Descubren por qué la influenza H1N1 se propaga de manera ineficiente

Un equipo del Instituto de Tecnología de Massachusetts (MIT) y los centros de control y prevención de la enfermedad (CDCs) han encontrado una explicación genética del por qué el nuevo virus de la influenza porcina H1N1 se ha diseminado de persona a persona de manera menos efectiva que otros virus de la influenza.
La cepa H1N1 que circula en el mundo esta primavera, tiene una forma de proteína de superficie que se combina de manera ineficiente a los receptores que se encuentran en el tracto respiratorio humano, reportó el equipo en la edición online del 2 de julio de la revista Science.
“Aunque el virus es capaz de unirse a receptors humanos, parece claramente que esta unión está restringida”, dice Ram Sasisekharan, quien junto a colaboradores ha estado investigando activamente los virus de la influenza y es el autor principal del trabajo del MIT.
Esta unión restringida o débil unida a una variación genética en una enzima polimerasa del H1N1 que fue reportada por primera vez hace tres semanas por investigadores del MIT en Nature Biotechnology, explica por qué el virus no se ha diseminado con tanta eficiencia como el de la influenza estacional, dice Sasisekharan
http://www.eurekalert.org/pub_releases/2009-07/miot-mac070109.php

However, flu viruses are known to mutate rapidly, so there is cause for concern if H1N1 undergoes mutations that improve its binding affinity.
“We need to pay careful attention to the evolution of this virus,” says Sasisekharan.
On June 11, the World Health Organization declared a level 6 pandemic alert for H1N1. More than 300 people have died and more than 70,000 people have been infected, according to the WHO.
Genetic variation
Sasisekharan and CDC senior microbiologist Terrence Tumpey have previously shown that a flu virus’s ability to infect humans depends on whether its hemagglutinin protein can bind to a specific type of receptor on the surface of human respiratory cells.
In the new Science paper, Sasisekharan, Tumpey and colleagues compared the new H1N1 strain to several seasonal flu strains, including some milder H1N1 strains, and to the virus that caused the 1918 flu pandemic. They found that the new strain, as expected, is able to bind to the predominant receptors in the human respiratory tract, known as umbrella-shaped alpha 2-6 glycan receptors.
However, binding efficiency varies between flu strains, and that variation is partly determined by the receptor-binding site (RBS) within the hemagglutinin protein. The team found that the new H1N1 strain’s RBS binds human receptors much less effectively than other flu viruses that infect humans.
The researchers also found that the new H1N1 strain spreads inefficiently in ferrets, which accurately mimics human influenza disease including how it spreads or transmits in humans. When the ferrets were in close contact with each other, they were exposed to enough virus particles that infection spread easily. However, when ferrets were kept separate and the virus could spread only through airborne respiratory droplets, the illness spread much less effectively.
This is consistent with the transmission of this virus seen in humans so far, says Sasisekharan. Most outbreaks have occurred in limited clusters, sometimes within a family or a school but not spread much further.
“One of the big payoffs of long-term investments in carbohydrate biology and chemistry research is an understanding of the relationships between cell surface carbohydrate structure and viral infectivity,” said Jeremy M. Berg, director of the National Institute of General Medical Sciences of the National Institutes of Health, which partly funded the research. “Tools developed in building such understanding help in the response to events like the recent H1N1 outbreak.”
Second mutation
The researchers also pinpointed a second mutation that impairs H1N1’s ability to spread rapidly.
Recent studies have shown that a viral RNA polymerase known as PB2 is critical for efficient influenza transmissibility. (RNA polymerase controls the viruses’ replication once they infect a host.) The new H1N1 strain does not have the version of the PB2 gene necessary for efficient transmission.
MIT researchers led by Sasisekharan first reported the PB2 work in the June 9 online issue of Nature Biotechnology. That study also found that the new H1N1 strain has substantial genetic variability in the proteins targeted by current vaccines, making it likely that existing seasonal vaccines will be ineffective against the new strain.
Moreover, the researchers discovered that the new strain might just need a single change or mutation that could lead to inefficient interaction with the influenza drug oseltamivir, commonly known as Tamiflu, raising the possibility that strains resistant to Tamiflu could emerge easily.