Human Cytomegalovirus Enters the Primary CD34 + Hematopoietic Progenitor Cells Where It Establishes Latency by Macropinocytosis

Abstract

Virion entry is targeted by antivirals and natural immunity to prevent infection. Natural preexisting immunity is ineffective at clearing an HCMV infection, and an incomplete understanding of the viral glycoproteins and cellular receptors that mediate entry has hampered inhibitor development. Nevertheless, HCMV entry remains a viable drug target. Our characterization here of HCMV entry into primary CD34 + hematopoietic progenitor cells through macropinocytosis and our comparison to viral entry into fibroblast cells highlight virion uncoating and tegument disassembly as a divergence point between productive and latent infections. Further definition of tegument disassembly may permit the development of interventions to inhibit this process to block productive infection or to trigger it in incompletely differentiated cells to prevent the seeding of the latent reservoirs that make HCMV infections incurable.