Susceptibility of sheep to experimental infection with SARS-CoV-2

Authors: GAUDREAULT, NATASHA - Kansas State University; COOL, KONNER - Kansas State University; TRUJILLO, JESSIE - Kansas State University; MOROZOV, IGOR - Kansas State University; MEEKINS, DAVID - Kansas State University; MCDOWELL, CHESTER - Kansas State University; BOLD, DASHZEVEG - Kansas State University; CAROSSINO, MARINAO - Louisiana State University; Mitzel, Dana; BALARAMAN, VELMURUGAN - Kansas State University; KWON, TAEYONG - Kansas State University; MADDEN, DANIEL - Kansas State University; LIBANORI ARTIAGA, BIANCA - Kansas State University; POGRANICHNIY, ROMAN - Kansas State University; ROMAN-SOSA, GLEYDER - Kansas State University; HENNINGSON, JAMIE - Kansas State University; Wilson, William - Bill; BALASURIYA, UDENI - Louisiana State University; GARCIA-SASTRE, ADOLFO - The Icahn School Of Medicine At Mount Sinai; RICHT, JUERGEN - Kansas State University

Submitted to: Emerging Microbes & Infections
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/29/2022
Publication Date: 2/24/2022
Citation: Gaudreault, N.N., Cool, K., Trujillo, J.D., Morozov, I., Meekins, D.A., McDowell, C., Bold, D., Carossino, M., Mitzel, D.N., Balaraman, V., Kwon, T., Madden, D.W., Libanori Artiaga, B., Pogranichniy, R.M., Roman-Sosa, G., Henningson, J., Wilson, W.C., Balasuriya, U.B., Garcia-Sastre, A., Richt, J.A. 2022. Susceptibility of sheep to experimental infection with SARS-CoV-2. Emerging Microbes & Infections. 11(1):662-675. https://doi.org/10.1080/22221751.2022.2037397.
DOI: https://doi.org/10.1080/22221751.2022.2037397

Interpretive Summary: The COVID-19 global pandemic that has had significant impacts on human health and the economy. SARS-CoV-2 is highly transmittable and the cause of coronavirus 19 disease (COVID-19) in humans. A wide range of animal species have also been shown to be susceptible to virus that causes the disease. Domestic and large cats, mink, ferrets, hamsters, deer mice, white-tailed deer, and non-human primates have been shown to be highly susceptible, whereas other species such as mice, dogs, pigs and cattle appear to be refractory to infection or have very limited susceptibility. Sheep are a commonly farmed domestic ruminant that up until now have not been thoroughly investigated for their susceptibility to the virus. Therefore, we performed in vitro and in vivo studies which consisted of infection of ruminant-derived cell cultures and experimental challenge of sheep to investigate their susceptibility to the virus. Our results showed that sheep-derived cell cultures could support viral replication, while bovine-derived cell lines did not. Furthermore, experimental infection of sheep demonstrated limited infection with viral nucleic acid shedding primarily at 1 day post challenge (DPC). The virus was mainly detected in the respiratory tract and lymphoid tissues at 4 and 8 DPC. The data indicated transmission to co-mingled naïve sheep was not efficient. Furthermore, we used challenge inoculum consisting of a mixture of two SARS-CoV-2 isolates, representatives of the ancestral lineage A and the alpha variant of concern (VOC) B.1.1.7, to study competition of the two virus strains which was determined by next generation sequencing. Our results indicate that the alpha variant replicated in sheep, out-competing the ancestral lineage A strain.

Technical Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for a global pandemic that has had significant impacts on human health and the economy. SARS-CoV-2 is highly transmittable and the cause of coronavirus 19 disease (COVID-19) in humans. A wide range of animal species have also been shown to be susceptible to SARS-CoV-2 infection by either experimental and/or natural infections. Domestic and large cats, mink, ferrets, hamsters, deer mice, white-tailed deer, and non-human primates have been shown to be highly susceptible, whereas other species such as mice, dogs, pigs and cattle appear to be refractory to infection or have very limited susceptibility. Sheep are a commonly farmed domestic ruminant that up until now have not been thoroughly investigated for their susceptibility to SARS-CoV-2. Therefore, we performed in vitro and in vivo studies which consisted of infection of ruminant-derived cell cultures and experimental challenge of sheep to investigate their susceptibility to SARS-CoV-2. Our results showed that sheep-derived cell cultures could support viral replication, while bovine-derived cell lines did not. Furthermore, experimental challenge of sheep demonstrated limited infection with viral RNA shed primarily at 1 day post challenge (DPC), and mainly detected in the respiratory tract and lymphatic tissues at 4 and 8 DPC. Seroreactivity was also observed in some of the principal infected sheep but not the contact sentinels. Together the data indicate transmission to co-mingled naïve sheep was not efficient. Furthermore, we used challenge inoculum consisting of a mixture of two SARS-CoV-2 isolates, representatives of the ancestral lineage A and the alpha variant of concern (VOC) B.1.1.7, to study competition of the two virus strains which was determined by next generation sequencing. Our results indicate that the SARS-CoV-2 alpha variant replicated in sheep, outcompeting the ancestral lineage A strain.