Abstract
Only a handful of cell types, including fibroblasts, epithelial, and endothelial cells, can support human cytomegalovirus (CMV) replication in vitro, in striking contrast to the situation in vivo. While the susceptibility of epithelial and endothelial cells to CMV infection is strongly modulated by their anatomical site of origin, multiple CMV strains have been successfully isolated and propagated on fibroblasts derived from different organs. As oral mucosal cells are likely involved in CMV acquisition, we sought to evaluate the ability of infant labial fibroblasts to support CMV replication, compared to that of commonly used foreskin and fetal lung fibroblasts. No differences were found in the proportion of cells initiating infection, or in the amounts of viral progeny produced after exposure to the fibroblast-adapted CMV strain AD169 or to the endothelial cell-adapted strain TB40/E. Syncytia formation was, however, significantly enhanced in infected labial and lung fibroblasts compared to foreskin-derived cells, and did not occur after infection with AD169. Together, these data indicate that fibroblast populations derived from different tissues are uniformly permissive to CMV infection but retain phenotypic differences of potential importance for infection-induced cell–cell fusion, and ensuing viral spread and pathogenesis in different organs.
Highlights
Horizontal transmission of human cytomegalovirus (CMV) is thought to occur by contact between contaminated bodily fluids such as urine and saliva and the epithelial layers of oronasal mucosae
We show that infant labial fibroblasts (LFs) are as permissive to CMV infection as foreskin fibroblasts (FFs) and MRC-5 fetal lung fibroblasts (MRs), indicating that oral fibroblasts may contribute to CMV acquisition and/or spread
A population of oral mucosal cells derived from the labial tissues of a three-monthold infant (Figure 1A) was cultured in CnT-PR medium, which supported the growth of epithelial cells until passage four, when the first cells with fibroblast-like morphology appeared
Summary
Horizontal transmission of human cytomegalovirus (CMV) is thought to occur by contact between contaminated bodily fluids such as urine and saliva and the epithelial layers of oronasal mucosae. Ciliated respiratory epithelial cells were recently reported to be permissive to infection, but the number of antigen-positive cells detected in nasal turbinates was low and viral yields were limited, suggesting that these cells might not be major ports of entry [31]. Either small numbers of initially infected nasal or oral epithelial cells are sufficient to mediate transmission, as suggested by some modeling efforts [32], or the routes whereby CMV is acquired during primary infection have not yet been found
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