Evolution and spread of Influenza, HIV, and SARS-CoV-2

Richard Neher
Biozentrum, University of Basel

slides at neherlab.org/202212_CBB.html

Human seasonal influenza viruses

slide by Trevor Bedford

Positive tests for influenza in the USA by week

Data by the US CDC

Virus genomes change rapidly through time




... hundreds of thousands of sequences...

Genome sequences record the spread of pathogens

in SARS-CoV-2 a new mutation accumulates about every 2 weeks
images by Trevor Bedford

  • Influenza viruses evolve to avoid human immunity
  • Vaccines need frequent updates

Predicting evolution

Given the branching pattern:

  • can we predict fitness?
  • pick the closest relative of the future?
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

Real-time tracking of SARS-CoV-2

  • thousands of new sequences every day
  • more than >14M sequences right now
  • comprehensive analysis require hours to days to complete
→ requires continuous analysis and easy dissemination
→ interpretable and intuitive visualization


joint project with Trevor Bedford & his lab

Emergence and dominance of SARS-CoV-2 variants

Successful variants are characterized by many mutations in S1


Remarkable patterns of rapid adaptation

nextstrain.org/ncov/gisaid/global, outbreak.info

Gradual shift from selection on transmission to immune escape

  • Until early-2021, seroprevalence was low to moderate
  • Delta infections and vaccination resulted in high seroprevalence in 2021
  • Variant success now is dominated by immune escape
Kleynhans et al, ourworldindata.org

So far, independent variants have dominated sequentially

  • Variant emergence likely through chronic infections
  • Strong dichotomy (until 2022): dramatic changes between variants, slow and steady within variants
  • Omicron variants are more dynamic
  • With BA.4/5 and BA.2 subvariants, we start to see second generation variants
What is driving this?
Can we predict?

To predict, we need to quantify selection by immunity

  • Given a population immunity "landscape", how much escape is caused by which mutation?
  • How variable are individual immune responses?
  • How does exposure history shape neutralization of different variants?
  • What is the contribution of chronic vs acute infections?
  • Does escape during chronic infection mediate inter-individual escape? It did for Omicron, but will this stay that way?
  • What is the contribution of chronic infections in other viruses?
van der Straten et al, biorxiv, 2022; Lee, ... Bloom, eLife, 2019


  • Fabio Zanini
  • Jan Albert
  • Johanna Brodin
  • Christa Lanz
  • Göran Bratt
  • Lina Thebo
  • Vadim Puller


  • Emma Hodcroft
  • Moira Zuber
  • Inaki Comas
  • Fernando Gonzales
  • Tanja Stadler
  • Sarah Nadeau
  • Tim Vaughan
  • Jesse Bloom
  • David Veesler


Trevor Bedford and his lab -- terrific collaboration since 2014

especially James Hadfield, Emma Hodcroft, Ivan Aksamentov, Moira Zuber, John Huddleston, and Tom Sibley

Data we analyze are contributed by scientists from all over the world

Data are shared and curated by GISAID