Some Like it Hot

It’s now widely known that influenza type A viruses that usually infect ducks and other water birds can jump species to infect the human respiratory tract. Such transmission from birds to humans remains rare and tends to happen when some of the 16 subtypes of avian influenza manage to mutate by applying  proteins to their surfaces taken from human flu viruses.

So why is a tricky mutation the key to making the interspecies leap? It may be that bird flu likes it hot.

A new study by scientists from the University of North Carolina at Chapel Hill School of Medicine and Imperial College, London, in the U.K suggests that avian influenza finds the temperature in the human nose too cold a place to infect and replicate.

The study, published Friday, May 15, 2009 in the on-line, open access journal, PLOS Pathogens, points out that avian influenza viruses are adapted for growth at 104 degrees Fahrenheit (40 degrees Celsius). This is the gut temperature of host birds. But the human nose and throat, which are “the likely site of initial inoculation by influenza viruses, are maintained at a cooler temperature 32°C or 89.6˚F, suggesting that zoonotic transmission may be limited by temperature differences between the two hosts,” the authors write.

Lead author of the study was Margaret A. Scull, a graduate student working in the lab of senior author Raymond Pickles, Ph.D., of the UNC Cystic Fibrosis/Pulmonary Research and Treatment Center and associate professor of microbiology and immunology.

The research included growing cells from the human airway and infecting them with different human and avian influenza viruses, including H5N1, to see how well the viruses grew and spread.

“The human influenza viruses grew equally well in the cells whether they were maintained at 37 degrees Celsius, our core body temperature, or at 32 degrees Celsius, the temperature of the nose. In contrast, the four avian influenza viruses tested grew well at 37 degrees Celsius but grew very slowly at 32 degrees Celsius,” say the authors.

And when they created a mutated human influenza virus by adding a protein from the surface of an avian influenza virus, the mutated virus “struggled to thrive at 32 degrees Celsius”.  Scull and coauthors say this suggests that a mutated bird flu virus “would need to undergo further changes in order to adapt to the conditions in the human body.”

Seems it’s time to turn up the heat on this pathogen.

Les Lang

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New Angle on Angelman Syndrome

The 1967 movie hit, The Graduate, featured this now famous slice of dialogue between young Benjamin Braddock and a boozy Mr. McGuire:

Mr. McGuire:  I want to say one word to you.  Just one word.
Benjamin:  Yes, sir.
Mr. McGuire:  Are you listening?
Benjamin:  Yes, I am.
Mr. McGuire:  Plastics.
Benjamin:   Just how do you mean that, sir?

Today, at least among neurophysiologists, the new variation on that one-word notion is… “Plasticity.”

And that mean’s brain plasticity,  the normal ability of synapses to strengthen and weaken in response to changing neural activityand a  key component to experience-dependent brain maturation.  

Pyramidal cell. A type of neuron found in the cerebral cortex, the hippocampus and amygdala. These are the primary excitation units of the prefrontal cortex and spinal tract in mammals. Recent studies on pyramidal neurons have focused on topics ranging from neuroplasticity to cognition.

“When we have experiences, connections between brain cells are modified  so that we can learn,” says Ben Philpot, neuroscientist and professor of cell and molecular physiology at UNC.  “By strenghening and weakening appropriate connections between brain cells, a process termed ‘synaptic plasticity,’ we are able to constantly learn and adapt to an ever-changing environment.”

A collaborative research effort from the labs of Philpot and Duke University’s Mike Ehlers, MD, PhD, adds some experimental validation to the thought that the process is disrupted in people with neurodevelopmental disorders such as autism and Angelman syndrome.

The latter is a neurogentic disorder that occurs in one in 15,000 live births. Often misdiagnosed as as cerebral palsy or autism, characteristics include cognitive and developmental delay, severe mental retardation, minimal or no use of words, seizures, sleep disturbance, hand flapping and motor and balance disorders.

In studying a mouse model of the syndrome , in which the gene Ube3a is functionally deficient, the scientists found profound impairments in neocortical synaptic plasticity, suggesting that this may contribute to the learning impairments in people with Angelman syndrome.

 But the study revealed a tantalizing finding: it showed that normal brain plasticity can be restored after brief periods of  sensory (visual) deprivation.

“This raises the remarkable possibility that brain cells in Angelman syndrome patients maintain a latent ability to reverse their plasticity defects,” says Philpot, thus raising the possibility of effective therapies for the disorder, behavioral, pharmacological, or genetic.

See: Yoshiro, Koji, et al, “Ube3a is required for experience-dependent maturation of the neocortex.”  Nature Neuroscience, publised online May 10, 2009.

Photo credit:  Philpot lab.

Les  Lang