Dynamics of Human Cytomegalovirus Infection in CD34+ Hematopoietic Cells and Derived Langerhans-Type Dendritic Cells

Roxanne Coronel, Sachiko Takayama, Timothy Juwono, Laura Hertel

Acquisition of human cytomegalovirus (CMV) usually occurs by contact between contaminated bodily fluids, such as urine and saliva, and host mucosal cells. Langerhans-type dendritic cells (LC) are the only type of immune cells found in the outermost layers of the oral mucosae, where they not only provide a first line of defense against CMV, but can easily be targeted by orally administered vaccines, while their bone marrow resident progenitors are important sites of virus latency. In this work, we tracked the progress of infection in CD34(+) progenitor cells, immature and mature LC (iLC and mLC) exposed to the clinical-like strain TB40-BAC4, or to the vaccine strain AD169varATCC, prior to their long-term maintenance in either immature or mature conditions. We show that the genomes of both strains are efficiently maintained in CD34(+) cells during their differentiation into iLC, although this requires the presence of higher amounts of input AD169varATCC DNA. Lipopolysaccharide and CD40 ligand induced maturation of iLC derived from latently infected progenitors was not associated with robust viral genome replication and progeny production, while maturation of directly infected iLC increased and prolonged expression of the viral immediate-early proteins. While effective replication of viral genomes from both strains occurred only in mLC, both iLC and mLC produced viral progeny, suggesting that both types of LC may contribute to CMV horizontal transmission in vivo.