Dynamics of the blood plasma proteome during hyperacute HIV-1 infection

HIV-1 remains incurable and there is no effective vaccine towards the infection. A main challenge for this is the lack of a holistic understanding of the myriad of complex virus-host interactions during hyperacute HIV-1 infection (hAHI), and how these contribute to tissue damage and pathogenesis. Here, 1293 blood plasma proteins were quantified from 157 linked plasma samples collected before, during, and after hAHI of 54 volunteers from four sub-Saharan African countries. Six distinct longitudinal expression profiles were identified, of which four demonstrated a consistent decrease in protein levels following HIV-1 infection. Differentially expressed proteins were involved in inflammation, innate immunity, cell motility, and actin cytoskeleton reorganisation. Specifically, decreased levels of Zyxin, Secretoglobin family 1A member 1, and Pro-platelet basic protein were associated with acute retroviral syndrome; Rho GTPase activating protein 18, Annexin A1, and Lipopolysaccharide binding protein with viral load; and Hepsin, Protein kinase C beta, and Integrin subunit beta 3 with disease progression. This is the first holistic characterisation of within-patient blood plasma proteome dynamics during the first weeks of HIV-1 infection and presents multiple potential blood biomarkers and targets for prophylactic and therapeutic HIV-1 interventions.