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Background Antigenic drift and the generation of viral quasispecies Some RNA viruses form a quasispecies--a set of related viral variants that coexist in field populations and even within single infected individuals (reviewed in [ 1, 2, 3, 4, 5]).
Attributed in part to antigenic drift are the moderately high failure rate and the short-lived efficacy of influenza vaccines [ 6], the failure of synthetic foot-and-mouth disease virus vaccines [ 7], and the inability of recombinant HIV vaccines to provide complete protection against field strains of the virus [ 8].
Similarly, much of the observed variability of glycoprotein 120 (gp120), the principal surface antigen of HIV, is thought to reflect antigenic drift [ 14, 15, 16, 17].
The correlation of intra-patient viral diversity with immune response strength has been cited as evidence that the immune response is a selective factor in HIV antigenic drift [ 18, 19, 20, 21, 22].
proposed four antigenic sites where field and laboratory mutations could be grouped on the HA surface [ 41].
These putative antigenic sites are indicated in Figure 1and the right side of Figure 2.
Positively selected variants are correlated (Fisher's exact test) with antigenic site A (p = 5.
12 × 10 -3), and antigenic site C (p = 1.
We believe the lack of positively selected variants spanning antigenic site D may explain a decades-old puzzle.
At the time that the antigenic sites were proposed, residues in and around the trimer interface were variable and found on the monomer surface, so they were grouped and labeled as antigenic site D even though it was unclear how site D was recognized by Ab [ 41].
That is, while the trimer-buried portion of antigenic site D includes the sound and fury of variability, it signifies nothing.
While QUASI finds that antigenic sites A-C are significantly associated with positively selected variation, this association may be a simple consequence of the sites' surface exposure.
There are positively selected variants outside the antigenic sites, and there are subregions of the antigenic sites where variation is negatively selected.
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