Dissecting the host determinants of flavivirus infection using QIC-seq

Area of Science:

• Virology
• Molecular Biology
• Genetics

Background:

• Flaviviruses cause diverse diseases, but cellular mechanisms and host responses are poorly understood.
• Host-pathogen interactions are key to understanding flavivirus pathology.

Purpose of the Study:

• To systematically compare host factor requirements for flaviviruses using a novel single-cell approach.
• To analyze host transcriptional responses to flaviviral infection.

Main Methods:

• Developed and applied Quantification of Infection and CRISPR guide sequencing (QIC-seq).
• Combined CRISPR/Cas9 knockout with virus-inclusive transcriptomics.
• Systematically compared host factor dependencies and transcriptional responses.

Main Results:

• Dengue and yellow fever viruses depend on oligosaccharyltransferase complex subunits.
• West Nile and Langat viruses depend on ER-associated degradation machinery.
• Observed virus-induced upregulation of interferon-stimulated genes and unfolded protein response.

Conclusions:

• QIC-seq enables quantitative comparison of viral host factor utilization.
• Findings provide insights into distinct flavivirus replication strategies.
• Data may inform the development of host-directed antiviral therapies.