Doctoral Degrees (Virology)

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HIV cell-to-cell spread leads to a differential transcriptional response and slows evolution of drug resistance relative to cell-free infection.
(2020) Hunter, Jessica Rose.; Sigal, Alexander.
HIV transmits between hosts but also transmits between cells in the same host. How this latter, cellular transmission occurs has been the subject of extensive study. Yet why HIV transmits between cells using two different infection modes: cell-to-cell spread and cell-free infection, is not clearly understood. This is because cell-to-cell spread is a more efficient mode of infection, where the virus is able to be successfully transmitted between cells despite natural inhibitors such as antibodies. Here, using in vitro experimentation, I have determined some of the implications of cell-to-cell spread of HIV for cell death, evolution, and inflammation. I have discovered potential costs to this infection mode, such as increased cell death, slowed evolution of resistance, and an increased interferon response which may interfere with viral replication. Hence, costs associated with cell-to-cell spread may prevent it being the dominant infection mode in cellular transmission.