Honors Theses

Date of Award

Spring 4-23-2021

Document Type

Undergraduate Thesis

Department

Biology

First Advisor

Ziaeddin Shariat-Madar

Second Advisor

John Rimoldi

Third Advisor

James Stewart

Relational Format

Dissertation/Thesis

Abstract

Human Immunodeficiency Viruses are a group of lentiviruses that have seen a lot of study ever since their discovery. HIV-1, the most common and virulent form of the virus, has proven to be quite deadly when untreated, so any research into the mechanisms of HIV pathogenesis and replication could have major medical applications all over the world. HIV-1 is a sexually transmitted virus that compromises the hosts immune system and eventually leads to the patient developing AIDS, a life-threatening condition that nearly half of people infected with HIV will develop within ten years. Our study sets out to determine exactly how HIV-1 is able to facilitate its own spread through the use of its viral proteins and genome. The protein we focus on in this study is the Tat protein. Tat is short for Trans-Activator of Transcription. It gets this name from the role that the protein plays in the facilitation of the transcription of the viral genome once it invades a host cell. It performs this role by binding to the RNA stem-loop structure known as TAR located at the 5’ end of HIV-1 transcripts. Once bound, Tat assists in recruiting additional transcriptional elements, increasing the transcription of viral RNA. We seek to determine whether the presence of tat also influences the mechanisms of blood coagulation in the body such as the contact activation pathway and the kallikrein-kinin system, due to the high amount of cardiovascular ailments that are often associated with HIV. ` We decided to conduct a time course using the plasma of HIV-1 transgenic mice to see if the presence of Tat protein in the plasma would affect the production of kallikrein and its other downstream products in the kallikrein kinin system. One of these byproducts, bradykinin, has also been implicated in altering endothelial structure and the compromise of vascular selectivity and permeability. This alteration in selectivity associated with bradykinin may play a role in allowing HIV virus particles to more easily spread to other cells and also to cross the blood brain barrier, compromising the brain to HIV infection. The results of the study showed that the presence of Tat is indeed associated with higher levels of kallikrein activity in the plasma compared to when Tat is absent. We also found that Tat+ plasma contains a higher level of kallikrein itself, indicating that the byproduct, bradykinin, is also being produced at a higher level. These higher levels of kallikrein activity and increase in kallikrein production, signal that the presence of Tat protein is leading to higher rates of reaction in the kallikrein-kinin system, indirectly resulting in the production of excess bradykinin and also the compromise of endothelial cells.

Creative Commons License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

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