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Primary cells culturedin vitro currently provide the highest available relevance for examining molecular and genetic requirements for the establishment, maintenance, and reactivation of HCMV latency. However, their expense, heterogeneity, and intransigence to both long-term culture and molecular or genetic modification create rigor and reproducibility challenges for HCMV latency studies. There are several cell line models for latency not obstructed by deficiencies inherent in primary cells. However, many researchers view cell line studies of latency to be physiologically irrelevant because of the perception that these models display numerous and significant differences from primary cells. Here, we show that the very first step in a latent HCMV infection, entry of the virus into cells, occurs in cell line models in a manner indistinguishable from that in which it occurs in primary CD34+ hematopoietic progenitor cells. Our data argue that experimental HCMV latency is much more similar than it is different in cell lines and primary cells.

Cell Line Models for Human Cytomegalovirus Latency Faithfully Mimic Viral Entry by Macropinocytosis and Endocytosis