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ACE2 and TMPRSS2 variation in savanna monkeys (Chlorocebus spp.): Potential risk for zoonotic/anthroponotic transmission of SARS-CoV-2 and a potential model for functional studies.
PLoS One. 2020; 15(6):e0235106.Plos

Abstract

The COVID-19 pandemic, caused by the coronavirus SARS-CoV-2, has devastated health infrastructure around the world. Both ACE2 (an entry receptor) and TMPRSS2 (used by the virus for spike protein priming) are key proteins to SARS-CoV-2 cell entry, enabling progression to COVID-19 in humans. Comparative genomic research into critical ACE2 binding sites, associated with the spike receptor binding domain, has suggested that African and Asian primates may also be susceptible to disease from SARS-CoV-2 infection. Savanna monkeys (Chlorocebus spp.) are a widespread non-human primate with well-established potential as a bi-directional zoonotic/anthroponotic agent due to high levels of human interaction throughout their range in sub-Saharan Africa and the Caribbean. To characterize potential functional variation in savanna monkey ACE2 and TMPRSS2, we inspected recently published genomic data from 245 savanna monkeys, including 163 wild monkeys from Africa and the Caribbean and 82 captive monkeys from the Vervet Research Colony (VRC). We found several missense variants. One missense variant in ACE2 (X:14,077,550; Asp30Gly), common in Ch. sabaeus, causes a change in amino acid residue that has been inferred to reduce binding efficiency of SARS-CoV-2, suggesting potentially reduced susceptibility. The remaining populations appear as susceptible as humans, based on these criteria for receptor usage. All missense variants observed in wild Ch. sabaeus populations are also present in the VRC, along with two splice acceptor variants (at X:14,065,076) not observed in the wild sample that are potentially disruptive to ACE2 function. The presence of these variants in the VRC suggests a promising model for SARS-CoV-2 infection and vaccine and therapy development. In keeping with a One Health approach, characterizing actual susceptibility and potential for bi-directional zoonotic/anthroponotic transfer in savanna monkey populations may be an important consideration for controlling COVID-19 epidemics in communities with frequent human/non-human primate interactions that, in many cases, may have limited health infrastructure.

Authors+Show Affiliations

Department of Anthropology, Boston University, Boston, Massachusetts, United States of America.Department of Genetics, Rutgers University, New Brunswick, New Jersey, United States of America.Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior,University of California-Los Angeles, Los Angeles, California, United States of America. Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznan, Poland. Eye on Primates, Los Angeles, California, United States of America.Federal State Institution "National Medical Research Center for Therapy and Preventive Medicine" of the Ministry of Healthcare of the Russian Federation, Moscow, Russia.Division of Medical Virology, National Health Laboratory Service, Bloemfontein, Free State, South Africa. Division of Virology, Faculty of Health Sciences, University of the Free State, Bloemfontein, Free State, South Africa.Department of Biology, University of Antwerp, Antwerp, Belgium. Naturalis Biodiversity Center, Leiden, The Netherlands.Department of Pathology, Section on Comparative Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States of America.Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior,University of California-Los Angeles, Los Angeles, California, United States of America.Department of Genetics, University of the Free State, Bloemfontein, Free State, South Africa.Department of Genetics, University of the Free State, Bloemfontein, Free State, South Africa. Department of Anthropology, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin, United States of America.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32574196

