Comparative Analysis of HIV-1 and SARS-CoV-2 Transmission Dynamics: Investigating Viral Fitness, Environmental Factors, and Pathogen-Host Interactions

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.