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


Richard Neher
Biozentrum, University of Basel


slides at neherlab.org/202012_MolecularVirology.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

Where does all that evolution happen?

Suppressive therapy and the latent reservoir:

Where is HIV hiding?

The latent proviral DNA reservoir

  • Viruses integrate but don't express → pro-viral DNA reservoir
  • Therapy fully suppresses virus replication, but interruption results in rebound
  • When is the reservoir established? How is it maintained?

p17 sequencing from PBMCs on fully suppressive therapy

Brodin et al, eLife, 2016

Proviral DNA mostly identical to pre-therapy RNA

Brodin et al, eLife, 2016

No evidence of ongoing evolution

Brodin et al, eLife, 2016, see also Abrahams et al, bioRxiv, 2019

Most proviral DNA originates from shortly after start of therapy

  • latent HIV → barcode of a T-cell lineage
  • all latent integrated virus derives from late infection
Brodin et al, eLife, 2016

Real-time tracking of SARS-CoV-2

  • hundreds of new sequences every day
  • more than 200k 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

Diversified into multiple global variants. Groups 20A/B/C have taken over.

Large scale spread of the virus

Regional variants emerged over the summer

Spread of a variant through travel and tourism

Acknowledgments

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

Acknowledgments

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