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  1. 參加對象:高雄醫學大學全校師生
  2. 授課教師:Vineet N. KewalRamani ( 美國國家癌症研究院HIV抗藥性資深研究員 )
  3. 授課日期,時間,地點及授課主題如下:
    10/15 (星期三) 8:00~12:00 國研2樓 IR203
    HIV-1 Capsid Shields Viral DNA from the Cytosolic DNA Sensor cGAS (1)
    10/15 (星期三) 14:00~17:00 國研2樓 IR203
    HIV-1 Capsid Shields Viral DNA from the Cytosolic DNA Sensor cGAS (2)
  4. 課程大綱

    Retroviruses must replicate their genomes in the presence of cytosolic DNA sensors capable of triggering an antiviral response. Here we demonstrate that HIV-1 reverse transcribed DNA products are shielded from cytosolic DNA sensors by the HIV-1 core. Treatment of HIV-1 infected cells with the capsid-binding drug PF-3450074 releases DNA products into the cytosol where they can stimulate the cGAS-STING pathway and produce a type I IFN response. HIV-1 coordinates reverse transcription and uncoating to minimize exposure of DNA products, and perturbation of either process can influence the ability of HIV-1 to induce a type I IFN response. Furthermore, we demonstrate that the N74D mutation in the viral capsid, which is detrimental to reverse transcription in primary macrophages, can be rescued by destabilizing the viral core. Both wild-type and N74D HIV-1 stimulate an antiviral response in macrophages that is dependent on viral DNA synthesis and impedes subsequent rounds of virus infection. Collectively, these results illustrate the interdependence of reverse transcription and uncoating, and the importance of coordinating these two viral activities to avoid immune stimulation.

主辦單位:醫學檢驗生物技術學系

協辦單位: 傳染病與癌症研究中心

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