BackgroundIt is known that crustaceans and insects can persistently carry one or more viral pathogens at low levels, without signs of disease. They may transmit them to their offspring or to naïve individuals, often with lethal consequences. The underlying molecular mechanisms have not been elucidated, but the process has been called viral accommodation. Since tolerance to one virus does not confer tolerance to another, tolerance is pathogen-specific, so the requirement for a specific pathogen response mechanism (memory) was included in the original viral accommodation concept. Later, it was hypothesized that specific responses were based on the presence of viruses in persistent infections. However, recent developments suggest that specific responses may be based on viral sequences inserted into the host genome.Presentation of the hypothesisNon-retroviral fragments of both RNA and DNA viruses have been found in insect and crustacean genomes. In addition, reverse-transcriptase (RT) and integrase (IN) sequences are also common in their genomes. It is hypothesized that shrimp and other arthropods use these RT to recognize "foreign" mRNA of both RNA and DNA viruses and use the integrases (IN) to randomly insert short cDNA sequences into their genomes. By chance, some of these sequences result in production of immunospecific RNA (imRNA) capable of stimulating RNAi that suppresses viral propagation. Individuals with protective inserts would pass these on to the next generation, together with similar protective inserts for other viruses that could be amalgamated rapidly in individual offspring by random assortment of chromosomes. The most successful individuals would be environmentally selected from billions of offspring.ConclusionThis hypothesis for immunity based on an imRNA generation mechanism fits with the general principle of invertebrate immunity based on a non-host, "pattern recognition" process. If proven correct, understanding the process would allow directed preparation of vaccines for selection of crustacean and insect lines applicable in commercial production species (e.g., shrimp and bees) or in control of insect-borne diseases. Arising from a natural host mechanism, the resulting animals would not be artificially, genetically modified (GMO).ReviewersThis article was reviewed by Akria Shibuya, Eugene V. Koonin and L. Aravind.