Establishment of an African green monkey model for COVID-19 and protection against re-infection

Woolsey, Courtney; Borisevich, Viktoriya; Prasad, Abhishek N.; Agans, Krystle N.; Deer, Daniel J.; Dobias, Natalie S.; Heymann, John C; Foster, Stephanie L.; Levine, Corri B.; Medina, Liana; Melody, Kevin; Geisbert, Joan B.; Fenton, Karla A.; Geisbert, Thomas W.; Cross, Robert W.

doi:10.1038/s41590-020-00835-8

Cited by 170 publications

(179 citation statements)

References 48 publications

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“…Using traditional virological methods as well as scRNA-Seq, we have begun to parse out the infection dynamics which occur as the disease progresses and virus is eventually cleared in the African green monkey model of mild COVID-19. These findings are consistent with other studies done in African green monkeys (11,12), which share a similar disease pathology to that seen with rhesus macaques (20) and cynomolgus macaques (21). In all cases, the animals display mild disease signs leading to clearance of the virus and recovery.…”

Section: Discussionsupporting

confidence: 92%

“…African green monkeys are a commonly used non-human primate model for studies of respiratory viruses, including SARS-CoV (10). Recently, two studies showed that inoculation of African green monkeys with SARS-CoV-2 results in mild respiratory disease with virus detected in the upper and lower respiratory tract, suggesting that African green monkeys are a suitable nonhuman primate disease model to study SARS-CoV-2 infection and host response dynamics (11,12).…”

Section: Introductionmentioning

confidence: 99%

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Single-cell RNA sequencing reveals SARS-CoV-2 infection dynamics in lungs of African green monkeys

et al. 2021

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Detailed knowledge about the dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is important for uncovering the viral and host factors that contribute to coronavirus disease 2019 (COVID-19) pathogenesis. Old-World nonhuman primates recapitulate mild to moderate cases of COVID-19, thereby serving as important pathogenesis models. We compared African green monkeys inoculated with infectious SARS-CoV-2 or irradiated, inactivated virus to study the dynamics of virus replication throughout the respiratory tract. Genomic RNA from the animals inoculated with the irradiated virus was found to be highly stable, whereas subgenomic RNA, an indicator of viral replication, was found to degrade quickly. We combined this information with single-cell RNA sequencing of cells isolated from the lung and lung-draining mediastinal lymph nodes and developed new analysis methods for unbiased targeting of important cells in the host response to SARS-CoV-2 infection. Through detection of reads to the viral genome, we were able to determine that replication of the virus in the lungs appeared to occur mainly in pneumocytes, whereas macrophages drove the inflammatory response. Monocyte-derived macrophages recruited to the lungs, rather than tissue-resident alveolar macrophages, were most likely to be responsible for phagocytosis of infected cells and cellular debris early in infection, with their roles switching during clearance of infection. Together, our dataset provides a detailed view of the dynamics of virus replication and host responses over the course of mild COVID-19 and serves as a valuable resource to identify therapeutic targets.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Single-cell RNA sequencing reveals SARS-CoV-2 infection dynamics in lungs of African green monkeys

et al. 2021

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“…Non-human primates have been linked to the transmission of many infectious diseases in human populations such as human immunodeficiency virus (HIV), herpes B virus, monkeypox, yellow fever, and Ebola [248,249]. To date, SARS-CoV-2 experimental studies have been reported in rhesus macaques (Macaca mulatta) [250][251][252], cynomolgus macaques (Macaca fascicularis) [253], and green monkeys (Chlorocebus sabaeus) [254]. Regarding experimental studies with SARS-CoV, green monkeys, common marmosets (Callithrix jacchus), squirrel monkeys (Saimiri spp.…”

Section: Non-human Primatesmentioning

confidence: 99%

Host Diversity and Potential Transmission Pathways of SARS-CoV-2 at the Human-Animal Interface

