Two types of linkages between the terminal sialic acid residue and the penultima
ID: 65254 • Letter: T
Question
Two types of linkages between the terminal sialic acid residue and the penultimate galactose residue are found in nature: alpha(2,3) linkages and alpha(2,6) linkages (Figure 11.3). lnfluenza viruses isolated from humans preferentially bind alpha(2,6) linkages. lnternational surveillance programs monitor influenza outbreaks and analyze the viruses for their antigenic properties in an effort to prevent the occurrence of a pandemic. To obtain sufficient material for analysis, virus isolated from patients is often grown in chicken eggs, cells that predominantly express the alpha(2,3) type oiiinkage. Do you think the virus purified from chicken eggs will accurately reflect the virus isolated from the infected patients?
Explanation / Answer
The 2009 swine-origin H1N1 influenza virus is known to bind both alpha(2,3) and alpha(2,6) linked sialic acids. This is consistent with the ability of the virus to cause lower respiratory tract disease. The D225G change might be expected to increase affinity for alpha(2,3) linked sialic acids. However, it is not known if increased binding affinity correlates with higher infectivity and pathogenicity. It’s equally likely that high-affinity binding might restrict the movement of the virus in lung tissues by causing retention of the virus on nonsusceptible cells. One explanation for the sporadic emergence of influenza viruses with the D225G change is that they are selected for in the lower respiratory tract where alpha(2,3) sialic acids are more abundant than in the upper tract. Such selection might be facilitated in individuals with compromised lung function.
There is an alternative explanation for the isolation of at least some influenza viruses with the D225G change: it is selected by propagation in embryonated chicken eggs. This selection occurs because cells of the allantoic cavity of chicken eggs have only an alpha(2,3) linked sialic acids. A change in receptor specificity does not occur when viruses are propagated in MDCK (canine kidney) cells, which possess sialic acids with both alpha(2,3) and alpha(2,6) linkages.
In contrast, the propagation of human viruses in embryonated chicken eggs consistently leads to the selection of receptor-binding variants with increased affinity for Neu5Ac(2–3)Gal receptors on cells of the allantoic membrane (“egglike” HA variants). Although viruses grown in Madin-Darby canine kidney (MDCK) cells, which express receptors with both types of linkages, do not readily acquire such affinity for Neu5Ac(2–3)Gal-receptors, those recovered from chicken eggs do show a growth advantage in MDCK cells over viruses lacking egg-selected changes in the HA.
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