Tissue distribution of angiotensin-converting enzyme 2 (ACE2) receptor in wild animals with a focus on artiodactyls, mustelids and phocids

Lean, Fabian Z. X.; Cox, Ruth; Madslien, Knut; Spiro, Simon; Nymo, Ingebjørg Helena; Bröjer, Caroline; Neimanis, Aleksija; Lawson, Becki; Holmes, Paul; Man, Catherine; Folkow, Lars P.; Gough, Julie E.; Ackroyd, Stuart; Evans, Liam; Wrigglesworth, Ethan; Grimholt, Unni; McElhinney, Lorraine M.; Brookes, Sharon M; Delahay, Richard J.; Núñez, Alejandro

doi:10.1016/j.onehlt.2023.100492

Cited by 6 publications

(7 citation statements)

References 67 publications

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“…The present study, together with a recent report demonstrating ACE2 receptor expression in the respiratory tract of several mammalian and deer species, including fallow deer (17) highlights the need for ongoing surveillance particularly as novel VOCs are still emerging (32). (17), whether other receptors, such as TMPRSS2, are also necessary for SARS-CoV-2 infection of fallow deer cells is currently unknown. SARS-CoV-2 in experimentally-infected white-tailed deer, challenged with a human B.1 SARS-CoV-2 isolate, infected epithelial cells in both upper respiratory tract and lung tissue (10).…”

Section: Discussionmentioning

confidence: 56%

“…The majority of surveillance studies investigating the serostatus of deer in Europe have not sampled animals post-2021 and have not studied deer with defined and quantified interactions with humans (15,16). The present study, together with a recent report demonstrating ACE2 receptor expression in the respiratory tract of several mammalian and deer species, including fallow deer (17) highlights the need for ongoing surveillance particularly as novel VOCs are still emerging (32). (17), whether other receptors, such as TMPRSS2, are also necessary for SARS-CoV-2 infection of fallow deer cells is currently unknown.…”

Section: Discussionmentioning

confidence: 83%

“…Interactions of these wild, free-ranging species with humans may be low and therefore there may be limited opportunities for transmission events (15). However, a recent study reported expression of the viral primary receptor, angiotensin-converting enzyme-2 (ACE2), in bronchiolar epithelium of several deer species, including fallow deer, roe deer, red deer and muntjac (Muntiacus reevesi) (17). This raises the possibility that further deer species may be susceptible to SARS-CoV-2 infection, particularly with the emergence of novel, highly-transmissible variants of concern (VOC) in humans which may have expanded host tropism compared to ancestral viruses (18).…”

Section: Introductionmentioning

confidence: 99%

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First Eurasian cases of SARS-CoV-2 seropositivity in a free-ranging urban population of wild fallow deer

Purves

Brown

Haverty

et al. 2023

Preprint

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Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infects wildlife. Recent studies highlighted that variants of concern (VOC) may expand into novel animal reservoirs with the potential for reverse zoonosis. North American white-tailed deer are the only deer species in which SARS-CoV-2 has been documented, raising the question whether further reservoir species exist as new VOC emerge. Here, we report the first cases of deer SARS-CoV-2 seropositivity in Eurasia, in a city population of fallow deer in Dublin, Ireland. Deer were seronegative in 2020 (circulating variant in humans: Alpha), one animal was seropositive in 2021 (Delta variant), and 57% of animals tested in 2022 were seropositive (Omicron variant). Ex vivo, a clinical isolate of Omicron BA.1 infected fallow deer precision cut lung slice type-2 pneumocytes, also a major target of infection in human lungs. Our findings suggest a change in host tropism as new variants emerged in the human reservoir, highlighting the importance of continued wildlife disease monitoring and limiting human-wildlife contacts.

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Section: Discussionmentioning

confidence: 56%

Section: Discussionmentioning

confidence: 83%

Section: Introductionmentioning

confidence: 99%

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First Eurasian cases of SARS-CoV-2 seropositivity in a free-ranging urban population of wild fallow deer

Purves

Brown

Haverty

et al. 2023

Preprint

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“…Hence, our study provides this critical comparative information, contributing to further understanding SARS-CoV-2 pathogenesis and informing on the suitability of these different animal species as models of COVID-19 disease. While recent studies evaluated the distribution of ACE2 in the lung, intestine, and other organs of various animal species including dogs, cats, artiodactyls, mustelids, other zoo species, primates, and phocids ( 49 – 52 ), to our knowledge, no study to date has quantitatively evaluated the expression of both ACE2 and TMPRSS2 comparatively in different species to characterize their distribution throughout the different segments of the respiratory tract. In addition, these previous studies have used cross-reactive anti-human ACE2 antibodies for staining tissues from different animal species; such antibodies have been suboptimal in their performance for tissue immunostaining in non-human mammalian species, often yielding non-specific binding and high levels of background in the author’s experience.…”

