PT  - JOURNAL ARTICLE
AU  - Zhiyuan Yao
AU  - Fabio Zanini
AU  - Sathish Kumar
AU  - Nuttada Panpradist
AU  - Avery Muniz
AU  - Stephen R. Quake
AU  - Shirit Einav
TI  - The transcriptional landscape of Venezuelan equine encephalitis virus infection
AID  - 10.1101/2020.02.18.955393
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.02.18.955393
4099  - http://biorxiv.org/content/early/2020/02/25/2020.02.18.955393.short
4100  - http://biorxiv.org/content/early/2020/02/25/2020.02.18.955393.full
AB  - No vaccines or antivirals are approved against Venezuelan equine encephalitis virus (VEEV) infection in humans. To improve our understanding of VEEV-host interactions, we simultaneously profiled host transcriptome and viral RNA (vRNA) in thousands of single cells during infection of human astrocytes. Host transcription was suppressed, and “superproducer cells” with extreme vRNA abundance and altered transcriptome emerged during the first viral life cycle. Cells with increased structural-to-nonstructural transcript ratio demonstrated upregulation of trafficking genes at later time points. Loss- and gain-of-function experiments confirmed pro- and antiviral host factors. Single-cell deep sequencing analysis identified a viral E3 protein mutation altering host gene expression. Lastly, comparison with data from other viruses highlighted common and unique pathways perturbed by infection across evolutionary scales. This study provides a high-resolution characterization of the cellular response to VEEV infection, identifies candidate targets for antivirals, and establishes a comparative single-cell approach to study the evolution of virus-host interactions.