Human adenovirus type 7 (HAdV-7) is a clinically important pathogen associated with severe respiratory infections, yet its cellular entry mechanism has remained incompletely defined. Most existing studies have focused on individual receptor functions, leaving critical knowledge gaps unresolved. It remains unclear whether HAdV-7 relies on both CD46 and desmoglein-2 (DSG2), whether these receptors act synergistically or independently, and how their interactions influence viral infection dynamics. This study provides comprehensive evidence that HAdV-7 utilizes CD46 and DSG2 as synergistic co-receptors to mediate efficient infection, viral replication, and inflammatory pathology. This study resolves long-standing controversies regarding receptor usage in HAdV-7, elucidates a novel dual-receptor mechanism of infection, and offers a foundation for the design of novel adenovirus vectors with optimized tissue tropism.
Ye et al. (2026) studied this question.