• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

APOBEC3 family proteins mediate HIV-1 restriction in myeloid cells

Research Project

Project/Area Number 22K16375
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 54030:Infectious disease medicine-related
Research InstitutionKumamoto University

Principal Investigator

ELSAYED.NASSER HESHAM  熊本大学, ヒトレトロウイルス学共同研究センター, 特任助教 (20868020)

Project Period (FY) 2022-04-01 – 2025-03-31
Project Status Granted (Fiscal Year 2023)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2024: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2023: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2022: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
KeywordsHIV-1 restriction
Outline of Research at the Start

Proposed plan is outlined to be conducted within tow years. First plan is conducted in one year, and Plane B is conducted in the second year. Plane C will be conducted alongside other plans.
By third year, it is excepected to conclude all results and prepare paper for publication.

Outline of Annual Research Achievements

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.

Current Status of Research Progress
Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

Currently, one more staff joined this research project, which provided better handling of the planned investigations.

Strategy for Future Research Activity

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.

Report

(2 results)
  • 2023 Research-status Report
  • 2022 Research-status Report
  • Research Products

    (2 results)

All 2023 2022

All Journal Article (2 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 1 results,  Open Access: 2 results)

  • [Journal Article] APOBEC3 degradation is the primary function of HIV-1 Vif for virus replication in the myeloid cell line THP-12023

    • Author(s)
      Ikeda Terumasa、Shimizu Ryo、Nasser Hesham、Carpenter Michael A、Cheng Adam Z、Brown William L.、Sauter Daniel、Harris Reuben S
    • Journal Title

      bioRxiv

      Volume: -

    • DOI

      10.1101/2023.03.28.534666

    • Related Report
      2022 Research-status Report
    • Open Access / Int'l Joint Research
  • [Journal Article] Inhibitory and Stimulatory Effects of IL-32 on HIV-1 Infection2022

    • Author(s)
      Nasser Hesham、Takahashi Naofumi、Eltalkhawy Youssef M.、Reda Omnia、Lotfi Sameh、Nasu Kanako、Sakuragi Jun-ichi、Suzu Shinya
    • Journal Title

      The Journal of Immunology

      Volume: 209 Issue: 5 Pages: 970-978

    • DOI

      10.4049/jimmunol.2200087

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research

URL: 

Published: 2022-04-19   Modified: 2024-12-25  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi