| 研究実績の概要 |
Results showed iPS-ML derived macrophages are useful as a good model for investigating host/HIV-1 interaction in myeloid cells. Analysis of APOBEC3 family protein in iPS-ML cell showed differential expression of individual proteins (for example: A3A, A3G, A3F), and more importantly some cell lines express stable haplotypes of A3H. Furthermore, A3 proteins (specially A3G A3F) induced HIV-1 restriction in iPS-ML derived macrophages. This restriction is counteracted by the HIV-1 viral factor Vif.
As A3 poteins mediate HIV-1 restriction via inducing lethal mutations to HIV-1 genome, G- to -A mutations are signifcantly detected in the Vif-deficient HIV-1-infected iPS-ML cells. However, deaminase-independent mechanisms (no viral mutations) to restrict HIV-1 in iPS-ML cells are also suggested.
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| 今後の研究の推進方策 |
Future work will focus on determining the possible mechanisms to induce HIV-1 restriction in iPS-MLderived macrophages.
- analysis for A3-mediated viral mutations to identify frequency, magnitude and preferred sequences of A3 proteins to induce such restriction.
- analysis for HIV-1 reverse transcription (RT) and late RT products in order to clarify deaminase independent restriction.
- Creating modified iPS-ML derived macrophages (A3G deleted, A3F deleted, or A3A-A3G deleted cells), which will characterize the potential role of each individual protein to mediate HIV-1 restriction, as well as testing the potential to utilze A3-mediated mutagenesis to attain HIV-1 functional cure.
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