Defective interfering particle

In virology, defective interfering particles (DIPs), also known as defective interfering viruses, are spontaneously generated virus mutants in which a critical portion of the particle's genome has been lost due to defective replication. DIPs are derived from and associated with their parent virus, and particles are classed as DIPs if they are rendered non-infectious due to at least one essential gene of the virus being lost or severely damaged as a result of the defection. A DIP can usually still penetrate host cells, but requires another fully functional virus particle (the 'helper' virus) to co-infect a cell with it, in order to provide the lost factors. The existence of DIPs has been known about for decades, and they can occur within nearly every class of both DNA and RNA viruses.

DIPs are a naturally occurring phenomenon that can also be synthesized for experimental use. They are spontaneously produced by error-prone viral replication, something particularly prevalent in RNA viruses over DNA viruses due to the enzyme used (replicase, or RNA-dependent RNA polymerase.) DI genomes typically retain the termini sequences needed for recognition by viral polymerases, and sequences for packaging of their genome into new particles, but little else. The size of the genomic deletion event can vary greatly, with one such example in a DIP derived from rabies virus exhibiting a 6.1 kb deletion. In another example, the size of several DI-DNA plant virus genomes varied from one tenth of the size of the original genome to one half.

The particles are considered interfering when they affect the function of the parent virus through competitive inhibition during coinfection. In other words, defective and non-defective viruses replicate simultaneously, but when defective particles increase, the amount of replicated non-defective virus is decreased. The extent of interference depends on the type and size of defection in the genome; large deletions of genomic data allow rapid replication of the defective genome. During the coinfection of a host cell, a critical ratio will eventually be reached in which more viral factors are being used to produce the non-infectious DIPs than infectious particles.

This interfering nature is becoming more and more important for future research on virus therapies. It is thought that because of their specificity, DIPs will be targeted to sites of infection. In one example, scientists have used DIPs to create "protecting viruses", which attenuated the pathogenicity of an influenza A infection in mice to a point that it was no longer lethal.

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