Generation of diversity in retroviruses

Abstract

Retroviruses are unique in that their propagation includes transfer of genetic information from RNA to DNA. Two enzymes (RT and RNA polymerase II) that participate in their replication process do not encode editing functions and are thus "error prone." Current estimates indicate that up to one nucleotide substitution per genome occurs per retrovirus replication cycle. In addition, rearrangements can occur during reverse transcription. These mutations result in viral populations in which the wild-type sequence can only be defined by consensus. Retroviruses are also unusual among viruses in their high recombination frequency, which is the result of the copackaging, and then reverse transcribing of two different RNA genomes in the same particle. Recombinants are formed during copying of RNA templates into DNA. With the ability to mutate and recombine genetic information at a higher rate, retroviral populations are poised to respond to selective forces, which may increase or decrease replication of particular genotypes. Interspecies transmission of retroviruses or retroviral genes also likely plays a role in generating diversity. Endogenous proviruses exist in the germline of many vertebrates; pedigrees indicate that recent infections of the germline have also occurred. Thus, the selective forces that mold the retroviral genome may be opposing: selection for efficient replication as exogenous viruses versus selection for passive replication as endogenous proviruses. The latter may be more advantageous over the course of evolution since the survival of the retrovirus is ensured by survival of the host organism. Segments of endogenous viruses may reappear in exogenous viruses through recombination and thus these endogenous sequences are perpetuated.