Benedikt Strunz [1,*], Julia Hengst [1,2,*], Katja Deterding [2], Michael P. Manns [2], Marcus Cornberg [2], Hans-Gustaf Ljunggren [1], Heiner Wedemeyer [2], Niklas K. Björkström [1]
Affiliates: [1] Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden. [2] Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.

Diversity is a central requirement for the immune system’s capacity to adequately clear a variety of different infections. As such, NK cells represent a highly diverse population of innate lymphocytes important in the early response against viruses. Yet, the extent to which a chronic pathogen affect NK cell diversity is largely unknown. We studied this issue in the context of chronic HCV infection, using novel metrics to estimate immune system diversity. High-dimensional flow cytometer-based assays combined with stochastic neighbor embedding analysis revealed that chronic HCV infection caused a significant imprint on the human NK cell compartment. Furthermore, the infection resulted in increased inter-individual, but decreased intra-individual, diversity. The effect of chronic HCV infection on the NK cell compartment appeared largely irreversible, since it persisted long after successful interventional clearance of the virus. Taken together, our results provide detailed insights into how an infection’s history affects human NK cell diversity.