| Autor: |
Quadeer AA; Department of Electronic and Computer Engineering, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China., Barton JP; Department of Physics and Astronomy, University of California, Riverside, CA, 92521, USA., Chakraborty AK; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA. arupc@mit.edu.; Department of Physics, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA. arupc@mit.edu.; Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA. arupc@mit.edu.; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, 02139, USA. arupc@mit.edu.; Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA. arupc@mit.edu., McKay MR; Department of Electronic and Computer Engineering, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China. m.mckay@ust.hk.; Department of Chemical and Biological Engineering, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China. m.mckay@ust.hk. |
| Abstrakt: |
Vaccination has essentially eradicated poliovirus. Yet, its mutation rate is higher than that of viruses like HIV, for which no effective vaccine exists. To investigate this, we infer a fitness model for the poliovirus viral protein 1 (vp1), which successfully predicts in vitro fitness measurements. This is achieved by first developing a probabilistic model for the prevalence of vp1 sequences that enables us to isolate and remove data that are subject to strong vaccine-derived biases. The intrinsic fitness constraints derived for vp1, a capsid protein subject to antibody responses, are compared with those of analogous HIV proteins. We find that vp1 evolution is subject to tighter constraints, limiting its ability to evade vaccine-induced immune responses. Our analysis also indicates that circulating poliovirus strains in unimmunized populations serve as a reservoir that can seed outbreaks in spatio-temporally localized sub-optimally immunized populations. |
