H1N1 and H9N2 Offspring Can Be More Lethal

Today's talks about H1N1 and H9N2 offspring can be more lethal.

Mar 2, 2011 (CIDRAP News) – Chinese researchers who tested reassortants that combined the 2009 H1N1 virus with H9N2, a subtype that commonly circulates in birds, found that several were more pathogenic then the parent viruses, which they said could pose a pandemic threat.

Their experiments also found that of 127 reassortants between the two viruses, as many as 57.5% had a high ability to replicate, similar to the two parent viruses, which suggests that the two viruses have a high genetic compatibility. The findings appeared in the Proceedings of the National Academy of Sciences. The report was edited by Dr Peter Palese, a well-known virologist at Mount Sinai School of Medicine in New York City.

Though H9N2 is a low-pathogenic virus, it has also been found in pigs, which infectious disease experts have said could be a "mixing vessel" for animal and human flu viruses, producing novel flu viruses with pandemic potential.

Human infections with H9N2 have been reported, and the World Health Organization (WHO) includes the virus alongside H5N1 in its annual recommendations for pandemic flu vaccine candidate viruses.

Unpacking virulence differences
Using reverse genetics, the study group attempted to make all possible 127 reassortants from an avian H9N2 influenza virus and the 2009 H1N1 virus. Then they categorized each into one of four groups based on replication ability.

A total of 73 reassortants showed a high ability to replicate, and the group evaluated the pathogenicity of all of them in mice. Based on those findings, they sorted the viruses into three groups that varied by how sick the mice got. Eight of the reassortants caused more severe disease, based on clinical observation such as ruffled coat, lethargy, and dyspnea, and microscopic signs in lung tissue, which included interstitial pneumonia and bronchopneumonia, edema, hemorrhage, epithelial cell dropout, and infiltration of inflammatory cells.

All eight of the most pathogenic reassortants had the polymerase acid (PA) gene segment from the 2009 H1N1 virus, which the authors suggest is required for the emergence of the most virulent reassortants they tested. Further analysis showed that the basic polymerase 1 (PB1) gene of the 2009 H1N1 virus usually attenuated the pathogenicity of the reassortants, and the neuraminidase of that parent virus typically increased their virulence.

Projecting illness impacts
Though the more virulent reassortants were a major concern, the less pathogenic ones that emerged are also worth noting, the authors state, because they could circulate undetected in mammals, and mutation or further reassortment could also pose a pandemic threat.

Not all of the reassortants that had the PA gene segment from the 2009 H1N1 virus were more virulent that their parent viruses, which the investigators said suggests that other gene segments play a role in pathogenicity.

They said their examination of the sickest mice showed no evidence of systemic spread, but all viruses replicated efficiently in the lungs and showed high polymerase activity. "These results suggested that a high virus load and high polymerase activity were important factors for the virulence of the reassortants in mice," they wrote.

The group concluded that reassortants between H9N2 and pandemic H1N1 could pose a public health threat and that the PA gene segment findings in the most virulent ones could serve as a marker for identifying H9 reassortants that present the greatest risks.

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