Genetics and Infectious Diseases: From Host Transcriptome of HIV Infection to Bioethical Considerations in International Cohorts

Abstract

Host genetic research has fueled infectious disease discoveries, including for HIV-1, from early candidate gene studies to recent multi-omics efforts. It offers opportunities for a more comprehensive understanding of infection and pathogenesis, which may elucidate targets for new preventive and therapeutic interventions. The first two aims of this dissertation analyze the host transcriptome to understand the HIV acquisition and treatment response: Chapter 2 aims to identify genes and pathways associated with extreme HIV-1 susceptibility phenotypes; Chapter 3 aims to identify a signature of interferon-stimulated gene expression that differentiates people living with HIV-1 who are virally suppressed on antiretroviral treatment from HIV-uninfected individuals. Many of the host genetic research on infectious diseases are multinational collaborations. Participants are recruited from culturally diverse environments, e.g., Africa, where bioethics issues need to be considered to better safeguard participants’ autonomy and voluntary participation. The third aim of this dissertation, described in Chapter 4, explores ethical, legal, and social implication issues raised in the consent process of genetic research conducted in international settings.