H1N1 Influenza not really so Benign...

H1N1 Influenza not really so Benign... 

[A recent journal of biology article highlights what is currently known about the (A)H1N1 influenza pandemic & its not so benign course-DQ]

Animal experiments indicate that influenza A(H1N1) 2009 causes relatively severe disease, yet the human disease has been reported as generally relatively mild. How can this discrepancy be explained?
First of all, although initial reports suggest that most human cases of influenza A (H1N1) 2009 infection are mild, particularly in the developed world, this is somewhat misleading as the symptoms are generally reminiscent of those observed with seasonal influenza infection (fever associated with upper respiratory tract illness) and even seasonal influenza is estimated to cause 250,000 to 500,000 deaths worldwide each year.

Second, up to 40% of infected individuals present with vomiting and gastrointestinal (GI) symptoms, which is higher than for seasonal influenza, and while there is no evidence as yet, this may be indicative of more extensive viral replication. This is actually consistent with three recent studies on the pathogenesis and transmission of influenza A (H1N1) 2009 in ferret models of infection [8,11,12].

All three studies showed that the pandemic strains exhibit more extensive replication in the respiratory tract, particularly the lower respiratory tract, of infected ferrets, as well as in mice [11,12], non-human primates and pigs [11]. Moreover, Maines and colleagues were able to isolate virus from the GI tract of infected ferrets, suggesting an explanation for the increased incidence of GI distress in infected people [12], although no virus has yet been detected in the GI tract of human cases.

All three studies also showed that influenza A (H1N1) 2009 caused more tissue damage in the lower respiratory tract than do typical seasonal influenza strains.

So are you saying the human disease actually isn’t mild?

In some cases, certainly it isn’t. It is important to note that the (H1N1) 2009 virus does cause severe infection in some people, including those who are otherwise healthy. While some fatal cases have been attributed to secondary bacterial infections or exacerbation of other health conditions, as is commonly seen in fatal cases of seasonal influenza in the elderly, an unusual feature of influenza A (H1N1) 2009 infection is severe viral pneumonitis, leading to acute respiratory distress syndrome, prolonged stays in intensive care units and extended use of mechanical ventilation or extracorporeal membrane oxygenation (ECMO) [13,14]. It is unclear what predisposes some people to mild versus severe complications.

And the tissue damage shown in the animal experiments? Isn’t that also indicative of severity?

That is not clear for humans. Although the animal experiments show that influenza A (H1N1) 2009 infection causes more extensive tissue damage than seasonal influenza infection, this could be relatively minor in humans, possibly because of the relatively low binding affinity of the influenza
A (H1N1) 2009 viral HA for human receptors. Human influenza viruses bind their target cells through recognition by the viral HA of cell surface glycoproteins that have sialic acid moieties linked to galactose in a α2,6 configuration.

When Maines and colleagues used a glycan array to compare glycan binding of HAs from influenza A (H1N1) 2009 and 1918 Spanish influenza [12], both showed the same binding specificity and pattern, but the influenza A (H1N1) 2009 HA bound with lower affinity than did the 1918 virus HA. This was attributed to amino acid differ ences in the HA binding site.

Lower binding affinity could affect the degree of inflammation and pathology caused by (H1N1) 2009 infection, so that although the virus seems to cause more tissue damage, the pathology may not be as extensive as that seen in infection with the more virulent 1918 Spanish influenza virus or highly pathogenic H5N1 viruses.