Section: Discussionmentioning

confidence: 99%

“…An additional study in rats has shown a similar distribution of the rat ACE2 and TMPRSS2 proteins within the nasal cavity, trachea, bronchioles, and alveoli ( 49 ). Recently, the tissue distribution of the ACE2 receptor has been evaluated via immunohistochemistry (IHC) in the lung and intestine of various animal species including dogs, cats, pigs, rats, several artiodactyls, mustelids, other zoo species and primates, as well as phocids ( 49 – 52 ). These studies have made use of cross-reactive ACE2 antibodies and showed ACE2 expression in bronchiolar epithelia and occasionally AT1 cells, blood vessels, and enterocytes in some but not all species examined.…”

Section: Introductionmentioning

confidence: 99%

ACE2 and TMPRSS2 distribution in the respiratory tract of different animal species and its correlation with SARS-CoV-2 tissue tropism

Carossino,

Izadmehr,

Trujillo

et al. 2024

Microbiol Spectr

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A wide range of animal species show variable susceptibility to SARS-CoV-2; however, host factors associated with varied susceptibility remain to be defined. Here, we examined whether susceptibility to SARS-CoV-2 and virus tropism in different animal species are dependent on the expression and distribution of the virus receptor angiotensin-converting enzyme 2 ( ACE2 ) and the host cell factor transmembrane serine protease 2 ( TMPRSS2 ). We cataloged the upper and lower respiratory tract of multiple animal species and humans in a tissue-specific manner and quantitatively evaluated the distribution and abundance of ACE2 and TMPRSS2 mRNA in situ . Our results show that: (i) ACE2 and TMPRSS2 mRNA are abundant in the conduction portion of the respiratory tract, (ii) ACE2 mRNA occurs at a lower abundance compared to TMPRSS2 mRNA, (iii) co-expression of ACE2-TMPRSS2 mRNAs is highest in those species with the highest susceptibility to SARS-CoV-2 infection (i.e., cats, Syrian hamsters, and white-tailed deer), and (iv) expression of ACE2 and TMPRSS2 mRNA was not altered following SARS-CoV-2 infection. Our results demonstrate that while specific regions of the respiratory tract are enriched in ACE2 and TMPRSS2 mRNAs in different animal species, this is only a partial determinant of susceptibility to SARS-CoV-2 infection. IMPORTANCE SARS-CoV-2 infects a wide array of domestic and wild animals, raising concerns regarding its evolutionary dynamics in animals and potential for spillback transmission of emerging variants to humans. Hence, SARS-CoV-2 infection in animals has significant public health relevance. Host factors determining animal susceptibility to SARS-CoV-2 are vastly unknown, and their characterization is critical to further understand susceptibility and viral dynamics in animal populations and anticipate potential spillback transmission. Here, we quantitatively assessed the distribution and abundance of the two most important host factors, angiotensin-converting enzyme 2 and transmembrane serine protease 2, in the respiratory tract of various animal species and humans. Our results demonstrate that while specific regions of the respiratory tract are enriched in these two host factors, they are only partial determinants of susceptibility. Detailed analysis of additional host factors is critical for our understanding of the underlying mechanisms governing viral susceptibility and reservoir hosts.

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Natural SARS-CoV-2 infection in dogs: Determination of viral loads, distributions, localizations, and pathology

Piewbang,

Poonsin,

Lohavicharn

et al. 2024

Acta Tropica

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Tissue distribution of angiotensin-converting enzyme 2 (ACE2) receptor in wild animals with a focus on artiodactyls, mustelids and phocids

Cited by 6 publications

References 67 publications

First Eurasian cases of SARS-CoV-2 seropositivity in a free-ranging urban population of wild fallow deer

First Eurasian cases of SARS-CoV-2 seropositivity in a free-ranging urban population of wild fallow deer

ACE2 and TMPRSS2 distribution in the respiratory tract of different animal species and its correlation with SARS-CoV-2 tissue tropism

Natural SARS-CoV-2 infection in dogs: Determination of viral loads, distributions, localizations, and pathology

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