The host
eIF4F translation initiation complex plays a critical role the translation of capped mRNAs. Although human cytomegalovirus (HCMV)
infection increases the abundance and activity of the host
eIF4F complex, the requirement for
eIF4F components in HCMV replication and mRNA translation has not been directly tested. In this study, we found that decreasing the abundance or activity of
eIF4F from the start of
infection inhibits HCMV replication. However, as
infection progresses, viral mRNA translation and replication becomes increasingly resistant to
eIF4F inhibition. During the late stage of
infection the association of representative immediate-early, early, and late mRNAs with polysomes was not affected by
eIF4F disruption. In contrast,
eIF4F inhibition decreased the translation of representative host eIF4F-dependent mRNAs during the late stage of
infection. A global analysis of the translation efficiency of HCMV mRNAs during the late stage of
infection found that
eIF4F disruption had a minimal impact on the association of HCMV mRNAs with polysomes but significantly diminished the translation efficiency of eIF4F-dependent host transcripts. Together, our data show that the translation of host eIF4F-dependent mRNAs remains dependent on
eIF4F activity during HCMV
infection. However, during the late stage of
infection the translation efficiency of viral mRNAs does not correlate with the abundance or activity of the host
eIF4F complex.