Super resolution microscopy reveals that Caveolin-1 is required for antiviral immune response (110.8)

Abstract

Caveolae are integral to numerous signaling pathways but their function in antiviral signaling is largely unexplored. Understanding spatial distribution and dynamics of receptors within unperturbed membranes is essential for elucidating their role in antiviral signaling, but conventional studies of detergent-resistant membrane fractions cannot provide this information. While it is known that viruses exploit caveolae for entry into host cells, this study instead demonstrates an entry-independent mechanism for virus evasion of host cell defenses through disruption of clusters of signaling molecules organized within caveolae. Super-resolution microscopy has enabled the first single-molecule imaging of interactions between type I interferon receptors (IFN-R) and caveolae. In particular, cav-1b knockdown caused IFN-R clusters to disperse, suppressing antiviral immune response through abrogation of downstream signaling, a response strongly suggesting that IFN-R organization within caveolae is critical for IFN-mediated antiviral defense.