Heparin-sensitive receptor (on dendritic cells and monocytes)

The heparin-sensitive receptor is a cell surface molecule found on dendritic cells and monocytes that plays a critical role in the tropism and immunogenicity of adenovirus type 5 (Ad5) vectors. It specifically interacts with the KKTK motif located in the fiber shaft of the Ad5 capsid, a binding event that is inhibited by heparin but not by heparan sulfate. This interaction is a primary driver of the potent adaptive immune responses elicited by Ad5-based vaccines, but it is also responsible for the characteristic pyrogenic (fever-inducing) side effects and systemic toxicity associated with high-dose administration. Consequently, this receptor is a major focus in the design of next-generation viral vectors, where the fiber shaft is often modified or replaced to improve the safety profile while maintaining therapeutic efficacy.

Other names

Ad5 fiber shaft receptorKKTK-binding receptorHeparin-like receptor

The KKTK motif in the adenovirus type 5 (Ad5) fiber shaft binds to the heparin-sensitive receptor on dendritic cells and monocytes, facilitating viral entry and triggering innate immune signaling pathways that lead to adaptive immunity and pyrogenic responses.