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H1N1 (Swine Flu) Mutant Gene D222G Linked To Fatal Cases Might Have Disabled The Clearing Mechanism Of Lungs

October 28, 2010

A new study in the November issue of Virology suggests that suggests that the mutant virus, known as D222G, could have impaired the lungs’ ability to clear out germs. This mutant gene was linked to fatal cases that enabled it to infect a different subset of cells lining the airway, according to this new research.

The researchers behind the study, from Imperial College London, the Medical Research Council National Institute for Medical Research and the University of Marburg said the findings highlight the potential for deadlier strains of flu to emerge and spread.

The 2009 pandemic of H1N1 influenza caused thousands of deaths worldwide, but the majority of cases were relatively mild. A variant of the virus carried a mutation termed D222G in a protein on the surface of the virus, and people infected with this variant were more likely to have severe and fatal illness.

A WHO report issued on December 28, 2009 noted that the D222G mutation was found in less than two in every hundred cases of 2009 pandemic flu, but was responsible for around seven in every hundred deaths. (http://www.who.int/csr/resources/publications/swineflu/h1n1_d222g/en/index.html)

Viruses infect cells by attaching to receptor molecules on the cell surface. Different receptors are present on different cell types, and a virus can only infect cells that have the right receptors for the protein on its own surface. The new research shows that flu virus with the D222G mutation can bind to a broader range of receptors in the airway, including receptors that are present on cells called ciliated cells. These cells, found in the lining of the airway, have hair-like projections called cilia. The cilia sway back and forth to move mucus with trapped particles upward toward the mouth, and this is normally swallowed or coughed up. When ciliated cells become infected, the cilia stop moving and this vital clearance function is impaired. Inhaled viruses and bacteria can then reach the lung more easily, where they can potentially cause pneumonia.

The net-net of this finding is that if the D222G mutant virus was to acquire the ability to spread more widely, the consequences could be very serious. The virus is constantly evolving, and it’s possible that a new form as dangerous as the 1918 pandemic could emerge.

http://www3.imperial.ac.uk/newsandeventspggrp/imperialcollege/newssummary/news_22-10-2010-11-43-13

http://jvi.asm.org/cgi/content/abstract/84/22/12069

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