Evidence that Receptor Destruction by the Sendai Virus Hemagglutinin-Neuraminidase Protein Is Responsible for Homologous Interference

Receptor destruction has been considered one of the mechanisms of homologous Sendai virus (SeV) interference. However, direct evidence of receptor destruction upon virus infection and its relevance to interference is missing. To investigate a precise mechanism of homologous interference, we established SeV persistently infected cells. The persistently infected cells inhibited superinfection by homologous SeV but supported replication of human parainfluenza virus 2 (hPIV2) and influenza A virus (IAV). We confirmed that SeV particles could not attach to or penetrate the infected cells and that the hemagglutinin-neuraminidase (HN) protein of SeV was involved in the interference. Lectin blot assays showed that the alpha 2,3-linked sialic acids were specifically reduced in the SeV-infected cells, but the level of alpha 2,6-linked sialic acids had not changed. As infection with IAV removed both alpha 2,3- and alpha 2,6-linked sialic acids, especially alpha 2,3-linked sialic acids, IAV-infected cells inhibited superinfection of SeV. These results provide concrete evidence that destruction of the specific SeV receptor, alpha 2,3-linked sialic acids, is relevant to homologous interference by SeV. IMPORTANCE Viral interference is a classically observed phenomenon, but the precise mechanism is not clear. Using SeV interference, we provide concrete evidence that reduction of the alpha 2,3-linked sialic acid receptor by the HN of SeV is closely related with viral interference. Since SeV infection resulted in decrease of only alpha 2,3-linked sialic acids, IAV, which also utilized alpha 2,6-linked sialic acids to initiate infection, superinfected the SeV-infected cells. In contrast, SeV could not superinfect the IAV-infected cells because both alpha 2,3- and alpha 2,6-linked sialic acids were removed. These results indicate that receptor destruction critically contributes to viral interference.