Monday, March 26, 2012

Luck Of The Draw



Photo Credit – CDC PHIL


# 6242



While it may seem curious to some, your humble flu blogger here at AFD has never – to his knowledge – ever suffered from a `classic’ bout of flu.


Oh, sure. I’ve had plenty of respiratory infections, albeit mostly upper respiratory. And a couple of times I’ve had what I’ve thought was probably influenza.


But I’ve never had the running fever, crushing body-aches, want-to-die kind of flu that many others seem to report.


I could just be lucky, I guess. 


But I’ve always figured I really wasn’t very susceptible to influenza. That when I’d had the flu, they had been relatively mild cases.  


Of course, I have no way of proving that . . .


But new research published in Nature by Wellcome Trust Sanger Institute lends credence to the idea that some people are genetically more likely to experience severe flu symptoms than others.


First some excerpts from the press release (worth reading in its entirety), then a link to the research article, then I’ll return with some other data suggestive of a genetic susceptibility to influenza.


Genetics of flu susceptibility

Researchers find gene that can transform mild influenza to a life-threatening disease

A genetic finding could help explain why influenza becomes a life-threating disease to some people while it has only mild effects in others. New research led by the Wellcome Trust Sanger Institute has identified for the first time a human gene that influences how we respond to influenza infection.


People who carry a particular variant of a gene called IFITM3 are significantly more likely to be hospitalised when they fall ill with influenza than those who carry other variants, the team found. This gene plays a critical role in protecting the body against infection with influenza and a rare version of it appears to make people more susceptible to severe forms of the disease. The results are published in the journal Nature.


A central question about viruses is why some people suffer badly from an infection and others do not. IFITM3 is an important protein that protects cells against virus infection and is thought to play a critical role in the immune system's response against such viruses as H1N1 pandemic influenza, commonly known as 'swine flu'. When the protein is present in large quantities, the spread of the virus in lungs is hindered, but if the protein is defective or absent, the virus can spread more easily, causing severe disease.

(Continue . . . )


IFITM3 restricts the morbidity and mortality associated with influenza

Aaron R. Everitt,Simon Clare,Thomas Pertel,Sinu P. John,Rachael S. Wash,Sarah E. Smith,Christopher R. Chin,Eric M. Feeley,Jennifer S. Sims,David J. Adams,Helen M. Wise,Leanne Kane,David Goulding,Paul Digard,Verneri Anttila,J. Kenneth Baillie,Tim S. Walsh,David A. Hume,Aarno Palotie,Yali Xue,Vincenza Colonna,Chris Tyler-Smith,Jake Dunning,Stephen B. Gordon,The GenISIS al.

Nature (2012)  doi:10.1038/nature10921



Although this research is the first to identify a specific gene that may make influenza a much more serious illness in some people than others, for some time there’s been evidence suggesting that heritable factors influence how people react to influenza.


In 2008, in the Journal of Infectious Diseases, we saw a study that suggested there might be a heritable susceptibility to death from the influenza virus.


Evidence for a heritable predisposition to death due to influenza.

Albright FS, Orlando P, Pavia AT, Jackson GG, Cannon Albright LA.

Abstract (extract)

Evidence for a heritable contribution to death due to influenza was examined using a resource consisting of a genealogy of the Utah population linked to death certificates in Utah over a period of 100 years. The relative risks of death due to influenza were estimated for the relatives of 4,855 individuals who died of influenza.


Both close and distant relatives of individuals who died of influenza were shown to have a significantly increased risk of dying of influenza, consistent with a combination of shared exposure and genetic effects. These data provide strong support for a heritable contribution to predisposition to death due to influenza.


While interesting, this study doesn’t provide us with a smoking gene.


However, the following year a PLoS ONE  research article doi:10.1371/journal. pone.0004857)  came a bit closer.  


Entitled Host Genetic Background Strongly Influences the Response to Influenza A Virus Infections by Srivastava B, Błażejewska P, Heßmann M, Bruder D, Geffers R, et al., it reports on the results of experiments utilizing seven inbred strains of lab mice that were exposed to influenza A viruses.


From the abstract:


The genetic make-up of the host has a major influence on its response to combat pathogens. For influenza A virus, several single gene mutations have been described which contribute to survival, the immune response and clearance of the pathogen by the host organism.


Granted, mouse models are often useful, but what happens in mice doesn’t always correspond to what happens with human physiology.


And last year, in Host Genetic Susceptibility to Avian Influenza, we saw an analysis of clusters of H5N1 infection in Indonesia that found that young age (under 30) and being a blood relative to the index case in a cluster, were both found to significantly increase the odds of catching the virus.


So there is anecdotal reason to believe that there may be genetic factors involved in either mitigating, or exacerbating, the effects of flu.


Never having suffered a `classic’ bout of flu admittedly gives me some hope that I might have some degree of built-in immunity to a pandemic virus.


But with an emerging or novel flu strain, who knows?


Of course, my good flu fortune may have more to do with my diligence in getting a seasonal flu shot every year, than with any genetic advantage.


But I can hope.