2011 Fiscal Year Final Research Report
Analysis of Cellular Factors Regulating HIV-1 Infection in Small Animals
| 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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| Keywords | APOBEC1 / HIV-1 / 脱アミノ化 / leucine-rich motif / dimerization |
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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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[Presentation] Intrinsic Restriction Activity by APOBEC1 against the Mobility of Autonomous Retrotransposons2010
Author(s)
Ikeda T, Abd El Galil KH, Tokunaga K, Maeda K, Sata T, Sakaguchi N, Heidmann T, and Koito A.
Organizer
Cold Spring Harbor Laboratory Meeting, Retroviruses
Place of Presentation
Cold Spring Harbor Laboratory, New York, USA
Year and Date
20100524-29
