Novel Forms Of Viral Genome Integrations

The transfer of genetic material between separate evolutionary lineages (horizontal transfer) is a recognized event that occurs between viruses as well as from DNA viruses and retroviruses to eukaryotic cells. Somatic integrations of viruses have been linked to persistent viral infection and genotoxic effects.

Integrations in germline cells can be transmitted vertically. The persistence and the outcome of these integrations in the host populations depend on their effects on the host fitness. If deleterious, integrations are lost. If they occur in chromosomal locations that are not transcribed or lack regulative functions, integrations may persist and accumulate mutations.

There also are examples of viral integrations being co-opted by the host and exerting beneficial functions. Because non-retroviral RNA viruses lack the coding for reverse transcriptase and the integration machinery needed for successful transfer to DNA genomes, their integration potentials were considered minimal. However, the number of studies showing genome integrations into both somatic and germline host cells from non-retroviral RNA viruses is increasing.

The first comprehensive description of a genome-integrated sequence from a nonretroviral RNA virus occurred in 2004 when four sequences with similarities to the insect flavivirus Cell Fusing Agent (CFA) were found to be integrated into the genome of Aedes spp. mosquitoes. Since then, nonretroviral integrated RNA virus sequences (NIRVS) have been identified in organisms as different as fungi, plants, invertebrates, and vertebrates.

In Drosophila melanogaster, chimeric DNA molecules formed between an infecting non-retroviral RNA virus and retrotransposons are made at the beginning of the infection and interact with the RNAi machinery to establish persistent infection. This process was also recently seen occurring in the main arboviral vector, the mosquito Aedes aegypti.

Whether NIRVS are the secondary products of this process (they are “mistakenly” integrated into the genome because they form chimeras with long-terminal repeat retrotransposons) or its primary components (continued transcription from NIRVS could help establish persistent infection) is unclear. Additionally, NIRVS have been associated with “integration-based immunity”, a form of acquired immunity to respective viruses. Details of this phenomenon are unknown. For instance, are NIRVS derived from specific regions of the viral genome or not? Do NIRVS have a length range? What is the degree of sequence specificity for “integration-based immunity” to occur? Does vertical transmission of NIRVS implicate acquired immunity in the progeny?

Answering all these biological questions is quite crucial for different reasons. First, NIRVS were identified in vectors for arboviruses, as a consequence NIRVS immunological properties could affect vector competence and have epidemiological consequences. Second, several nonretroviral RNA viruses are being employed as delivery agents for drugs and vaccines. It is important to understand which viral species and under which circumstances host genome integrations from nonretroviral RNA viruses occur for the safe application of these viruses in medicine.

These findings are described in the article entitled Nonretroviral integrated RNA viruses in arthropod vectors: an occasional event or something more? recently published in the journal Current Opinion in Insect Science. This work was conducted by Ken E. Olson from Colorado State University and Mariangela Bonizzoni from the University of Pavia.