Increased replication of respiratory syncytial virus in the presence of cytokeratin 8 and 18

Shirato, Kazuya; Ujike, Makoto; Kawase, Miyuki; Matsuyama, Shutoku

Previously, it was reported that productive viral infection, viral protein synthesis, and viral RNA replication of respiratory syncytial virus (RSV) operated efficiently in two human epithelial cell lines (HEp‐2 and A549), but not in a human mast‐cell line, HMC‐1. Based on these observations, it was hypothesized that HMC‐1 cells lack the machinery required for RSV replication. To identify the host factors required for RSV replication, cDNA subtraction using A549, HEp‐2, and HMC‐1 cells was performed, and cytokeratin 18 (C18) was identified as a candidate host factor. Because C18 is generally expressed in simple epithelia with cytokeratin 8 (C8), HMC‐1 cells that constitutively express C18 and C8 (HMC‐1‐C8/18) were established to evaluate the role of C8/18 in RSV replication. In HMC‐1‐C8/18 cells, RSV RNA replication was increased, and the amount of infective virus produced was also increased in the cellular fraction after RSV spinoculation, whereas RSV production was decreased in A549 cells in which C18 expression was knocked down. These data suggest that the replication of RSV increases in the presence of C8/18. J. Med. Virol. 84:365–370, 2012. © 2011 Wiley Periodicals, Inc.