AAV (Adeno-associated virus) encodes four non-structural proteins, Rep78, Rep68, Rep52, and Rep40, which are involved in different stages of the viral life cycle. Rep78 and Rep68 primarily regulate viral DNA replication, gene expression, and integration, while Rep52 and Rep40 play a crucial role in virus assembly. 

Here’s a breakdown of their functions:

Rep78 and Rep68:

• Viral DNA Replication: These larger Rep proteins are essential for initiating and facilitating the replication of the AAV genome. 
• Regulation of Gene Expression: They can either activate or repress the expression of other AAV genes, influencing the overall viral life cycle. 
• Site-Specific Integration: Rep78 and Rep68 are involved in integrating the AAV genome into the host cell’s DNA, specifically at a particular locus on human chromosome 19, called AAVS1. 

Rep52 and Rep40:

• Virus Assembly: These smaller Rep proteins are crucial for packaging the newly synthesized viral DNA into newly formed capsids, essentially facilitating the assembly of new virus particles. 
• Helicase Activity: Both Rep52 and Rep40 possess helicase activity, which is important for unwinding DNA during replication and packaging. 

In essence, Rep78 and Rep68 handle the “command and control” aspects of the AAV lifecycle, while Rep52 and Rep40 handle the “construction crew” aspect.