A Virologist’s Perspective on Influenza A(H1N1)

Howard Hughes Medical Institute investigator Robert Lamb, a virologist and influenza expert at Northwestern University:-

1. Swine influenza, which is at the center of the 2009 outbreak, is a respiratory disease of pigs caused by type A influenza viruses that causes regular outbreaks in pigs. People do not normally get swine flu, but human infections can and do happen. Swine flu viruses have been reported to spread from person-to-person, but in the past, this transmission was limited and not sustained beyond three people.
2. The specific cause of the jump from one species to another remains something of a mystery, but many researchers believe it has to do with changes in the HA protein, which is responsible for recognizing receptors on the cells the virus infects.
3. We want to know how much cross-reactivity there is between the seasonal H1N1 and influenza A(H1N1). Cross-reactivity is the reaction against an antigen and an antibody that was directed against a similar but different antigen. “It may be that there’s a small amount of cross-reactivity that’s hard to measure, but that nonetheless gives you some protective effect and makes the difference between being very sick or mildly sick,” he said.
4. “Pigs have often been considered a potential halfway house for these viruses because they have receptors for both avian and human influenza.”Robert A. Lamb
5. From a genetic point of view, Lamb describes the virus as a “complicated reassortant, containing a mixture of genes from influenza viruses that infect Eurasian swine, American swine, birds and humans.”
6. Strains of flu virus differ from one another largely in the genes that code for surface molecules called glycoproteins, which are the primary targets of the body's immune system in defending against flu viruses.
7. H1N1 belongs to the H1 influenza A virus family, just 1 of 16 subtypes. Labeled H1 to H16, each subtype is named for the distinct structural biology of one of the key influenza surface proteins, hemagglutinin (HA). All H1 viruses, for instance, share a similarly shaped HA protein. Influenza viruses are further distinguished by the shapes of their neuraminidase (NA) proteins, of which there are nine subtypes.
8. The virus can undergo two types of structural changes:-

• Small changes in the virus’s coat proteins happen continually and result in new strains. This is a main reason why people can get the flu more than once and why they need to get a new flu vaccine every year. The virus coat can also change abruptly into a new subtype that has an HA protein or an HA-NA protein combination that has not been seen in humans, at least not for many years. Most people would have little or no innate protection against this new virus. And if the virus can spread easily from person to person, a pandemic may occur.

• Influenza viruses evolve constantly, and their physical structure is again the reason. Inside its spherical shell, the virus particle houses eight separate RNA segments—which encode genes for 11 proteins—and this kind of segmented genome is ripe for recombination. If two different influenza viruses infect the same cell, for instance, they can easily exchange gene segments—generating theoretically up to 256 different offspring. Scientists call this phenomenon a genetic "reassortment," and the hybrid viruses are “reassortants.”

Flu pandemics in 1918, 1957, and 1968 caused millions of deaths. Both strain H2N2 (the cause of the 1957 pandemic) and strain H3N2 (the 1968 pathogen) are believed to have arisen by the exchange of genes between avian and human flu viruses, possibly following dual infection in humans. The deadliest pandemic, in 1918, was different. It was the result of strain H1N1, thought to be derived wholly from an ancestor that originally infected birds.