| Project/Area Number |
22890144
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Single-year Grants |
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| Research Field |
Virology
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| Research Institution | Kumamoto University |
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Principal Investigator |
IKEDA Terumasa 熊本大学, 大学院・生命科学研究部, 学術研究員 (00588410)
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| Project Period (FY) |
2010 – 2011
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| Project Status |
Completed (Fiscal Year 2011)
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| Budget Amount *help |
¥3,146,000 (Direct Cost: ¥2,420,000、Indirect Cost: ¥726,000)
Fiscal Year 2011: ¥1,508,000 (Direct Cost: ¥1,160,000、Indirect Cost: ¥348,000)
Fiscal Year 2010: ¥1,638,000 (Direct Cost: ¥1,260,000、Indirect Cost: ¥378,000)
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| Keywords | APOBEC1 / HIV-1 / 脱アミノ化 / leucine-rich motif / dimerization / dimerization domain |
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| Research Abstract |
APOBEC1(A1) is the catalytic component of a complex that mediates C-to-U deamination of mRNA for apolipoprotein B(apoB), and is involved in lipid transport in gastrointestinal tissues. However, various mammalian A1s are also potent DNA C-to-U deaminases, suggesting possible innate immune functions. We previously reported that A1s from rodents(mouse, rat and hamster) and lagomorphs(rabbit) are capable of inhibiting the infectivity of HIV-1. A rank order in anti-HIV-1 potency was seen with rabbit A1 showing greatest activity. In contrast, human A1 did not show any anti-HIV-1 activity. To determine the region responsible for rabbit A1 anti-HIV-1 activity, we constructed 14 chimeras of human and rabbit A1 using overlapping PCR and tested them against HIV-1 using single-round infectivity assays. Results showed that the C-terminal region containing a leucine-rich motif and two putative dimerization domains is important for anti-HIV-1 activity. A1 chimeras showing anti-HIV-1 activity tended to be incorporated into HIV-1 virions more efficiently and these chimeras induced higher G-to-A and C-to-T mutations in the viral DNA and RNA. Taken together, these findings suggest that the C-terminal region containing a leucine-rich motif and dimerization domains are involved in both packaging into the HIV-1 virion and deamination activity. These findings may be applicable to understanding the roles of the broader APOBEC family in virus restriction.
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