active as shown by the proliferation of IL-6-dependent murine hybridoma (MH-60) cells. The inserted IL-6 gene was stable for at least four passages (45 days after the initial infection) in M8166 cells, suggesting the ability to achieve stable expression of IL-6 in long-term experiments. Therefore, we successfully established an SHIV system expressing IL-6, and this is the first report of an SHIV expressing a Th2-type cytokine. With this system, IL-6 should be expressed in the regions where the virus replicates, and therefore the inoculation of macaque monkeys with SHIV-IL6 is expected to provide further information on the etiology of AIDS.
Haga
T
T
Laboratory of Viral Pathogenesis, Institute for Virus Research, Kyoto University, Japan.
Kuwata
T
T
Kozyrev
I
I
Kwofie
T B
TB
Hayami
M
M
Miura
T
T
D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004797:Enzyme-Linked Immunosorbent Assay; D005822:Genetic Vectors; D015497:HIV-1 / Q000235:genetics; D000882:Haplorhini; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics*; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000821:virology; D016133:Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000096:biosynthesis; D015302:Simian Immunodeficiency Virus / Q000235:genetics* / Q000254:growth & development; D014779:Virus Replication
D015850:Interleukin-6; D011994:Recombinant Proteins