Dissecting Host-Viral Interactons Through Focused or Unbiased High-Throughput Genetic Approaches

<p>In the world around us, viruses surround and vastly outnumber us. Indeed, there are roughly 1 sextillion—or one thousand million million million—times as many viral particles as humans on earth (1). While most of these viruses do not cause disease in humans, those that do present a grave and increasing threat to human health. Fundamental studies in host-viral interactions are thus critical to further our understanding of the parameters of viral infection and elucidate potential new treatments. Since, as obligate intracellular parasites, viruses rely on host resources at every step of the viral lifecycle, in-depth knowledge of how viruses hijack human proteins, and how cells have evolved defense mechanisms to prevent this, can reveal insights with potential therapeutic relevance. In my graduate work, I employed a variety of approaches—targeted mutagenesis and loss of function studies, genome-scale CRISPR screens, and focused CRISPR screens—to gain mechanistic insight of host-viral interactions, focusing on the human immunodeficiency virus type 1 (HIV-1) and the human coronaviruses (HCoVs). I begin this thesis by providing an overview of the viral lifecycle and highlighting the potential utility of targeting each step in the viral lifecycle for therapeutic purposes, exemplified by current FDA-approved therapies. I continue by examining the utility of each of three major methodologies I utilized in my thesis for uncovering new insights with potential significance for designing novel antiviral approaches. Next, I recount the mechanistic insights gained by studies performed in my thesis work using these approaches. Finally, I conclude by discussing potential therapeutic relevance of the insights uncovered by this thesis work.</p>

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Thesis

Year

2023

Author dc:creator

• Poston, Daniel

Contributors dc:contributor

• Paul Bieniasz

• HIV-1
• human coronaviruses
• host-viral interactions
• CRISPR-Cas
• antiviral therapy
• virus lifecycle
• Life Sciences

Repository record dc:identifier

https://digitalcommons.rockefeller.edu/student_theses_and_dissertations/727

OAI identifier oai:identifier

oai:digitalcommons.rockefeller.edu:student_theses_and_dissertations-1731