Norovirus To the extent that I’m a virologist at all, I’m mostly a DNA virus kind of guy, so I can’t give a lot of deep background about noroviruses. I know what everyone knows — noroviruses are a major cause of gastoinstestinal symptoms, especially where people congregate in groups — cruise ships are notorious sites for norovirus epidemics — but also pretty much anywhere; hundreds of thousands of people are infected weekly in Britain at the moment, for example. The virus is a smallish RNA jobbie (a member of the caliciviruses: single-stranded positive-strand RNA, a bit over 7500 bases long). And it turns out to be extraordinarily interesting in its evolution.

This is from
Lindesmith, L.C., Donaldson, E.F., LoBue, A.D., Cannon, J.L., Zheng, D., Vinje, J., Baric, R.S. (2008). Mechanisms of GII.4 Norovirus Persistence in Human Populations . PLoS Medicine, 5(2), e31. DOI: 10.1371/journal.pmed.0050031
They were able to track the sequences of noroviruses involved in epidemics over the past 20 years, and analyzed them functionally. They found two functional changes over time: First, the viruses shift their targets (so that people who are resistant to infection today, may not be in five years time); and second, the viruses drift antigenically, so they avoid the previous year’s immune response.

Both of these evolutionary directions surprise me, at any rate. First, I’m not used to viruses being able to blithely switch their receptor over time; and second, my impression has been that immunity to noroviruses is so weak and transient that the virus wouldn’t need to worry about last year’s immunity to any significant effect.

The receptor thing is apparently because noroviruses use a family of carbohydrates as their receptor; the carbohydrates are variable among the human population, so that:

Variation in the capsid carbohydrate-binding domain is tolerated because of the large repertoire of similar, yet distinct HBGA carbohydrate receptors available on mucosal surfaces that could interface with the remodeled architecture of the capsid ligand-binding pocket.

Norovirus (Wellcome)As for the transient immunity, it seems that I’m a little out of date, though I have company — the accompanying review article in the same issue of PLoS Medicine says:1

Acquired immunity is not thought to last until a subsequent norovirus season, though a few individuals may acquire longer-lasting immunity. With these factors combined, one might think that immune selection pressure would be rather transient-only heavy at the end of a season-and that an evolutionarily stable strategy for norovirus might be to wait out the summer low season and attack again when population immunity has waned. This is not what Baric and colleagues have found.

It’s true that early studies on noroviruses did show only transient immunity, but apparently a number of recent studies have shown that long-term immunity is possible. 2 Critically, in the years following outbreaks of a new norovirus strain, infection rates dropped, suggesting that at least some herd immunity exists.3 That being the case, it’s not surprising that noroviruses evolve to escape from this pressure:

not only does antigenic drift occur in the capsid region of GII.4 norovirus strains over time, but that the variation greatly influences the ability of preexisting herd immunity to neutralize extant strains, based on carbohydrate blockade assays.

Finally, just to make Larry Moran happy, the authors point out that most of the changes in noroviruses over time are due to random drift:

In our analyses, the shell domain appears to be evolving by random drift, as only 5% of changes are informative (i.e., became fixed in the population).

  1. Lopman B, Zambon M, Brown DW (2008) The Evolution of Norovirus, the “Gastric Flu”. PLoS Med 5(2): e42 doi:10.1371/journal.pmed.0050042[]
  2. Lindesmith L, Moe C, Lependu J, Frelinger JA, Treanor J, et al. (2005) Cellular and humoral immunity following Snow Mountain virus challenge. J Virol 79: 2900-2909.
    Siebenga JJ, Vennema H, Duizer E, Koopmans MP (2007) Gastroenteritis caused by norovirus GGII.4, The Netherlands, 1994-2005. Emerg Infect Dis 13: 144-146.
    Lindesmith L, Moe C, Marionneau S, Ruvoen N, Jiang X, et al. (2003) Human susceptibility and resistance to Norwalk virus infection. Nat Med 9: 548-553.[]
  3. Siebenga JJ, Vennema H, Renckens B, de Bruin E, van der Veer B, et al. (2007) Epochal evolution of GGII.4 norovirus capsid proteins from 1995 to 2006. J Virol 81: 9932-9941[]