Hedman¹,

Krawczyk

Helmy

et al. 2021

Pathogens

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Emerging infectious diseases present great risks to public health. The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing coronavirus disease 2019 (COVID-19), has become an urgent public health issue of global concern. It is speculated that the virus first emerged through a zoonotic spillover. Basic research studies have suggested that bats are likely the ancestral reservoir host. Nonetheless, the evolutionary history and host susceptibility of SARS-CoV-2 remains unclear as a multitude of animals has been proposed as potential intermediate or dead-end hosts. SARS-CoV-2 has been isolated from domestic animals, both companion and livestock, as well as in captive wildlife that were in close contact with human COVID-19 cases. Currently, domestic mink is the only known animal that is susceptible to a natural infection, develop severe illness, and can also transmit SARS-CoV-2 to other minks and humans. To improve foundational knowledge of SARS-CoV-2, we are conducting a synthesis review of its host diversity and transmission pathways. To mitigate this COVID-19 pandemic, we strongly advocate for a systems-oriented scientific approach that comprehensively evaluates the transmission of SARS-CoV-2 at the human and animal interface.

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“…Such studies demonstrate susceptibility to SARS-CoV-2, albeit with varying levels of viral replication and shedding, in domestic cats (Felis catus) and dogs (Canis lupus familiaris), ferrets (Mustela putorius furo), Syrian hamsters (Mesocricetus auratus), rhesus macaques (Macaca mulatta), cynomolgus macaques (M. fascicularis), African green monkeys (Chlorocebus sp. ), Chinese tree shrews (Tupaia belangeri chinensis), common marmosets (Callithrix jacchus), Egyptian fruit bats (Rousettus aegyptiacus), racoon dogs (Nyctereutes procyonoides) and laboratory rabbits (Oryctolagus cuniculus) [19,27,28,29,30,31,32,33,34,35]. However, experimental studies are models of disease dynamics and do not precisely mimic the dynamics of infection and onward transmission under natural conditions.…”

Section: Host Susceptibilitymentioning

confidence: 99%

“…Captive and wild great apes (Hominidae) are highly susceptible to viral pathogens of humans [80,81] with respiratory infections of human origin [82,83] causing disease that poses a significant and growing threat to the conservation of wild populations across Sub-Saharan Africa [80]. Furthermore, the characteristics of ACE2 predict high susceptibility to SARS-CoV-2 amongst primates, particularly Old-World species [22] and this is borne out by the results of experimental studies [28,31,33].…”

Section: Great Apesmentioning

confidence: 99%

Assessing the Risks of SARS-CoV-2 in Wildlife

Delahay¹,

Fuente²,

Smith³

et al. 2020

Preprint

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The novel coronavirus SARS-CoV-2 likely emerged from a wildlife source with transmission to humans followed by rapid geographic spread throughout the globe and dramatic impacts on both human health and global economies. Since the onset of the pandemic, there have been several instances of human-to-animal transmission involving companion, farmed and zoo animals, with the clear potential for spread into free-living wildlife. The establishment of reservoirs of infection in wild animals would create significant challenges to infection control in humans and could pose a threat to the welfare and conservation status of wildlife. Herein, we discuss the potential for exposure, maintenance and onward transmission of SARS-CoV-2 in an initial selection of wild and feral species (bats, canids, felids, mustelids, great apes). Targeted surveillance and dynamic risk assessment are important tools for the early detection of infection in wildlife and a means of collating and synthesising emerging information in a rapidly changing situation. Such efforts should be integrated with public health information to provide insights into the potential role of wild mammals in the continuing epidemiology of SARS-CoV-2. This approach should also be adopted to address the wider need to proactively assess threats to human and animal health from other diseases that may emerge from wildlife.

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Establishment of an African green monkey model for COVID-19 and protection against re-infection

Cited by 170 publications

References 48 publications

Single-cell RNA sequencing reveals SARS-CoV-2 infection dynamics in lungs of African green monkeys

Single-cell RNA sequencing reveals SARS-CoV-2 infection dynamics in lungs of African green monkeys

Host Diversity and Potential Transmission Pathways of SARS-CoV-2 at the Human-Animal Interface

Assessing the Risks of SARS-CoV-2 in Wildlife

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