Evolution of HIV and influenza viruses

Richard Neher
MPI for Developmental Biology - soon Biozentrum

slides at neherlab.org/201701_Biozentrum.html

Evolution of HIV

  • Chimp → human transmission ~1900 gave rise to HIV-1 group M
  • Diversified into subtypes that are ~20% different
  • evolves at a rate of about 0.1% per year
image: Sharp and Hahn, CSH Persp. Med.

HIV infection

chronic infection:
  • 10^8 cells are infected every day
  • the virus repeatedly escapes immune recognition
  • integrates into T-cell as latent provirus
image: wikipedia

HIV-1 sequencing before and after therapy

Zanini et al, eLife, 2015; Brodin et al, eLife, 2016

Population sequencing to track all mutations above 1%

  • diverge at 0.1-1% per year
  • almost full genomes coverage in 10 patients
  • full data set at hiv.tuebingen.mpg.de
Zanini et al, eLife, 2015; antibody data from Richman et al, 2003

Frequent version of previously beneficial mutations

  • HIV escapes immune systems
  • most mutations are costly
  • humans selects for different mutations
  • compensation or reversion?
Zanini et al, eLife, 2015

Fitness landscape of HIV-1

Zanini et al, Virus Evolution, 2017

Does HIV evolve during therapy?

Brodin et al, eLife, 2016

No evidence of ongoing replication

  • HIV-1 RNA from plasma before treatment started
  • HIV-1 DNA gag-p17 from PBMCs after many years of treatment
Brodin et al, eLife, 2016

No evidence of ongoing replication

Brodin et al, eLife, 2016

T-cell turnover is fast in untreated infection

  • latent HIV → barcode of a T-cell lineage
  • all latent integrated virus derives from late infection
  • untreated: T-cell lineages are short lived
  • on therapy: T-cell clones live decades
Brodin et al, eLife, 2016

Human seasonal influenza viruses

slide by Trevor Bedford

  • Influenza virus evolves 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

RN, Russell, Shraiman, eLife, 2014

Prediction of the dominating H3N2 influenza strain

RN, Russell, Shraiman, eLife, 2014

Drug resistance evolution in P. aeruginosa

  • ~3 week culture
  • OD measurement every 30 seconds
  • deep sequencing every 2 days
Regenbogen et al, biorxiv, 2016

HIV acknowledgments

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

Influenza and Theory acknowledgments

  • Boris Shraiman
  • Colin Russell
  • Trevor Bedford
  • Oskar Hallatschek

the group