Virology Select

Viruses are the scourge of mankind, causing devastating pandemics such as the 1918 Spanish flu and AIDS. This Virology Select highlights new studies that shed light on how viruses invade host cells so efficiently and how they evade the host immune response by stowing away in immune cells or by constantly changing their surface armor. The opening decade of the 21 st century witnessed the first flu pandemic in 40 years. Eerily enough, the culprit, an H1N1 influenza virus of swine origin, turns out to have important similarities to the H1N1 strain that caused the catastrophic 1918 Spanish flu, as two new studies now report (Wei et al., 2010; Xu et al., 2010). One of the most puzzling aspects of the 2009 H1N1 flu pandemic was that children and young adults were far more susceptible than individuals aged 65 or over (usually the population most at risk during seasonal flu outbreaks), suggesting that older individuals had some immunity. But flu viruses are known to evolve rapidly to evade the host immune response, and so it is unclear how older individuals could be partly immune to the 2009 H1N1 strain, given that almost a century separates it from the 1918 pandemic flu virus. One way that flu viruses evade the host immune response is by antigenic drift, which involves substitution of amino acids in a key surface glycoprotein called hemagglutinin (HA). HA enables flu viruses to bind and enter host cells and is a major target of antibodies produced by the host's immune system. Now, Wei et al. (2010) report the surprising result that the 1918 and 2009 H1N1 pandemic flu viruses have a remarkable degree of antigenic cross-reactivity despite being separated by almost a century. Mice injected with a DNA vaccine for the 1918 H1N1 virus produced antibodies that protected them against challenge with the 2009 H1N1 virus, and vice versa. These cross-neutralizing antibodies did not protect mice against infection with other circulating H1N1 viruses that cause seasonal flu. But which viral epitopes elicit these cross-neutralizing antibodies? A big clue comes from Xu et al.'s elegant structural study of the HA from both the 1918 and 2009 H1N1 strains. Using an antibody against the HA of the 1918 virus obtained from a patient who actually survived the Spanish flu, the investigators pinpointed an epitope in the HA head region of both viruses that bound the antibody. The epitope, close to …