What are zoonoses?

• Most pandemics involving viruses originate in animals
• Novel viruses are “driven to emerge by ecological, behavioural, or socioeconomic changes.” (E. C. Smith and Denison 2013)
• Sometimes claimed that humans are “coming into contact with wild animals more frequently than in the past”
• Most human contact is with domestic animals

What are the roles of humans and wildlife?

• Livestock accounts for more biomass (cells) than all humans on earth; More than 50% greater than humans 10x greater than all wildlife.
• I.e humans + livestock ~ 15 times the total wildlife biomass (cells in which viruses can replicate)
• Even so, most viral genomic diversity must be found in wildlife (~ 5k mammal 10K bird species).
• Studies on viruses that affect neither livestock nor humans remain vanishingly small part of the literature

Summary of the role of livestock.

• Source of most diversity is wildlife (15 thousand species vs “handful”)
• But the most likely proximal source of infection is livestock
• Wildlife -> livestock <-> humans
• Livestock including farmed animals + household pets

What role do co-infections and recombination play?

• Wildlife provides a very large pool of unsequenced genetic material
• Co-infections between endemic viruses of domestic animals and “novel” (i.e. previously unknown sequences) likely source of recombinants
• Availability of sequences key to understanding “novel” recombinants
• Availability bias: Do we have all the sequences? .. Clearly NOT

Influenza as an example of a zoonosis

• Influenza A, B, C and D are considered as viral genera (Krammer et al. 2018)
• Enveloped negative sense single strand RNA viruses with a segmented genome
• Cell entry through glycoproteins: haemagglutinin (HA) and neuraminidase (NA)
• 16 antigenically different HA and 9 antigenically different NA serotypes
• Interchange (recombination) of genomic RNA segments occurs when two viruses of the same type infect the same cell.

Nomenclature of flu strains

• Named after combination of H and N e.g (H1N1)
• Strains or variants

How does flu “spillover” occur?

(Krammer et al. 2018)

Is HIV a zoonosis?

• HIV probably evolved from simian immunodeficiency virus (SIV),
• SIV or HIV (post mutation) was transferred from non-human primates to humans in the recent past
• May also have a reservoir in bats

A breakdown of HIV transmission from animals

(Sharp and Hahn 2011)

What is Ebola?

• There are 6 known species of Ebola virus.
• Four produce disease in humans
• Zaïre ebolavirus (EBOV)
• Sudan ebolavirus (SUDV)
• Tai Forest (TAFV) (formerly known as Ebola Ivory Coast)
• Bundibugyo ebolavirus (BDBV)

How does Ebola spread from animals?

(Feldmann and Geisbert 2011)

Where did Ebola emerge?

Characteristics of the coronaviruses SARS and MERS

• SARS arose in 2002
• By July 2003 8,096 reported cases, including 774 deaths in 27 countries
• No more infections were detected after July 2003
• June 2012: MERS-CoV identified in Saudi Arabia
• Led to 1,728 confirmed cases and 624 deaths
• Both had strong nosocomial elements

How do coronaviruses SARS and MERS infect humans?

Why are bats considered to be so important?

• ~ 2000 species of rodents: ~ 40% of all mammals
• ~ 925 species of bats: ~ 20%
• Most likely source of zoonoses would appear to be rodents
• However, bats are both highly diverse, highly mobile and colonial
• Proximity of insectivorous bats to humans goes largely unnoticed (nocturnal)

Bat viral diversity

• Extremely high (Wu et al. 2016)

How many studies of bat coronavirus diversity?

• Similar sequences to SARS found throughout the world (Drexler, Corman, and Drosten 2014a)

Illustrative studies in bats

• Multiple examples of coronavirus diversity in bats throughout the world (see reference section for the article titles and links)

• A. Balboni et al. (2011) Andrea Balboni et al. (2012) Monchatre-Leroy et al. (2017) Hu et al. (2017) Rizzo et al. (2017) Hayman et al. (2013) Plowright et al. (2014) Mendenhall et al. (2019) Lacroix et al. (2020) Wong et al. (2019)Anthony et al. (2013) Tao and Tong (2019) Drexler, Corman, and Drosten (2014b) P. C. Y. Woo et al. (2012) C. S. Smith et al. (2016) Patrick C. Y. Woo et al. (2006) Lau et al. (2015) V. M. Corman et al. (2015) Drexler et al. (2011) De Sabato et al. (2019) Kivistö et al. (2020) Musso et al. (2020) Pauly et al. (2017)

Example from Luxembourg

(Pauly et al. 2017)

• Severe acute respiratory syndrome (SARS)-related Betacoronavirus strains were shed by Rhinolophus ferrumequinum
• “The high similarity of the spike gene sequences of these viruses with mammalian Betacoronavirus 1 strains may be of concern. Both the SARS-related and Betacoronavirus 1 strains detected in bats in Luxembourg may cross the species barrier after a host adaptation process.”

Drexler et al. (2010)

• Rhinolophids carried severe acute respiratory syndrome (SARS)-related CoV at high frequencies and concentrations (26% of animals are positive; up to 2.4 copies per gram of feces), as well as two Alphacoronavirus clades, one novel and one related to the HKU2 clade.
• All three clades present in Miniopterus bats in China (HKU7, HKU8, and 1A related) were also present in European Miniopterus bats.

Muth et al. (2018)

• “We have previously described the detection of SARS-related CoV in Rhinolophus in Bulgaria”"
• To further investigate the presence of ORF8 in SARS-related CoV in Europe, we analyzed fecal samples from rhinolophid bats in Spain, Bulgaria, Italy, as well as Slovenia
• All five Rhinolophus species commonly encountered in Europe were tested positive for coronavirus RNA
• The variant termed rSCV8 contained a complete ORF8 as encountered in bats, civet cats, as well as in early human cases of SARS

Inter genus host switches

(Latinne et al. 2020)

How does spillover occur?

(Cui, Li, and Shi 2019)

Spillovers

• Highly likely in numerous other viruses
• Most go undetected
• Self limiting or asymptomatic

Recombination in SARS intermediate host?

(Graham and Baric 2010)

Can cats be intermediate hosts?

• Civet cats are farmed in China, but comparatively rare
• Domestic cats are ubiquitous
• Feline ACE2 reacts with SARS-Cov as well as human ACE2 (Guo et al. 2008) (Jo et al. 2020)

What role did pangolins play?

• Pangolin theory based on a single sequence (Segreto and Deigin 2020)
• No evidence in wild populations (Lee, Mallick, and Lei 2020)

Muth et al. (2018)

V. Corman et al. (2020)

What are the implications of zoonotic origin?

• Current situation was difficult to avoid
• Arose through natural evolutionary processes (extended Darwinian evolution)
• Insufficient basic knowledge was available to prevent the situation.
• Fund more basic research to fill fundamental gaps in our understanding of life.
• Viruses are a fundamental part of ecosystems. Some are bad, some are good (bacteriophages), all are part of a complex system
• We can’t live without viruses.