Identification of Cellular Proteins That Interact with the Adeno-Associated Virus Rep Protein

Adeno-Associated Virus Type 2 Modulates the Host DNA Damage Response Induced by Herpes Simplex Virus 1 during Coinfection

“…Replicating HSV-1 DNA contains stretches of singlestranded DNA (39) which may recruit RPA32 into HSV-1 RCs also independently of ICP8. Single-stranded DNA binding proteins such as RPA32 are proposed to stimulate AAV2 DNA replication (64,79), e.g., by protecting the single-stranded replication products from nucleases (63) and by enhancing the binding and nicking of Rep proteins at the replication origins (79).…”

“…Besides viral helper factors, the fate of AAV2 replication also depends on cellular proteins. Recently, cellular proteins have been identified that interact with AAV2 Rep78/68 in adenovirus (Ad)-or HSV-1-supported AAV2 replication (63,65). Of these, the largest functional categories correspond to cellular proteins which are involved in DNA metabolism, including DNA replication, repair, and chromatin modification.…”

“…During the course of infection, several small RCs rapidly expand and fuse to large structures, which displace the cellular chromatin and fill the entire cell nucleus (28,35,37,79,91). AAV2 RCs contain AAV2 proteins, as well as defined helper virus proteins and cellular proteins (3,35,63,65,75,79,90,91). Replicating AAV2 has inhibitory effects on both the host cell (9,41,68,71,73,74,100,101) and the helper virus (5,30,31,34,40,44,61,84,100).…”

The Role of DNA Repair Pathways in Adeno-Associated Virus Infection and Viral Genome Replication / Recombination / Integration

“…It appears that there would be many other Rep68/78-associated DNA repair pathways that have yet to be identified. This is because a recent study using a tandem affinity purification (TAP) approach has demonstrated physical interaction of Rep78 with many DNA repair-associated proteins including DNA-dependent protein kinase catalytic subunit (DNA-PKcs), minichromosome maintenance (MCM) proteins, Ku70/80, proliferating cell nuclear antigen (PCNA), RPA, and structural maintenance of chromosome 2 (SMC2) (Nash et al, 2009). …”

SiDNA and Other Tools for the Indirect Induction of DNA Damage Responses

“…The AAV genome, like that of Ad, consists of an ssDNA molecule with ITRs at both ends, resulting in the formation of double-hairpin structures (Brown, 2010). AAV infection requires helper functions, which may be supplied by Ad or other viruses (Geoffroy & Salvetti, 2005), and components of the host cell DNA replication machinery (Nash et al, 2009). Viral replication takes place in the nucleus, where cellular proteins, including RPA, colocalize with viral proteins in replication centers (Stracker et al, 2004).…”