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November 15, 2007
The influenza viruses are negative-strand RNA viruses, and, as such, lack the ability to interact by intermolecular recombination.
The above comments on negative strand influenza RNA is not consistent with the recent publication on recombination in Ebola. These data were presented in an ahead of the press publication entitled, “Isolates of Zaire ebolavirus from wild apes reveal genetic lineage and recombinants.”
The authors presented the sequences of two genes from ebola isolates. One gene the envelope glycoprotein, GP, was related to one of two lineages of Ebola. However, when a second gene, the NP nucleoprotein gene, was analyzed, it was found to be most closely related to the other lineage. Since ebola has a non-segmented genome, the relation of the two genes to the two distinct lineages signaled recombination.
Recombination is also frequently found in influenza, another negative sense RNA virus. However, since influenza is a segmented genome that can shuffle gene segments via reassortment, recombination requires that intragene switches of parental origin are required to demonstrate recombination.
However, this more stringent requirement has been met by multiple sequences generated by multiple genes sequenced by multiple labs. Demonstrations have been presented for H5N1 in PB2, PB1, PA, and NP. Clear examples are also seen in H1 swine isolates including PB2 and PA. These example involve large portions of the gene coming from one parental source, and other portions from a second parental source.
The recombination requires that the same host is infected with two or more species. One species provides a template for a portion of the gene, while a second species acts as a template for other portion(s) of the gene. Since all replicating genes must copy one strand using traditional base paring, the sense of the RNA, is not relevant. Negative sense RNA virus must make a positive sense copy, while positive sense RNA viruses must make a negative sense copy.
Recombination in positive sense RNA virsuses, such as coronaviruses, has been widely accepted, while examples of recombination in negative sense viruses have been discounted. The Ebola example is the first published under peer review. The number of examples is limited by a small sequence database.
In contrast, the sequence database for influenza is much larger and there are many more examples, although acceptance has been blunted by those focused on reassortment and random mutations. However, as the number of sequences grows, the role of de novo random mutations has become suspect.
Dual infections are most common between closely related sequences, because these sequences are found in hosts that have frequent contact. Dramatic examples of the shuffling of single nucleotide polymorphisms have been identified in H5N1 clade 2.2 isolates. One marker, NA G743A, was appended onto multiple clade 2.2 backbones this year. Similarly, the aggregation of diverse single nucleotide polymorphism into a single human H5N1 gene has also been described.
The demonstration of homologous recombination in the negative sense Ebola genome should accelerate the acceptance of similar examples in other negative sense genomes, including influenza.
Recombinomics Paper at Nature Precedings