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Strategies to Facilitate the Eradica...

Mujib, Shariq.

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Strategies to Facilitate the Eradication of the HIV-1 Reservoir.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Strategies to Facilitate the Eradication of the HIV-1 Reservoir./
作者:	Mujib, Shariq.
出版者:	Ann Arbor : ProQuest Dissertations & Theses, : 2018,
面頁冊數:	302 p.
附註:	Source: Dissertations Abstracts International, Volume: 80-02, Section: B.
Contained By:	Dissertations Abstracts International80-02B.
標題:	Health sciences. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=10750077
ISBN:	9780438187559

Strategies to Facilitate the Eradication of the HIV-1 Reservoir.
Mujib, Shariq.

Strategies to Facilitate the Eradication of the HIV-1 Reservoir. - Ann Arbor : ProQuest Dissertations & Theses, 2018 - 302 p.

Source: Dissertations Abstracts International, Volume: 80-02, Section: B.

Thesis (Ph.D.)--University of Toronto (Canada), 2018.

This item must not be sold to any third party vendors.

Nearly 40 million individuals are currently living with Human Immunodeficiency Virus type 1 (HIV-1) infection globally and more than 70 million deaths can be attributed to the pathogen so far. HIV-1 primarily infects CD4 T cells leading to their widespread destruction that eventually manifests as Acquired Immunodeficiency Syndrome (AIDS), characterized by debilitating immune failure that gives rise to opportunistic malignancies resulting in death. Daily lifelong administration of antiretroviral therapy known as HAART is the only treatment for HIV-1 infection and adds several years of life if adherence is maintained; but treatment alone does not cure infection. However, despite HAART therapy, HIV-infected individuals exhibit chronic inflammation that is negatively associated with health outcomes. Additionally, mutations give rise to drug resistant viral strains. Therefore, developing a cure remains a top priority. However, HIV-1 constantly evades the immune response and establishes a persistent lifelong viral reservoir making it challenging to cure. In this thesis, I detail three unique strategies to facilitate eradication of the viral reservoir. Specifically, we demonstrated that HIV-1 Nef blockade enhanced the elimination of latently HIV-1-infected CD4 T cells by peptide-expanded autologous CD8 T cells. Nef blockade has never been tested as means to eradicate HIV-1 and represents a novel approach. We further demonstrated that expanded CD8 T cells more efficiently recognize autologous endogenous virus from CD4 T cells undergoing bryostatin-1-mediated virus reactivation in a "shock and kill" approach. Lastly, we discovered that bnAb recognition of HIV-1 envelopes on the surface of infected cells is highly variable and particularly the V1/V2 targeting bnAbs were capable of not only recognition of targets but of induction of antibody-mediated elimination of HIV-1-infected CD4 T cells. All experiments presented here were conducted on primary human cells for physiological relevance and in order to capture the ability of ex vivo immune cells to recognize and kill virus-infected cells. The next step with each of the proposed mechanisms to eliminate the viral reservoir is to assess their safety and efficacy in vivo in order to develop a cure against HIV/AIDS.

ISBN: 9780438187559Subjects--Topical Terms:

3168359
Health sciences.

Strategies to Facilitate the Eradication of the HIV-1 Reservoir.
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