Bats as reservoirs of emerging pathogens

Prof. Dr. Steven Van GuchtViral DiseasesWIV-ISPSSID, Brussels, 19/05/2016

WIV-ISP | Rue Juliette Wytsmanstraat 14 | 1050 Brussels | Belgium

T +32 2 642 xx xx | F +32 2 642 xx xx | xx@wiv-isp.be | www.wiv-isp.be

What are bats?

Megachiroptera:

1 family

old world fruit bats

flying foxes (vleerhonden)

Microchiroptera:

17 families

worldwide

echolocation, hibernation

Hands developed into wings

20% of 5000 species of mammals

Peridomestic

Old world fruit bat

Bumblebee bat

The problem with bats

1932: Rabies

1996: Hendra

2000: Nipah

2003: SARS → Chinese horse

shoe bat was

reservoir!

2005: Ebola

2007: Marburg

2007: Reovirus (Meleka, Kampar)

2012: MERS

Next ?

What is special about bats?

• Good reservoir species

• High virus diversity (cfr rodents):

2007-2013: >248 novel viruses discovered*

Database for bat viruses: www.mgc.ac.cn/DBatVir/

• Pathogens exceptionally lethal for other

mammals, mild or subclinical in bats

• Ancestral host for important mammalian virus

families and genera

*Young CC, Olival KJ. 2016. PLoS One. 2016 Feb 11;11(2):e0149237.

Bats as ancestral host

Most likely:

Lyssavirus (Rabies)

Alpha-and beta-coronavirus (MERS, SARS, 229E, NL63)

Filovirus (Ebola, Marburg)

Major paramyxoviruses, including Mumps virus and RSV

Possibly also:

Hantavirus (together with shrew and moles)

Hepandavirus, including HBV

Hepacivirus (HCV ancestor)

Bats live in dense colonies

Bracken cave, Texas: 20 million Mexican-free tailed bats

Congress Avenue bridge Austin: 1 million

= largest colonies of mammals

Mumbai: 1 human/43 m2

Bracken cave: 2222 bats/m2

Ancient order: 60 million years old

primitive mammalian characteristics, little evolutionConserved ancient cell receptors, enzymes,...Co-evolution virus - bats

From: Gids van de vleermuizen van Europa, Lina, Tirion, Baarn, 2001

SARS CoV: ACE-2

MERS CoV: DPP4

Conserved mammalian receptors

Hendra and Nipah:

ephrin B2 (arteries,

neurons)

Metabolism

• Specific traits associated with flight:

High body temperature (41°C): cfr fever

Heigthened DNA repair mechanisms and ROS

scavenging (longevity)

• Low body temperature during hibernation and

torpor (1-2°C): suppression immunity

Immune system

• Similar immune cells, antibody classes

• Conserved pattern recognition receptors

TLR3, RIG-I, MDA5,…

• IFN system:

Constitutive expression of IFN-alpha

No hyperinflammation

Better control of virus replication?

• Favours persistent infections (?)

Zhou P et al. 2016 PNAS 113(10): 2696–2701

Genus Lyssavirus: rabies

Movement of bats caused worldwidedissemination

11 out of 12 species circulate in bats

Bat rabies in Europe

European bat lyssavirus-1 (EBLV-1): Eptesicus serotinus

EBLV-2: Myotis daubentonii

30 rabid bats per year

Spill over infections in sheep, stone marten, cat

4 lethal cases in humans since 1977

Bat rabies in Belgium

• ± 40 bats examined/year

Pipistrellus (84%)

Eptesicus (6%)

Myotis (3%)

• No local case (yet)

• 2010: 1 positive bat from Spain

• Low sensitivity surveillance

• 10 people/year receive prophylaxis

after bat bite/scratch

Epistat: 2008-2016, 331 bats

examined

Photographer bitten by rabid bat in

2010

The vampire bat: what’s in a name?

Invasion of humans in endemic foci: gold rush, deforestation

Animal husbandry

Disturbance ecosystem = disturbance equilibrium in disease transmission

Vampire bats of the Amazone

Johnson N. et al. Viruses. 2014 Apr 29;6(5):1911-28.

Deforestation

Fruit bats as reservoirs of Ebola

Leroy et al. Fruit bats as reservoirs of Ebola virus. Nature. 2005 Dec 1;438(7068):575-6.

Picture from Mishra B. Indian J Med Microbiol 2014;32:364-70

6% of hammer-headed bats have ZEBOV antibodies

Hammer-headed bat (Hipsignathus monstrosus)

Egyptian fruit bat (rousette)

2007 Uganda: Outbreak Marburg hemorragic fever in miners

5000/100000 bats in 1 cave subclinically infected

Ebola epidemic 2014-2015

Index case: 1 boy in guinea, sick in dec 2013

Source of infection: bat-infested hollow tree ?

28652 cases, 11325 deaths, 10 countries

Marí Saéz A et al. Investigating the zoonotic origin of the West African Ebola epidemic. EMBO Mol Med. 2014

Dec 30;7(1):17-23.

FAO warns against bat hunting

and bushmeatHIV-1

HIV-2

HTLV-1

HTLV-2

Ebola

Hendra virus Australia

Acute respiratory disease and encephalitis

Bats > horses > humans

Since 1994: >11 outbreaks horses, 4 human deaths/7 cases

Fence to keep horses out of the “drip” zone

Since 2012: vaccine for horses

Nipah virus

Acute respiratory disease and fatal encephalitis

Malayasia 1998: bats > pigs > farmers (109 deaths/283 human cases)

Bangladesh >33 outbreaks: date palm sap

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Origin of SARS CoVHorseshoe bats

High diversity of SARS-like CoV

WIV1 isolate: 95% identity

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Civet cat: little genetic variation of isolatesvery susceptible: high virus titers= amplification host

late epidemic strainearly middle

29 nucleotide deletionin ORF8

Animal market

South-east China

MERS CoV

• 2012-2016: 642 deaths/1728 cases

• Reservoir is dromedary camel (80% seropositive)

• Bat is ancestral host:

- >20 years ago in East Africa: Bats > camels

- Bats are probably not a direct source for humans

- MERS-like CoV: 80% identity

Conclusions

• New biomedical insights: virus immunology, longevity, hearing ,….

• In Europe: mainly useful animals (insectivores)

• (Sub)Tropics: deforestation and urbanisation will continue to drive spill-over and outbreaks of forest pathogens

• Metagenomics is rapidly creating insights in wide diversity of viruses in nature

• Major zoonotic events: only 1 or few species, under specific circumstances and in specific regions

Friend or foe?

Thanks for your attention!