Short comments about what I’ve been reading (besides several hundred influenza articles):

Hedskog, C., Mild, M., Jernberg, J., Sherwood, E., Bratt, G., Leitner, T., Lundeberg, J., Andersson, B., & Albert, J. (2010). Dynamics of HIV-1 Quasispecies during Antiviral Treatment Dissected Using Ultra-Deep Pyrosequencing PLoS ONE, 5 (7) DOI: 10.1371/journal.pone.0011345

The whole deep sequencing thing is going to profoundly change our knowledge of viral pathogenesis, as well as their ecology.

With highly mutation-prone viruses like HIV, hepatitis C virus, or influenza, our understanding of genome sequences has been based on the overall average genome — the average of a vast and diverse population. That average, that we’ve been calling the genome of these viruses, may not even exist as such, and certainly the minor variants that have been missed by traditional methods are also critically important, because they can explode out within a few days to take over the entire population, given the right set of circumstances. For example, if among those minor variants there are a few drug-resistant strains, then as soon as you treat the host, those variants may be able to take over.

In this paper, deep sequencing of people with HIV shows that drug-resistant variants do exist even before treatment, but they are normally very rare. They can take over during treatment with the particular drug, but when treatment is stopped they rapidly regress to rarity. This is presumably because the drug resistance makes the virus globally less fit (in the natural selection meaning of the term). When their more-fit brethren are destroyed by a drug these crippled, but drug-resistant, variants can grow out, but remove that selective pressure and the more wild-type versions take over once again.

As well as implications for treatment, this tells us something about viral reserves:

In most patients, drug resistant variants were replaced by wild-type variants identical to those present before treatment, suggesting rebound from latent reservoirs. 1


  1. Hedskog, C., Mild, M., Jernberg, J., Sherwood, E., Bratt, G., Leitner, T., Lundeberg, J., Andersson, B., & Albert, J. (2010). Dynamics of HIV-1 Quasispecies during Antiviral Treatment Dissected Using Ultra-Deep Pyrosequencing PLoS ONE, 5 (7) DOI: 10.1371/journal.pone.0011345[]