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For most serotypes, adenovirus infection is mediated by the high-affinity binding of the fiber-knob region to a receptor of target cell, named as the coxsackie-Ad receptor (CAR) [17]. Upon attachment, interaction between the penton-base Arg-Gly-Asp (RGD) and cellular αv integrins, which can stimulate actin polymerization, leads to internalization of the virus into the endosome. Then the endosome acidifies, resulting in disassociation of capsid proteins and transportation of viral DNA into nucleus. Without integration into host genome, adenovirus genome remains in an episomal state, which guarantees the low risk of mutation (Figure 2). Life cycle of adenovirus is separated by DNA replication process into two distinct phases: the early and late, occurring before and after viral DNA replication, respectively. After the synthesis of viral genome and capsid, they are assembled into viral products, releasing out of cell, and the infected cell starts lysis [18].

To prevent infected cell lysis, recombinant replication deficiency virus has been developed as a gene delivery tool to replace wild-type adenovirus (Figure 1B). Once packaged into a E1-complementing cell line, which provides the E1 products in trans, such as QBI 293A Cells, recombinant viral will be easily propagated.

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Figure 2. Infection process of adenovirus. CAR receptor-fiber-knob adenovirus interaction and internalization process [19].



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