Jan Felix Drexler

Institute of Virology, University of Bonn

New insight into HBV evolution

How old are hepadnaviruses – endogenous bird & reptile

variants well >60 million years

Suh, PLoS Gen, 2015

Consistent with diverse hepadnaviruses in lower

vertebrates

Dill, J Virol, 2016

Mammal-like?

Hepatology, 2012

Slow long-term evolution:

Mummy HBV

near-identical to contemporary

strains

Extant bats are old mammalian lineages – introduction of

ancestral HBV into mammals?

Simmons, Science 2005

Screening of 3,000 bats for HBV

Drexler/Geipel et al., 2013, PNAS

Roundleaf bat H. Ruber RBHBV

Tent-making bat U. Bilobatum TBHBV

Horseshoe bat R. Alcyone HBHBV

natalie's Life List, inaturalist.org

3 viruses

1

2 3

Relevance of bats - Chiropteran hosts harbor

largest hepadnavirus diversity within mammals

Rasche et al., Curr Opinion Virol, 2016

Two HBV species in primates: HBV WMHBV

Primate HBV ancestors: Acquisition of bat viruses by

monkeys?

Rasche et al., Curr Opinion Virol, 2016

Lack of studies into New World non-human

primates

123 animals 9 species

4 studies in 45 years

Brazil: 5th largest country Highest primate diversity

worldwide

Brazil 118 species

Screening of ca. 100 NHP A new primate HBV species:

CMHBV

Dominguez/König/Rasche et al., unpublished

Potentially chronic infection: core deletions and no signs

of inflammation

Dominguez/König/Rasche et al., unpublished

Deep HBV sister lineages in new world monkeys

Dominguez/König/Rasche et al., unpublished

Evidence for ancient co-speciation of primate

hepadnaviruses and their hosts – but not for HBV

Dominguez/König/Rasche et al., unpublished

Ancestral state reconstructions

Primate hepadnavirus origins in NHP HBV in humans?

Dominguez/König/Rasche et al., unpublished

Hypothesis testing

HBV may have evolved in hominoid ancestors 17 million years ago

Dominguez/König/Rasche et al., unpublished

You are here!

No evidence for ancestry of F/H

in American monkeys

Introduction

along human migration?

Dominguez/König/Rasche et al., unpublished

In sum • Hepadnaviruses are an extremely old

virus family • Primate hepadnaviruses may be the

result of a host switch millions of years ago

• HBV likely evolved in hominoid ancestors, preceding the human stem lineage

• Divergent New World genotypes F/H may originate from pre-historic human migration

Virology, Bonn Christian Drosten Victor Max Corman Monika Eschbach-Bludau Sebastian Brünink Tobias Bleicker Andrea Rasche Marcel Müller FLI, Riems Rainer Ulrich Martin Beer

Ulm Elisabeth Kalko Marco Tschapka Stellenbosch Wolfgang Preiser Sonja Matthee Kruger NP Danny Govender

EMC, Rotterdam Ab Osterhaus Thijs Kuiken Debby van Riel JMA van den Brand Virology, Berlin Detlef Krüger Virology, Giessen Dieter Glebe Virology, Heidelberg, Ralf Bartenschlager Virology, Hannover Georg Herrler Bernhard Nocht Institut, HH Thomas Kruppa Jonas Schmidt-Chanasit RIVM, Netherlands Chantal Reusken ILRI, Kenya Jörg Jores

Funded by

KCCR, Kumasi Augustina Annan Samuel Oppong Mexico Álvaro Aguilar Setién Veterinary Medicine, Salvador Roberto Franke Eduardo Netto Chumakov Institute, Moscow Alexander Lukashev CIRMF, Franceville Eric Leroy AFMB, Marseille Bruno Coutard