Redefining De Novo Gammaherpesvirus Infection Through High-Dimensional, Single-Cell Analysis of Virus and Host

Published: Aug. 11, 2020, 4:04 p.m.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.11.203117v1?rss=1 Authors: Berger, J. N., Sanford, B., Kimball, A. K., Oko, L. M., Kaspar, R. E., Niemeyer, B. F., Jones, K. L., Clambey, E. T., van Dyk, L. F. Abstract: Virus infection is frequently characterized using bulk cell populations. How these findings correspond to infection in individual cells remains unclear. Here, we integrate high-dimensional single-cell approaches to quantify viral and host RNA and protein expression signatures using de novo infection with a well-characterized model gammaherpesvirus. While infected cells demonstrated genome-wide transcription, individual cells revealed pronounced variation in gene expression, with only 9 of 80 annotated viral open reading frames uniformly expressed in all cells, and a 1000-fold variation in viral RNA expression between cells. Single-cell analysis further revealed positive and negative gene correlations, many uniquely present in a subset of cells. Beyond variation in viral gene expression, individual cells demonstrated a pronounced, dichotomous signature in host gene expression, revealed by measuring host RNA abundance and post-translational protein modifications. These studies provide a resource for the high-dimensional analysis of virus infection, and a conceptual framework to define virus infection as the sum of virus and host responses at the single-cell level. Copy rights belong to original authors. Visit the link for more info