Life Cycle of AAV Virus-From Infection To Regeneration

 AAV transduces cells through several stages: (1) viral binding to cell surface receptor/coreceptor, (2) endocytosis of the virus, (3) intracellular trafficking of the virus through the endosomal compartment, (4) endosomal escape of the virus, (5) intracellular trafficking of the virus to the nucleus and nuclear import, (6) virion uncoating, (7) viral genome conversion from a single-stranded to a double-stranded genome capable of expressing an encoded gene [34-36]. Since AAV can’t encode polymerases, AAV is dependent upon cellular polymerase activity to replicate its own genome [37]. The presence of a helper virus such as adenovirus is indispensable for wild-type AAV to facilitate gene expression and replication. (Figure 2A) Without helper virus, expression of Rep68/Rep78 would be restricted owing to Ying Yang 1 (YY1) repression of the P5 promoter, leading to inhibition of AAV genome replication and gene expression, and initiation of AAV chromosome integration (Figure 2B) [38]. AAV establishes latency by undergoing specifically integration into a genome site, termed as the adeno-associated virus integration site 1 (AAVS1), a 4kb region on chromosome 19 (q13.4).