Ist die Evolution von Grippeviren vorhersehbar?


Richard Neher
Biozentrum, University of Basel


slides at neherlab.org/201803_SeniorenUni.html

Viruses

tobacco mosaic virus (Thomas Splettstoesser, wikipedia)

bacteria phage (adenosine, wikipedia)

influenza virus wikipedia

human immunodeficiency virus (HIV) wikipedia
  • Viren benötigen Wirtszellen zur Replikation
  • sind wenig mehr als Genom + Kapsid
  • ihr Genom ist 5-200Tsd Basen lang (+Ausnahmen)
  • zahlenmäßig dominierenden Organismen $\sim 10^{31}$

Influenza virus

  • Surface proteins hemagglutinin (HA) and neuraminidase (NA)
  • Influenza A virus
    • Common in birds and mammals
    • Many different subtypes defined by surface proteins
    • H3N2, H1N1, H7N9, H5N1
  • Influenza B virus
    • infects mainly humans
    • two lineages that split 30-40y ago
    • B/Victoria vs B/Yamagata

Human Influenza A viruses

slide by Trevor Bedford

Weekly numbers of positive influenza tests in the US by subtype

Data by the US CDC

Tracking virus spread and evolution by sequencing

A/Brisbane/100/2014
GGATAATTCTATTAACCATGAAGACTATCATTGCTTT...

A/Brisbane/1000/2015
GGATAATTCTATTAACCATGAAGACTATTATTGCTTT...

A/Brisbane/1/2017
GGATAATTCTATTAACCATGAAGACTATCATTGCTTT...

... thousands of sequences...

Phylogenetic analysis of viral sequences

RNA viruses have a high mutation rate. New mutations arise every few weeks.


  • Influenza virus evolves to avoid human immunity
  • Vaccines need frequent updates

nextflu.org

joint work with Trevor Bedford & his lab

Can we predicting influenza virus evolution?

  • Extrapolate current trends
  • Predict based on historical patterns
  • Use the branching pattern to predict success
  • Measure antigenic properties of circulating viruses
RN, Russell, Shraiman, eLife, 2014

Fitness inference from trees

$$P(\mathbf{x}|T) = \frac{1}{Z(T)} p_0(x_0) \prod_{i=0}^{n_{int}} g(x_{i_1}, t_{i_1}| x_i, t_i)g(x_{i_2}, t_{i_2}| x_i, t_i)$$
RN, Russell, Shraiman, eLife, 2014

Prediction of the dominating H3N2 influenza strain

  • no influenza specific input
  • how can the model be improved? (see model by Luksza & Laessig)
  • what other context might this apply?
 RN, Russell, Shraiman, eLife, 2014

nextstrain.org

joint work with Trevor Bedford & his lab

Summary

  • RNA viruses evolve fast
  • Viral lineages pick up mutations every few weeks
  • Genomic sequences can be used to track viral spread
  • Algorithms can predict future influenza virus variants
  • Automated real-time analysis can help fight the spread of disease

Joint work with....

  • Boris Shraiman
  • Colin Russell
  • Trevor Bedford

nextstrain.org

  • Trevor Bedford
  • Colin Megill
  • Pavel Sagulenko
  • Sidney Bell
  • James Hadfield
  • Wei Ding