Transcriptomic profiling of peripheral blood NK cells of chronic HBV, HCV and HIV patients

Background: NK cells during chronic viral infection have been well studied over the last decade. We performed an unbiased next-generation RNA-sequencing approach to identify commonalities or differences of the effect of HIV, HCV and HBV viremia on NK cell transcriptomes. Methods: Using cell sorting, we obtained CD3-CD56+ NK cells from blood of 6 HIV, 11 HCV, and 32 HBV infected and untreated patients. Library preparation and sequencing were done using Illumina mRNA-Seq Sample Prep Kit and the HiSeq 2000, HiSeq2500 or NextSeq 500, and further analysis by an in-house analytic pipeline. Results: In NK cells from HIV, HCV and HBV patients, transcriptome analysis identified 272, 53, and 56 differentially expressed genes, respectively (fold change >1.5, q-value 0.2). Interferon stimulated genes were induced in NK cells from HIV/HCV patients, but not during HBV infection. HIV viremia downregulated ribosome assembly genes in NK cells. In HBV, viral load and ALT variation had little effect on genes related to NK effector function. Conclusion: We compare, for the first time, NK cell transcripts of viremic HIV, HCV and HBV patients. We clearly demonstrate distinctive NK cell gene signatures in 3 different populations, suggestive for a different degree of functional alterations of the NK cell compartment as compared to healthy individuals. Overall design: We analyzed NK cell transcripts collected from the blood of well-characterized chronic HBV patients (n=32), chronic HCV patients (n=8), and HIV patients (n=6). Differential gene expression analysis, global module analysis, and unsupervised clustering analysis were performed by employing RNA-sequencing on blood NK cell transcriptomes.

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Boeijen LL, Hou J, de Groen RA, Verbon A, Boonstra A