Sun, Bo; da Costa, Kelly AS; Alrubayyi, Aljawharah; Kokici, Jonida; Fisher-Pearson, Natasha; Hussain, Noshin; D'Anna, Stefano; ... Peppa, Dimitra; + view all Sun, Bo; da Costa, Kelly AS; Alrubayyi, Aljawharah; Kokici, Jonida; Fisher-Pearson, Natasha; Hussain, Noshin; D'Anna, Stefano; Piermatteo, Lorenzo; Salpini, Romina; Svicher, Valentina; Kucykowicz, Stephanie; Ghosh, Indrajit; Burns, Fiona; Kinloch, Sabine; Simoes, Pedro; Bhagani, Sanjay; Kennedy, Patrick TF; Maini, Mala K; Bashford-Rogers, Rachael; Gill, Upkar S; Peppa, Dimitra; - view fewer (2024) HIV/HBV co-infection remodels the immune landscape and Natural Killer cell ADCC functional responses. Hepatology 10.1097/HEP.0000000000000877. (In press).

Text hiv_hbv_co_infection_remodels_the_immune_landscape.870.pdf - Accepted Version Access restricted to UCL open access staff until 1 May 2025. Download (1MB)

Abstract

BACKGROUND: HBV and HIV co-infection is a common occurrence globally, with significant morbidity and mortality. Both viruses lead to immune dysregulation including changes in NK cells, a key component of antiviral defense and a promising target for HBV cure strategies. Here we used high-throughput single cell analysis to explore the immune cell landscape in people with HBV mono-infection and HIV/HBV co-infection, on antiviral therapy, with emphasis on identifying the distinctive characteristics of NK cell subsets that can be therapeutically harnessed. RESULTS: Our data show striking differences in the transcriptional programs of NK cells. HIV/HBV co-infection was characterized by an overrepresentation of adaptive, KLRC2 expressing NK cells, including a higher abundance of a chemokine enriched (CCL3/CCL4) adaptive cluster. The NK cell remodeling in HIV/HBV co-infection was reflected in enriched activation pathways, including CD3ζ phosphorylation and ZAP-70 translocation that can mediate stronger ADCC responses and a bias towards chemokine/cytokine signaling. By contrast HBV mono-infection imposed a stronger cytotoxic profile on NK cells and a more prominent signature of 'exhaustion' with higher circulating levels of HBsAg. Phenotypic alterations in the NK cell pool in co-infection were consistent with increased 'adaptiveness' and better capacity for ADCC compared to HBV mono-infection. Overall, an adaptive NK cell signature correlated inversely with circulating levels of HBsAg and HBV-RNA in our cohort. CONCLUSIONS: This study provides new insights into the differential signature and functional profile of NK cells in HBV and HIV/HBV co-infection, highlighting pathways that can be manipulated to tailor NK cell-focused approaches to advance HBV cure strategies in different patient groups.

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