Abstract
Canine distemper virus (CDV) becomes able to use human receptors through a single amino acid substitution in the H protein. In addition, CDV strains possessing an intact C protein replicate well in human epithelial H358 cells. The present study showed that CDV strain 007Lm, which was isolated from lymph node tissue of a dog with distemper, failed to replicate in H358 cells, although it possessed an intact C protein. Sequence analyses suggested that a cysteine-to-tyrosine substitution at position 267 of the V protein caused this growth defect. Analyses using H358 cells constitutively expressing the CDV V protein showed that the V protein with a cysteine, but not that with a tyrosine, at this position effectively blocked the interferon-stimulated signal transduction pathway, and supported virus replication of 007Lm in H358 cells. Thus, the V protein as well as the C protein appears to be functional and essential for CDV replication in human epithelial cells.
Highlights
The genus Morbillivirus in the family Paramyxoviridae consists of six members: measles virus (MV), rinderpest virus, phocine distemper virus, peste-des-petits-ruminants virus, cetacean morbillivirus, and canine distemper virus (CDV)
We demonstrated that wild-type CDV strains have the potential to replicate in human epithelial H358 cells by using hNectin4 as a receptor [30]
Vero.DogSLAMtag and Vero/human SLAM (hSLAM) cells [18,39] were maintained in DMEM supplemented with 5% fetal bovine serum (FBS) and 1 mg/ml geneticin. 007Lm-VDS was isolated from lymph node tissue obtained from a dog with distemper using Vero.DogSLAMtag cells [18] and passaged 5–10 times in these cells [38]. 007LmH358p8 was obtained as follows. 007Lm-VDS was inoculated into monolayers of H358 cells and passaged eight times in these cells
Summary
The genus Morbillivirus in the family Paramyxoviridae consists of six members: measles virus (MV), rinderpest virus, phocine distemper virus, peste-des-petits-ruminants virus, cetacean morbillivirus, and canine distemper virus (CDV). These viruses cause acute systemic infections in specific animal species [1]. A great number of nonhuman primates have been lethally infected by CDV in the last several years [11,12,13]. It is of concern whether CDV possesses or can acquire the ability to infect humans
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