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H5N1 in Indonesia

Recombinomics Commentary
October 7, 2004

Since the articles linked above seem to add to the confusion associated with the H5N1 pandemic in Asia, it is worth reviewing the data, which is quite clear cut, but poorly understood. 

Here is some background.  The sequences of H5N1 isolates from Indonesia were placed on deposit at GenBank on Jun 14, 2004 and were publicly available in mid July

The sequences, along with sequences from Vietnam, Thailand, Hong Kong, and several provinces in China, were discussed in a Nature paper, also published in July

The paper used re-assorted genes to place the isolates into broad genotypic groupings and most of the recent (2003 and 2004) isolates where classified as genotype Z.  This included the 2003 and 2004 isolates from Indonesia as noted in the Nature paper:

"All of the viruses that caused outbreaks in Indonesia, Thailand and Vietnam in late 2003 and early 2004 (refs 1, 9) were genotype Z viruses (Fig. 4)."

However, the genotype Z isolates could be further divided because they were all recombinants and had picked up regionally specific polymorphisms.  Thus, among H5N1 isolates, several of the polymorphisms were only found in isolates from Vietnam and Thailand (and some were only on Thailand while others were only in Vietnam).  There were other polymorphisms only found in the isolates from Indonesia and additional polymorphisms with a slightly broader distribution (as well as isolates with polymorphisms restricted to other geographical locations).

These regional specific polymorphisms were not restricted to a single gene.  In fact they were present in all 8 genes and frequently were clustered.  This distribution was due to recombination in cells infected with two distinct influenza A viruses.  In cells dually infected, recombination can occur in all 8 genes and there are many very clear cut examples, especially in the more recent isolates.  This is due to the fact that there are more available sequences from recent isolates and the frequency of productive dual infections is increasing as the influenza A reservoir becomes larger and more diverse, leading to extreme genetic instability.

Most of the polymorphisms restricted to Thailand and Vietnam are NOT new mutations.  An expanded search identifies almost all of the polymorphisms in other serotypes including a heavy concentration in serotypes normally associated with mammalian isolates.  The acquisition (via recombination) of these mammalian polymorphisms correlates with an expanded host range and fatal infections in humans.

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