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

A/Brisbane/100/2014
GGATAATTCTATTAACCATGAAGACTATCATTGCTTT...

A/Brisbane/1000/2015
GGATAATTCTATTAACCATGAAGACTATTATTGCTTT...

A/Brisbane/1/2017
GGATAATTCTATTAACCATGAAGACTATCATTGCTTT...

... 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

nextstrain.org

joint project with Trevor Bedford & his lab

Emergence and dominance of SARS-CoV-2 variants

Successful variants are characterized by many mutations in S1

nextstrain.org/ncov/gisaid/global

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?

nextstrain.org/ncov/gisaid/global

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?