February 04, 2004

Influenza Genetics: or, Poultry's Revenge

A recent Nature news article about the avian flu reminded me of how interesting orthomyxovirus genetics is. The avian flu, as you may know, began as a pandemic in ducks and chickens in East and Southeast Asia late last year and has since jumped to humans.

New flus develop through two major pathways: minor antigenic shift and major antigenic drift. In both cases, the "antigens" in question are hemagglutinin and neuraminidase, the major surface proteins on influenzaviruses. Since hemagglutinin and neuraminidase protrude from the cell membrane (here's a picture, courtesy of the National Foundation for Infectious Diseases), they are the proteins that are recognized by the immune system. Flus are classified by what type of hemagglutinin and neuraminidase they have; for example, the Spanish flu pandemic of 1918 was caused by an H1N1 strain. Once you get the flu, you're immune to influenzaviruses with the same surface protein, but you can get the flu again if you're infected by a virus with different surface proteins. That's where minor antigenic shift and major antigenic drift come in.

Minor antigenic shift is simply the random mutation of the hemagglutinin and neuraminidase genes. Influenzaviruses have single-stranded RNA genomes that are copied with RNA polymerase. Because RNA polymerase is error-prone, the mutation rate in influenzaviruses is very high. This sort of genetic variability is fairly common among viruses--it's a major problem in vaccine development for a number of pathogens, including HIV.

More interesting is major antigenic shift. Major antigenic shift is the result of coinfection of a human cell by both human and animal influenzaviruses. When the progeny virii from these cells are packaged, they contain recombinant viruses that carry genes from both the human and animal viruses. Progeny virii carrying hemagglutinin and neuraminidase derived from the animal virus (novel antigens that allow the virus to escape immune system detection) and internal proteins from the human virus (which allow it to efficiently attack a human host) are capable of spreading in the human population. As you might expect, these hybrid flus tend to arise in areas where people live in close proximity with animals (usually birds or swine).

The clinical applications of this genetic information are just beginning to be utilized. A recent paper by Ferguson et al proposes a model for studying antigenic shift of flu viruses. Some countries, including Germany, are modifying existing vaccine preparation plans to include a greater focus on animal pandemics. In addition to these preventative measures, there's been a greater focus on devising flu treatments, though as yet none look any more useful than this "Receipt against Influenza" from Gentlemen's Magazine (circa 1743):

Take of Rue, Sage, Mint, Rosemary, Wormwood, and Lavender a handful of each, infuse them together in a Gallon of White Wine Vinegar, put them whole into a Stone Pot, closely covered up...set the Pot upon Warm Wood Ashes for eight Days; after which strain thro' fiine Flannel the Liquid, and put into Quart Bottles well cork'd, and in each a quarter of an ounce of camphire. With this Preparation wash your Mouth...snuff a little up your Nostrils, and carry about a bit of Sponge dipp'd in same, in order to smell especially when you are near any Place or Person infected.

Posted by Susan at February 4, 2004 07:15 PM

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