Electronic Thesis and Dissertation Repository

Thesis Format

Monograph

Degree

Doctor of Philosophy

Program

Microbiology and Immunology

Supervisor

Eric Arts J.

Abstract

Human immunodeficiency virus 1 (HIV-1) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pose significant public health challenges partly due to the limited understanding of their transmission. To improve our understanding of HIV-1 and SARS-CoV-2 transmission, we examined their unique transmission mechanisms and the impact of environmental factors on their spread, presenting a comprehensive analysis of the virus fitness and transmission dynamics. HIV is predominantly acquired sexually and – despite the numerous variants in an infected individual – new infections are established by a single viral variant, indicating a fitness advantage. To mimic this selection, we utilized ex vivo competition assays with transmitted/founder (T/F) viruses from penile-anal or penile-vaginal transmission, and T/F viruses from people who inject drugs (PWID), which were not subject to selection pressure crossing the genital mucosa. We discovered that T/F viruses from PWID exhibited a diminished transmission fitness through human cervical tissues to T helper type 1 (Th1) and Th17 cells. This diminished fitness was not observed in direct cell infections, suggesting a unique interplay with cervical tissue environments impacting transmission dynamics. Phenotypic assays showed that T/F from PWID had a higher tolerance to CCR5 (HIV-1 entry coreceptor) conformation diversity compared to other T/F viruses. Furthermore, T/F viruses had different levels of oligomannose-type glycans on the viral envelope protein, suggesting glycosylation plays a role in sexual transmission and blood transmission. To study the unique environmental attributes impacting SARS-CoV-2 transmission, we designed an aerosolization chamber to replicate human respiratory activities. By precise control of environmental conditions and various collection materials, we found that temperature, relative humidity and the presence of smoke particles do not significantly affect virus transmission. Our work challenges prior assumptions by demonstrating a shorter survival time of aerosolized droplets on various surfaces, informing more effective disinfection practices. By comparing the transmission characteristics of HIV-1 and SARS-CoV-2, this thesis sheds light on the complex effect of pathogen-host interactions and environmental influences on viral transmission. Our findings offer novel directions for HIV-1 vaccine development and underscore the importance of considering environmental factors in public health strategies to control the spread of pathogens via droplets.

Summary for Lay Audience

This research explores the transmission of two significant viruses with far-reaching health and socioeconomic impacts: HIV, the virus that causes AIDS, and SARS-CoV-2, the virus that causes COVID. Despite significant scientific progress, fully stopping these viruses has been challenging, largely due to gaps in our understanding of their transmission mechanisms. Our study aimed to shed light on how these viruses are passed between people with different risk activities. For HIV-1, our investigation focused on the initial viruses that manage to establish infections, known as transmitted/founder (T/F) viruses. These viruses differ in their ability to infect new hosts depending on the transmission route, such as through unprotected sex or drug injection. Specifically, our experiments using human cervical tissues to simulate penile-vaginal transmission showed that T/F viruses from individuals who inject drugs have a lower chance of establishing infection compared to those from individuals who engage in unprotected sex. This is probably due to the interaction between the virus's outer shell, or "envelope", and cervical tissues. On the other hand, we constructed a chamber that simulates how SARS-CoV-2 would travel through the air in real-life situations, such as when people talk, cough, or sneeze. We found that common environmental factors, such as temperature, humidity, and even smoke, have little impact on the virus's transmission. Additionally, our research into the virus's lifespan on different surfaces offers valuable information for public disinfection efforts. This analysis of HIV-1 and SARS-CoV-2 transmission enhances our understanding of viral spread and highlights the complex interactions between viruses, their hosts, and the environment. These insights pave the way for improved public health measures, such as the development of novel and more precise HIV-1 vaccines and strategies to curb the spread of respiratory viruses like SARS-CoV-2. Through this work, we aim to contribute to the global effort to mitigate the impacts of these viruses, offering hope for more effective control and prevention strategies.

Creative Commons License

Creative Commons Attribution-Share Alike 4.0 License
This work is licensed under a Creative Commons Attribution-Share Alike 4.0 License.

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Available for download on Friday, August 21, 2026

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