자료유형 | 학위논문 |
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서명/저자사항 | Properties of HIV-1 Env and Human Seminal Fluid That Determine Virus Inhibition by Antibodies and Microbicides. |
개인저자 | Johnson, Jacklyn. |
단체저자명 | The University of Iowa. Microbiology. |
발행사항 | [S.l.]: The University of Iowa., 2019. |
발행사항 | Ann Arbor: ProQuest Dissertations & Theses, 2019. |
형태사항 | 206 p. |
기본자료 저록 | Dissertations Abstracts International 81-04B. Dissertation Abstract International |
ISBN | 9781088368596 |
학위논문주기 | Thesis (Ph.D.)--The University of Iowa, 2019. |
일반주기 |
Source: Dissertations Abstracts International, Volume: 81-04, Section: B.
Advisor: Haim, Hillel. |
이용제한사항 | This item must not be sold to any third party vendors.This item must not be added to any third party search indexes. |
요약 | Human immunodeficiency virus type 1 (HIV-1) establishes a persistent infection that leads to acquired immunodeficiency syndrome (AIDS). Approximately 36 million people worldwide are living with HIV-1, which is commonly acquired through sexual contact. Antiviral therapies control disease progression, but do not eliminate this virus from the host. Thus, global efforts are focused on developing vaccines that prevent HIV-1 transmission. Such vaccines are based on eliciting the production of protective antibodies that target the envelope glycoproteins (Envs) of this virus. Unfortunately, HIV-1 immunization trials have shown limited efficacy. A better understanding of the antibody-mediated inactivation process is needed to improve vaccine strategies. In this work we describe two novel factors that contribute to HIV-1 inactivation. First, we show that structural stability of the Env protein determines its sensitivity to vaccine-elicited antibodies. Different interactions within Env contribute to its stability. Perturbation of the Env-stabilizing interactions by physical and chemical treatments enhances sensitivity of HIV-1 to antibodies. Second, we found that the chemical composition of the transmission medium affects Env inhibition by antibodies and other inhibitory agents. Semen is the most common vehicle for HIV-1 transmission. This medium contains high concentrations of the sugar fructose. We found that semen fructose competitively blocks binding of antiviral agents that target sugar residues on Env. Together, this work advances our understanding of the mechanism that underlies HIV-1 inactivation by vaccine-elicited antibodies and provides novel strategies to enhance their potency. |
일반주제명 | Virology. Pharmacology. |
언어 | 영어 |
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