Visits: 379
It seems that after years of stability, the North American swine flu virus has jumped onto an evolutionary fast track, emerging out variants every year. Changes in animal husbandry specially increased rate of vaccination, may be spurring this evolutionary surge. Researchers say that dramatically different swine flu viruses could spell danger as is transmissible among humans. Because people have no immunity to many viruses from other species, strains that on rare occasions cross the species barrier can have deadly consequences. And pigs are considered as the mixing vessels in which swine, avian, and human influenza viruses mix and match.
Scientists believe, for example, that the last two flu pandemics, or worldwide epidemics, in 1957 and 1968, occurred when avian flu and human flu viruses swapped genes in pigs, creating a new hybrid virus that then spread to the humans. Most genetic changes in the flu viruses— human, pig, and bird—are small and subtle point mutations in the virus’s RNA. Less common but more alarming are sudden, wholesale changes that replace entire genes and are more likely to circumvent the immune system. This process, called genetic shift, is exactly what is now occurring in North American pigs. Thus, the latest swine influenza virus is a curious hybrid: The genes that code for its coat proteins derive from classical swine influenza, but half of its internal genes have been snatched whole from avian and human viruses. The structure of the influenza virus lends itself to such radical changes. The virus is made of eight single-stranded segments of RNA that together code for 10 proteins (see illustration). If two or more different viruses infect the same host cell, they can swap segments, creating new viral types. Most commonly, the virus swaps genes that code for its two surface proteins: hemagaglutinin (HA) and neuraminidase (NA). Both proteins spike off the virus’s outer coat, and HA initiate infection when it binds to receptors on host cells. The immune system of the infected animal targets sites on these molecules. Therefore, a virus with a novel HA can escape preexisting immune defenses—hence the pig deaths. Influenza viruses are named after their HA and NA components, as in “H1N1” or “H3N2.” Swine influenza viruses are most commonly of the H1N1 subtype, but other subtypes are also circulating in pigs (e.g., H1N2, H3N1, H3N2). Pigs can also be infected with avian influenza viruses and human seasonal influenza viruses as well as swine influenza viruses.
Fig: The influenza virus having genes from different species
Sometimes pigs can be infected with more than one virus type at a time, which can allow the genes from these viruses to mix. This can result in an influenza virus containing genes from a number of sources, called a “reassortant” virus. Although swine influenza viruses are normally species specific and only infect pigs, they do sometimes cross the species barrier to cause disease in humans. Both human and swine influenzas have been historically limited to only a few of these varieties. Birds, on the other hand, can be infected by every combination of the virus’s 15 HA genes and nine NA genes, forming a vast global reservoir of virus. And pigs have receptors for both human and bird flu virus, making them crock pots for new viral combinations.
The “classical” swine influenza virus discovered in 1931 is an H1N1 virus, related to the H1N1 that caused the 1918 pandemic. But in the past 5 years, at least three additional virus subtypes and four genotypes are identified in relation to that classical swine virus in North American pigs. The first new virus, the one that struck the North Carolina hogs in 1998, was an H3N2; in this case, genes had crossed from human viruses to pig viruses. The avian flu genes may hold clues to the viruses’ evolution. They code for two of the virus’s three polymerase proteins: PA and PB2. (A third polymerase, dubbed PB1, comes from either human or avian viruses, depending on the swine flu subtype.) All three polymerases are involved in viral replication, and they tend to do a sloppy job, allowing countless errors to slip by.
Scientists suspect these three imported polymerase genes to form a viral platform that triggering change in the influenza genome. In fact, H3N2 has continued to change, acquiring a succession of HA genes derived from human influenza viruses that circulated several years previously. By 2000, a new viral subtype is identified, an H1N2 that is a combination of the classical swine virus and the H3N2. This season’s variant is an H1N1 with the internal genes of an H3N2. Its HA gene, derived from the classical swine influenza virus, appears to be rapidly mutating. The amount of sequence divergence among enough certain isolates (>2000) is as much as different between classical H1N1 viruses isolated in the 1960s and those isolated in the early 1990s. If enough point mutations accumulate, that HA molecule could become unrecognizable to the immune systems of both pigs and humans. As these viruses can establish efficient human-to human transmission, it can cause an influenza pandemic. The impact of a pandemic caused by such a virus is difficult to predict: it depends on virulence of the virus, existing immunity among the people, cross protection by antibodies acquired from seasonal influenza infection and host factors. So vaccination is really difficult for such continually changing mutant viruses.
huge article.