A new strategy of immune evasion by influenza A virus: Inhibition of monocyte differentiation into dendritic cells

Dendritic cells (DC) play a versatile role in orchestrating immune responses against influenza virus. During inflammation or infection, monocytes preferentially differentiate to generate DCs. Here, we demonstrate that in vitro infection of monocytes with influenza virus impairs their development into DCs. Influenza infection of monocytes, pre-treated with GM-CSF and IL-4 for DC differentiation, was minimally productive and non-cytopathic. In spite of successful viral genome transcription, viral protein synthesis was restricted at an early stage. However, despite the limited replication, influenza infected monocytes failed to develop distinctive DC-like morphologies. Infected cells expressed reduced amounts of CD11c, CD172a, CD1w2 and CCR5. Antigen endocytosis by infected monocytes was also affected. Cytokine expression profiles were also modified which was conducive for arresting DC differentiation. At least limited viral replication was necessary for complete inhibition of differentiation. This identifies a new strategy by influenza virus to interfere with DC differentiation and evade virus specific immune responses.