By engineering human cytomegalovirus to express single guide RNA libraries directly from the viral genome, the virus-encoded CRISPR-based direct readout screening (VECOS) facilitates profiling of different stages of viral infection in a pooled format.
VECOS identified hundreds of host dependency and restriction factors affecting viral genome replication and particle secretion, emphasizing late viral stages regulating viral particle quality over quantity.
This approach provides a multi-dimensional understanding of virus-host interactions, highlighting that correct virion assembly, heavily reliant on virus-host interactions, is a critical stage in the human cytomegalovirus life cycle.
VECOS enables systematic high-resolution dissection of human protein roles during infection cycles, paving the way for in-depth studies of host-herpesvirus interactions.
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