Anellovirus protein encoded by ORF2/3 functions as the viral replication initiation protein

What is it about?

Anelloviruses are a family of very common small DNA viruses that are part of the healthy human virome. Despite their ubiquity, how they replicate inside human cells was not well understood. This study found that a previously mysterious viral protein, encoded by a part of the viral genome called ORF2/3, is able to start the process by which the virus copies its DNA. The researchers showed that this ORF2/3 protein, which they named Replication initiation protein, or Rip, alone can trigger DNA replication. They also identified the position in the viral genome that is the starting point of DNA replication (known as the replication origin) and showed that Rip interacts with human cell machinery responsible for copying DNA. This work gives the first picture of how anelloviruses exploit human enzymes to make more copies of themselves.

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Photo by MJH SHIKDER on Unsplash

Photo by MJH SHIKDER on Unsplash

Why is it important?

Anelloviruses are among the most widespread viruses in humans, yet scientists have known almost nothing about how they function. This work fills a major gap in our knowledge of these viruses and opens the door to future research on how these viruses persist in people without causing obvious disease. Because levels of anelloviruses in the blood are being used as indicators of immune system health, and have been linked to immune suppression and organ transplant outcomes, clarifying how anelloviruses replicate provides important context for interpreting these levels in both medical and research settings and for understanding their relationship to immune health.

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