Pandemic H1N1 mutation in India resembles Dutch findings

Mar 16, 2010 (CIDRAP News) – Researchers from India's National Institute of Virology (NIV) yesterday announced that they detected a small mutation in pandemic H1N1 virus in samples from three patients, fueling speculation that it may be the same change that surfaced in two Dutch patients last fall.

Experts say if the two mutations are the same it doesn't appear to have much clinical significance, though the development is worth monitoring, because the change could theoretically enhance viral replication and virulence.

Indian researchers said the throat swab samples from the patients show a small mutation in the polymerase 2 (PB2), gene, the Times of India reported today. Dr A.C. Mishra, the NIV's director, said the virus was not resistant to oseltamivir (Tamiflu).

Dr Michael Shaw, associate director of the US Center for Disease Control and Prevention (CDC) Laboratory Science Influenza Division, told CIDRAP News that he doesn't have any more details on the Indian findings aside from the Times of India story. However, he said the researchers' description sounds like the E627K mutation that was first reported by a group from the Netherlands at the end of September.

The Dutch researchers found the E627K mutation in the basic polymerase 2 (PB2) protein in samples from two patients who had links to an island in northern Holland. They described their findings in a Sep 28 report on ProMed mail, an Internet-based reporting system of the International Society for Infectious Diseases. One of the patients, an adult, had a mild infection, and the other, a girl, recovered after a week of treatment with oseltamivir.

The E627K mutation in PB2 had previously been linked to increased replication and possible virulence changes in other influenza A viruses. Though the mutation has been rarely seen in avian-derived viruses, it had been associated with fatal H5N1 cases and H7N7 infections in humans, the researchers said in their ProMed mail report.

They added that the clinical and epidemiological significance of the mutation is unclear and that experimental infection of ferrets with the H1N1 virus containing the mutation did not suggest increased shedding, virulence, or transmissibility.

Shaw said nothing stood out about the Dutch patients—the mutation didn't appear to give the virus a transmission advantage. If the mutation described by the Indian researchers turns out to be the E627K in PB2 mutation, "it's an interesting observation, but probably irrelevant clinically," he said.

Virologists expect to see such mutations and remain on the lookout for clusters of such cases, Shaw said. Scientists are concerned about the mutation, because it could allow the virus to better adjust to host body temperature. However, he added that reports of two or three patients at a time, such as the Indian and Dutch reports, aren't worrisome.

Mishra told the Times of India that, although the mutation they found has been linked to increased replication and virulence changes in other influenza A viruses, they did not detect any increased virulence or replication in the isolates they studied. "The mutation is not very significant in that sense," he said.

Dr Siddharth Dalvi, a consulting microbiologist and immunologist, told the Times that protein made by the PB2 gene doesn't directly play a role in immune response, so point mutations may have little clinical impact. However, he added that the mutation could theoretically change replication.

See also:

Mar 16 Times of India story

Sep 28, 2009, ProMed mail post

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