Retroviral RNA Dimerization and Packaging

The fact that all other viruses encapsidate single copy genomes begs the question of why retroviruses co-package two genomics RNSa (gRNAs). One reason may be economy of scale: RNA dimerization allows formation of a unique structure – the dimer linkage – that distinguishes gRNAs from mRNAs. Monomeric HIV-1 RNAs are packaged when engineered with tandem dimer linkages, underscoring the importance of this RNA structure, and not gRNA counting per se, to packaging.

Co-packaging gRNAs allows retroviruses to generate intact proviruses despite pervasive gRNA nicking. Template switching during reverse transcription is probably why retroviruses maintain infectivity when their gRNAs are damaged by gamma rays, and why retroviruses are much less radiation-sensitive than RNA viruses like vescicular stomatitis virus. Researchers previously thought retroviral recombination might be mutagenic, but these notions have been dispelled. HIV-1 particles with two gRNAs generate full-length proviruses more efficiently than virions engineered to contain single gRNAs. Thus, another advantage of gRNA dimers appears to be increased replication fidelity.

Retroviral RNA Dimerization and Packaging

Co-packaging gRNAs promotes higher recombination frequencies for retroviruses than all other viruses, allowing rapid loss of deleterious alleles and re-assortment of genome segments. With approximately three to ten crossovers occurring during the synthesis of every provirus, recombination is perhaps 10-fold more frequent than reverse transcriptase base substitution rates, and is an evolutionary driving force for retroviruses such as HIV-1 that display high levels of replication and multi-strain infection.

These observations help seal the case for likely evolutionary advantages of dimeric genome packaging. The DLS in its immature form, which results only upon association of two gRNAs, likely provides the means for selective gRNA packaging. The need to generate an intact provirus provides a strong motive for packaging redundant genetic information. And because retroviruses encapsidate gRNA dimers, recombination can provide the opportunity for almost limitless combinatorial genetic sampling.

Retroviral RNA Dimerization and Packaging: The What, How, When, Where, and Why. (2010) PLoS Pathog 6(10): e1001007. doi:10.1371/journal.ppat.1001007


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