Citation

Schmitt, Christopher A., et al. "ACE2 and TMPRSS2 Variation in Savanna Monkeys (Chlorocebus Spp.): Potential Risk for Zoonotic/anthroponotic Transmission of SARS-CoV-2 and a Potential Model for Functional Studies." PloS One, vol. 15, no. 6, 2020, pp. e0235106.
Schmitt CA, Bergey CM, Jasinska AJ, et al. ACE2 and TMPRSS2 variation in savanna monkeys (Chlorocebus spp.): Potential risk for zoonotic/anthroponotic transmission of SARS-CoV-2 and a potential model for functional studies. PLoS One. 2020;15(6):e0235106.
Schmitt, C. A., Bergey, C. M., Jasinska, A. J., Ramensky, V., Burt, F., Svardal, H., Jorgensen, M. J., Freimer, N. B., Grobler, J. P., & Turner, T. R. (2020). ACE2 and TMPRSS2 variation in savanna monkeys (Chlorocebus spp.): Potential risk for zoonotic/anthroponotic transmission of SARS-CoV-2 and a potential model for functional studies. PloS One, 15(6), e0235106. https://doi.org/10.1371/journal.pone.0235106
Schmitt CA, et al. ACE2 and TMPRSS2 Variation in Savanna Monkeys (Chlorocebus Spp.): Potential Risk for Zoonotic/anthroponotic Transmission of SARS-CoV-2 and a Potential Model for Functional Studies. PLoS One. 2020;15(6):e0235106. PubMed PMID: 32574196.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - ACE2 and TMPRSS2 variation in savanna monkeys (Chlorocebus spp.): Potential risk for zoonotic/anthroponotic transmission of SARS-CoV-2 and a potential model for functional studies. AU - Schmitt,Christopher A, AU - Bergey,Christina M, AU - Jasinska,Anna J, AU - Ramensky,Vasily, AU - Burt,Felicity, AU - Svardal,Hannes, AU - Jorgensen,Matthew J, AU - Freimer,Nelson B, AU - Grobler,J Paul, AU - Turner,Trudy R, Y1 - 2020/06/23/ PY - 2020/05/14/received PY - 2020/06/08/accepted PY - 2020/6/24/entrez PY - 2020/6/24/pubmed PY - 2020/7/1/medline SP - e0235106 EP - e0235106 JF - PloS one JO - PLoS One VL - 15 IS - 6 N2 - The COVID-19 pandemic, caused by the coronavirus SARS-CoV-2, has devastated health infrastructure around the world. Both ACE2 (an entry receptor) and TMPRSS2 (used by the virus for spike protein priming) are key proteins to SARS-CoV-2 cell entry, enabling progression to COVID-19 in humans. Comparative genomic research into critical ACE2 binding sites, associated with the spike receptor binding domain, has suggested that African and Asian primates may also be susceptible to disease from SARS-CoV-2 infection. Savanna monkeys (Chlorocebus spp.) are a widespread non-human primate with well-established potential as a bi-directional zoonotic/anthroponotic agent due to high levels of human interaction throughout their range in sub-Saharan Africa and the Caribbean. To characterize potential functional variation in savanna monkey ACE2 and TMPRSS2, we inspected recently published genomic data from 245 savanna monkeys, including 163 wild monkeys from Africa and the Caribbean and 82 captive monkeys from the Vervet Research Colony (VRC). We found several missense variants. One missense variant in ACE2 (X:14,077,550; Asp30Gly), common in Ch. sabaeus, causes a change in amino acid residue that has been inferred to reduce binding efficiency of SARS-CoV-2, suggesting potentially reduced susceptibility. The remaining populations appear as susceptible as humans, based on these criteria for receptor usage. All missense variants observed in wild Ch. sabaeus populations are also present in the VRC, along with two splice acceptor variants (at X:14,065,076) not observed in the wild sample that are potentially disruptive to ACE2 function. The presence of these variants in the VRC suggests a promising model for SARS-CoV-2 infection and vaccine and therapy development. In keeping with a One Health approach, characterizing actual susceptibility and potential for bi-directional zoonotic/anthroponotic transfer in savanna monkey populations may be an important consideration for controlling COVID-19 epidemics in communities with frequent human/non-human primate interactions that, in many cases, may have limited health infrastructure. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/32574196/ACE2_and_TMPRSS2_variation_in_savanna_monkeys__Chlorocebus_spp__:_Potential_risk_for_zoonotic/anthroponotic_transmission_of_SARS_CoV_2_and_a_potential_model_for_functional_studies_ DB - PRIME DP - Unbound Medicine ER -