腺病毒是常见的病原微生物。目前，已发现57种血清型人类腺病毒。在5型腺病毒的生活周期中，纤毛蛋白过量表达并且先于子代病毒从宿主细胞中释放出来。过量的纤毛蛋白会结合周围细胞表面的受体，从而抑制了子代腺病毒对细胞的感染。另外，部分血清型腺病毒的受体为各种细胞连接分子，腺病毒与受体结合可破坏细胞间连接，促进子代病毒的传播，进而感染远处的细胞。由于不同的腺病毒所识别的受体不同，并且纤毛与受体的亲和力也存在差异，腺病毒感染细胞所呈现的感染方式是不一样。本课题研究显示，5型腺病毒（Ad5）与3型、35型（Ad3、Ad35）相比，感染的方式更加分散。将Ad5的纤毛的柄（shaft）和头部（knob）区域更换成Ad35的纤毛shaft和knob区域而构建成的嵌合型病毒Ad5F35，它的感染方式与Ad5不同，但与Ad35的感染方式相近。Ad5F35和Ad5F35K++两种病毒识别相同的受体，但是与受体的亲和力不同，Ad5F35K++具有更高的亲和力。Ad5F35和Ad5F35K++两种病毒的感染效率的比较表明，具有较高纤毛-受体亲和力的病毒在多轮感染中表现出相对低的感染效率。本论文的研究结果可能为过表达的纤毛蛋白的功能给予更多的解释，过量的纤毛蛋白可能与腺病毒的毒性之间存在一定的联系。另外，纤毛蛋白与受体亲和力对子代病毒传播影响对溶瘤腺病毒的进一步改造具有重要的指导意义。

Adenovirus (Ad) is a common pathogenic microorganism. Currently, 57 human Ad serotypes have been identified. Fiber protein is overproduced and released prior to progeny adenovirus during the life cycle of certain adenoviruses such as Ad5. The excessively released fiber molecules can mask receptors on the bystander cells, limiting the infection capacity of progeny adenoviruses. Additionally, receptors for group C and certain group B Ad are the components of intercellular junction. When adenoviruses attach to their receptors, the intercellular junction will be disrupted, which may enhance the spread of progeny viruses and thereby facilitate viral infection. As fiber molecules from different Ad specifically bind to different cellular receptors and the fiber-receptor affinity is different, the pattern of Ad infection and its spread may vary. In this study, we show that Ad5 infection can spread more efficiently compared to the infection of Ad3 and Ad35. The chimeric adenovirus Ad5F35 vector, which was engineered by exchanging the knob and shaft domains of Ad5 fiber with those of Ad35, showed an infection pattern similar to Ad35 instead of Ad5. The infection efficiency was also compared between Ad5F35 and Ad5F35K++ vector. The Ad5F35K++ vector possesses higher fiber-receptor affinity than Ad5F35. The results show that higher affinity will lead to lower infection efficiency in the multi-round viral infection. Our findings suggest that fiber overproduction may be related to the virulence of adenovirus. The effect of fiber-receptor affinity on adenoviral spreading may provide more guides for the reconstruction of oncolytic Ad and to clarify the mechanisms of Ad pathogenesis.