Yan Li. Credit: Government of Canada

On 17 April, Canada's National Microbiology Laboratory in Winnipeg, Manitoba, was called in to help diagnose a cluster of cases of serious respiratory illness of unknown cause in Mexico. This was molecular virologist Yan Li's forte; his team was the first to identify and report the SARS coronavirus in Canada during the 2003 outbreak. Hannah Hoag talks to Li and to the laboratory's scientific director Frank Plummer about being the first to identify the Mexican virus as influenza, and about the laboratory's research into swine flu.

When you were first told about the disease outbreak in Mexico, what did you think you might be dealing with? Were you concerned that it might be another SARS?

Yan Li: Initially, it seemed that it wasn't influenza. The Mexicans were testing for it and not finding it. We thought that it might be another new pathogen, or even SARS. We are prepared to detect every possible respiratory pathogen, including influenza. First, we confirmed it was influenza using molecular diagnostic tests. But if it hadn't been, we could have tested for more than 20 other respiratory pathogens.

Frank Plummer: Our unknown pathogen protocol uses genetics, culture, microscopy and metagenomic approaches. But Yan's PCR, which targets the highly conserved matrix gene of the influenza virus, came up positive very quickly. By then we knew about the issue in the United States, and the matrix gene sequence was similar to what was being reported in California.

At what point did you realize that you were dealing with an influenza virus with pandemic potential?

Li: We had 51 samples, and 17 were positive for influenza A. I think that was when we started to worry. We've been talking about pandemic planning for years. We have been preparing laboratories for diagnosis and to identify any unknown or novel pandemic strains. It's our job. In this case, we initially thought it was an unknown respiratory pathogen, but then the samples were positive for influenza. We were excited, and we also felt that our work had paid off — we were prepared. We had been working for 10 years to be prepared. In the flu lab we had about 14 people including myself working around the clock.

Plummer: There was some dread too. We had been through this with SARS and that was exhausting. You're excited, but you have to be careful what you wish for.

Do you believe the World Health Organization acted appropriately in declaring pandemic phase 6 when it did?

Plummer: I think they did it appropriately. It probably met the technical definition of a pandemic sometime before. There is debate about whether severity needs to be included or not.

What additional influenza research is the laboratory doing now?

Plummer: One of the key questions here is the severity. Can the virus or host genetics account for that? We're genotyping the virus, looking for polymorphisms and correlating the genome sequences with the clinical outcomes. There's nothing new to report yet. Getting the data from Mexico has been a challenge because it is spread around different databases, but we'll get there. We're also starting to do some studies on the more severe cases we're seeing in Manitoba now [including those in First Nations communities].

Li: We are also performing animal studies to look at the pathogenicity of the virus. With time, we are closely monitoring antiviral susceptibility and the antigenic/genetic changes of the novel viral isolates,

One worry is that the virus will pick up genes from other influenzas and become more resistant to drugs or develop other dangerous features. Have you seen signs of reassortment with seasonal influenza or H5N1?

Li: Nothing yet. [The National Microbiology Laboratory receives about 10% of the isolates — the unusual ones — tested in Canada's provincial laboratories.] We are looking for antiviral resistance using genetic analysis, the most important assay to pick up any new mutations.