tailieunhanh - Báo cáo y học: " Integrin αvβ5 is a primary receptor for adenovirus in CAR-negative cells"

Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành y học dành cho các bạn tham khảo đề tài: Integrin αvβ5 is a primary receptor for adenovirus in CAR-negative cellsb | Lyle and McCormick Virology Journal 2010 7 148 http content 7 1 148 VIROLOGY JOURNAL RESEARCH Open Access Integrin av 5 is a primary receptor for adenovirus in CAR-negative cells Cynthia Lyle and Frank McCormick Abstract Background Viruses bind to specific cellular receptors in order to infect their hosts. The specific receptors a virus uses are important factors in determining host range cellular tropism and pathogenesis. For adenovirus the existing model of entry requires two receptor interactions. First the viral fiber protein binds Coxsackie and Adenovirus Receptor CAR its primary cellular receptor which docks the virus to the cell surface. Next viral penton base engages cellular integrins coreceptors thought to be required exclusively for internalization and not contributing to binding. However a number of studies reporting data which conflicts with this simple model have been published. These observations have led us to question the proposed two-step model for adenovirus infection. Results In this study we report that cells which express little to no CAR can be efficiently transduced by adenovirus. Using competition experiments between whole virus and soluble viral fiber protein or integrin blocking peptides we show virus binding is not dependent on fiber binding to cells but rather on penton base binding cellular integrins. Further we find that binding to low CAR expressing cells is inhibited specifically by a blocking antibody to integrin avP5 demonstrating that in these cells integrin avP5 and not CAR is required for adenovirus attachment. The binding mediated by integrin avP5 is extremely high affinity in the picomolar range. Conclusions Our data further challenges the model of adenovirus infection in which binding to primary receptor CAR is required in order for subsequent interactions between adenovirus and integrins to initiate viral entry. In low CAR cells binding occurs through integrin avP5 a receptor previously thought to be used