To assess the contribution of these proteins to overall HCMV replication, mutants containing deletions of IRS1 and TRS1 both individually and in tandem were used to show that loss of either gene product in isolation did not strongly affect viral growth, but infection with an IRS1/TRS1 double deletion mutant resulted in an extreme reduction in protein synthesis and failure to replicate in primary human fibroblasts [65]. Here, IRS1 is linked to infection.