Emil Johansson will defend his thesis: Virus-host interactions in HIV-1 and HIV-2 infections.
Date: 2023-05-17
Time: 13:00
Place: Agardh lecture hall, CRC, Jan Waldenströms gata 35, Malmö or
you can join by Zoom, https://lu-se.zoom.us/j/64703958604
Opponent: docent Ujjwal Neogi, Stockholm
Virus-host interactions in HIV-1 and HIV-2 infections.
Summary:
Human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2) are the two causative agents of AIDS. HIV-1 is responsible for the HIV pandemic, while HIV2 is primarily confined to West Africa. Although HIV-1 and HIV-2 share several characteristics, such as route of transmission, is HIV-2 less pathogenic than HIV-1. The asymptomatic disease stage in treatment naïve individuals is approximately twice as long among in people living with HIV-2 (PLWH2) compared to in people living with HIV-1 (PLWH1). The underlying mechanisms behind this difference are unknown but may be attributed to a more effective immune response in HIV-2 compared to in HIV-1 infection. Moreover, although most PLWH2 display low to undetectable plasma viral loads (pVL), in general they still do progress towards AIDS in the absence of antiretroviral treatment – albeit at a slower rate. The objectives of this thesis were to characterise virus-host interactions in PLWH1 and PLWH2, and to investigate the associations of these interactions with different traits of disease progression. More specifically to study: 1) the impact of HIV-2 viraemia on CD8+ T cell and B cell phenotypes, and plasma proteomes; and 2) associations between plasma proteome signatures and HIV disease progression. To do this, we immunophenotyped CD8+ T-cells and B-cells using flow cytometry and bioinformatics. We observed that both viraemic and aviraemic HIV2 infection promoted CD8+ T-cells exhaustion and induced an expansion of hyperactivated B-cells as well as high levels of the T helper 1 cell-associated transcription factor T-bet. We also utilised a novel analysis pipeline of dataindependent acquisition mass-spectrometry (DIA-MS) to determine the proteome in blood plasma. The analysis showed alterations of plasma proteins that were associated with frequencies of terminally exhausted CD8+ T-cells and hyperactivated B-cells. Next, we used the same DIA-MS approach on archived plasma collected within three years of the estimated date of HIV-1 or HIV-2 infection. The analysis indicated that increased release of proteins from sigmoid colon and spleen tissue was associated with depletion of CD4+ T-cells, and that the expression profile of ten specific proteins, found to be associated with CD4+ T-cell loss, could distinguish faster from slower disease progression. In summary, increased understanding of how HIV-host interactions dictate viraemia and disease progression rate provides important insights about HIV-1 and HIV-2 pathogenesis that may open up new directions for developing HIV therapeutic and prophylactic strategies.