SARS-CoV-2 replicates in respiratory ex vivo organ cultures of domestic ruminant species

Teodoro, Giovanni Di; Valleriani, Fabrizia; Puglia, Ilaria; Monaco, Federica; Pancrazio, Chiara Di; Luciani, Mirella; Krasteva, Ivanka; Petrini, Antonio; Marcacci, Maurilia; D’Alterio, Nicola; Curini, Valentina; Iorio, Mariangela; Migliorati, Giacomo; Domenico, Marco Di; Morelli, Daniela; Calistri, Paolo; Savini, Giovanni; Decaro, Nicola; Holmes, Edward C.; Lorusso, Alessio

doi:10.1016/j.vetmic.2020.108933

Cited by 49 publications

(76 citation statements)

References 38 publications

(29 reference statements)

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“…Di Teodoro et al also reported an association of SARS-CoV-2 replication with ACE2-expression in cells of the respiratory tract. The ACE2 labeling in the ex vivo tracheal and lung cultures was stronger [ 31 ] than what we observed directly in the lung of the calves in the current study. In the current study, the kidney presented the greatest expression of ACE2, followed by the sparse labeling in the turbinates and tonsil, with the lung only having minimal ACE2 expression when compared to the other tissues.…”

Section: Discussioncontrasting

confidence: 64%

“…Interestingly, while results here and those previously reported by Ulrich and collaborators [ 26 ] suggest lack of SARS-CoV-2 replication, a study utilizing ex vivo tracheal and lung organ explants of domestic ruminants supported sustained viral replication of SARS-CoV-2 [ 31 ]. Di Teodoro et al also reported an association of SARS-CoV-2 replication with ACE2-expression in cells of the respiratory tract.…”

Section: Discussionsupporting

confidence: 58%

“…Initial in vivo studies utilizing intranasal inoculation in cattle suggested a lack of sustained viral replication, as evidenced mostly by lack of viral detection by RT-PCR with only a few samples from two animals being detected over the course of the study [ 26 ]. Although, ex vivo organ cultures from ruminants have been shown susceptible, demonstrating sustained viral replication and an association of SARS-CoV-2 with ACE2-expressing cells [ 31 ]. Interestingly, the distribution of the ACE2 receptor in cattle has been reported to be higher in the liver and kidney, with the lung only having moderate ACE2 receptor expression compared to other tissues [ 32 ].…”

Section: Introductionmentioning

confidence: 99%

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Experimental Inoculation of Young Calves with SARS-CoV-2

Falkenberg

Buckley

Laverack

et al. 2021

Viruses

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The host range of SARS-CoV-2 and the susceptibility of animal species to the virus are topics of great interest to the international scientific community. The angiotensin I converting enzyme 2 (ACE2) protein is the major receptor for the virus, and sequence and structural analysis of the protein has been performed to determine its cross-species conservation. Based on these analyses, cattle have been implicated as a potential susceptible species to SARS-CoV-2 and have been reported to have increased ACE2 receptor distribution in the liver and kidney, and lower levels in the lungs. The goal of the current study was to determine the susceptibility of cattle to SARS-CoV-2 utilizing inoculation routes that facilitated exposure to tissues with increased ACE2 receptor distribution. For this, colostrum-deprived calves approximately 6 weeks of age were inoculated via the intratracheal or intravenous routes. Nasal and rectal swab samples, as well as blood and urine samples, were collected over the course of the study to evaluate viral shedding, viremia, and seroconversion. Pyrexia was used as the primary criteria for euthanasia and tissue samples were collected during necropsy. Importantly, SARS-CoV-2 RNA was detected in only two nasal swab samples collected on days 3 and 10 post-inoculation (pi) in two calves; one calf in the intratracheal group and the other calf in the intravenous group, respectively. Additionally, the calf in the intratracheal group that was positive on the nasal swab on day 3 pi also had a positive tracheobronchial lymph node on day 9 pi. Viral nucleic acid load on these samples, based on PCR cycle threshold values, were low and infectious virus was not recovered from the samples. These results suggest that there was no productive replication of SARS-CoV-2 in calves following intratracheal and intravenous inoculation.

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Section: Discussioncontrasting

confidence: 64%

Section: Discussionsupporting

confidence: 58%

Section: Introductionmentioning

confidence: 99%

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Experimental Inoculation of Young Calves with SARS-CoV-2

Falkenberg

Buckley

Laverack

et al. 2021

Viruses

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“…Defined as enzootic, for a long time, some of these viruses have crossed the animal-human barrier becoming zoonotic ( Chan et al, 2013b ), due to their ability to mutate and recombine adapting that way to new host range ( Li, 2016 ). It is widely recognized that animals were the spillover source for SARS-CoV-2 infection in men ( Schmiege et al, 2020 ; Di Teodoro et al, 2020 ). To deepen the link among animal-men-SARS-COV-2, the susceptibility of many animals to the virus has been investigated and it has been shown that animals such as cats, ferrets and minks are susceptible to the infection, while chickens and pigs are not; interestingly, respiratory ex-vivo organ cultures of cattle and sheep further suggested that also these animal species may be susceptible to the infection ( Di Teodoro et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

“…It is widely recognized that animals were the spillover source for SARS-CoV-2 infection in men ( Schmiege et al, 2020 ; Di Teodoro et al, 2020 ). To deepen the link among animal-men-SARS-COV-2, the susceptibility of many animals to the virus has been investigated and it has been shown that animals such as cats, ferrets and minks are susceptible to the infection, while chickens and pigs are not; interestingly, respiratory ex-vivo organ cultures of cattle and sheep further suggested that also these animal species may be susceptible to the infection ( Di Teodoro et al, 2020 ). Much information is available in veterinary medicine on animal coronaviruses, so that such knowledge may be of help also in human medicine to better understand how the virus behaves and how to face it.…”

Section: Introductionmentioning

confidence: 99%

Therapeutic approaches to coronavirus infection according to “One Health” concept

Rossi

Galosi

Gavazza

et al. 2021

Research in Veterinary Science

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Coronaviridae constantly infect human and animals causing respiratory, gastroenteric or systemic diseases. Over time, these viruses have shown a marked ability to mutate, jumping over the human-animal barrier, thus becoming from enzootic to zoonotic. In the last years, numerous therapeutic protocols have been developed, mainly for severe acute respiratory syndromes in humans. The aim of this review is to summarize drugs or other approaches used in coronavirus infections focusing on different roles of these molecules or bacterial products on viral adhesion and replication or in modulating the host's immune system. Within the “ One Health ” concept, the study of viral pathogenic role and possible therapeutic approaches in both humans and animals is essential to protect public health.

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Animal Models for Studying COVID-19 Pathology and Infection

Yadav

Kenney

2022

Springer Protocols Handbooks

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SARS-CoV-2 replicates in respiratory ex vivo organ cultures of domestic ruminant species

Cited by 49 publications

References 38 publications

Experimental Inoculation of Young Calves with SARS-CoV-2

Experimental Inoculation of Young Calves with SARS-CoV-2

Therapeutic approaches to coronavirus infection according to “One Health” concept

Animal Models for Studying COVID-19 Pathology and Infection

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