Experimental Infection of Mexican Free-Tailed Bats (
            <i>Tadarida brasiliensis</i>
            ) with SARS-CoV-2

Hall, Jeffrey S.; Hofmeister, Erik K.; Ip, Hon S.; Nashold, Sean W.; Leon, Ariel E; Malave, Carly; Falendysz, Elizabeth A.; Rocke, Tonie E.; Carossino, Mariano; Balasuriya, Udeni B. R.; Knowles, Susan

doi:10.1128/msphere.00263-22

Cited by 9 publications

(11 citation statements)

References 21 publications

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“…More recently, two studies looking at the susceptibility of the Brazilian free-tailed bat showed that the species can become infected (without showing symptoms) and develop antibodies to SC2. However, both studies found no evidence of viral transmission to uninfected bats (26,27). Our results correlate with these findings as the Brazilian free-tailed bat ACE2 cell line was able to replicate all three variants of SC2 (Figures 3-5).…”

Section: Discussionsupporting

confidence: 88%

“…Recent studies have shown that bat-borne SC2-like viruses circulate in Rhinolophus species in Southeast Asia, but a direct progenitor virus has yet to be found (25). To date, only four bat species have been experimentally infected with SC2, whereas roughly 1400 species of bats are estimated worldwide (26)(27)(28)(29). To test susceptibility of every bat species to SC2 would be impractical, but less intrusive and lower-cost methods are available to examine if the virus can replicate within a bat species.…”

Section: Introductionmentioning

confidence: 99%

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SARS-CoV-2 utilization of ACE2 from different bat species allows for virus entry and replicationin vitro

Briggs

Sweeney

Blehert

et al. 2023

Preprint

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Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) is believed to have a zoonotic origin. Bats are a suspected natural host of SARS-CoV-2 because of sequence homology with other bat coronaviruses. Understanding the origin of the virus and determining species susceptibility is essential for managing the transmission potential during a pandemic. In a previous study, we established an in vitro animal model of SARS-CoV-2 susceptibility and replication in a non-permissive avian fibroblast cell line (DF1) based on expression of angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) from different animal species. In this work, we express the ACE2 of seven bat species in DF1 cells and determine their ability to support attachment and replication of the original SARS-CoV-2 Wuhan lineage virus, as well as two variants, Delta and Lambda. We demonstrate that the ACE2 receptor of all seven species: little brown bat (Myotis lucifugus), great roundleaf bat (Hipposideros armiger), Pearson's horseshoe bat (Rhinolophus pearsonii), greater horseshoe bat (Rhinolophus ferrumequinum), Brazilian free-tailed bat (Tadarida brasiliensis), Egyptian rousette (Rousettus aegyptiacus), and Chinese rufous horseshoe bat (Rhinolophus sinicus), made the DF1 cells permissible to the three isolates of SARS-CoV-2. However, the level of virus replication differed between bat species and variant tested. In addition, the Wuhan lineage SARS-CoV-2 virus replicated to higher titers (104.5 -105.5 TCID50) than either variant virus (103.5-104.5 TCID50) on pass 1. Interestingly, all viruses tested grew to higher titers (approximately 106 TCID50) when cells expressed the human ACE2 gene compared to bat ACE2. This study provides a practical in vitro method for further testing of animal species for potential susceptibility to current and emerging SARS-CoV-2 viruses.

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Section: Discussionsupporting

confidence: 88%

Section: Introductionmentioning

confidence: 99%

SARS-CoV-2 utilization of ACE2 from different bat species allows for virus entry and replicationin vitro

Briggs

Sweeney

Blehert

et al. 2023

Preprint

View full text Add to dashboard Cite

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“…An experimental challenge of Egyptian fruit bats led to a limited infection without visible signs of disease, but with detectable virus in several tissues, including lungs and lymph nodes, and transmission to one contact bat (28). Challenge of big brown bats did not lead to infection (29); however, two studies of Mexican/Brazilian free-tail bats were contradictory, with one suggesting they were susceptible but not the other (30, 31). ACE2 residues that are thought to be important in SARS-CoV-2 spike binding (38, 39) are more conserved in Egyptian fruit bats (16/20 residues with human), substantially less in big brown bats and Mexican/Brazilian free-tailed bats (11/20 residues), with Jamaican fruit bats intermediate (13/20 residues) (Supplemental Table 1).…”

Section: Discussionmentioning

confidence: 99%

“…Thus, insectivorous bats are typically captured and used for one-off experimental infection studies. Despite these limitations, previous work using Egyptian fruit bats ( Rousettus aegyptiacus ), and insectivorous big brown ( Eptesicus fuscus ) and Brazilian/Mexican free-tailed ( Tadarida brasiliensis ) bats have examined susceptibility to SARS-CoV-2 infections (28–31). Although Egyptian fruit bats were moderately susceptible without disease, with detection of virus in the respiratory tract for several days and transmission to one other bat, big brown bats were not susceptible.…”

Section: Introductionmentioning

confidence: 99%

“…Although Egyptian fruit bats were moderately susceptible without disease, with detection of virus in the respiratory tract for several days and transmission to one other bat, big brown bats were not susceptible. There is conflicting evidence of susceptibility of Brazilian free-tailed bats; one study suggested they are not susceptible (30), whereas another suggested low susceptibility (31). Thus, it is clear host specificity of SARS-CoV-2 infection cannot be determined simply by taxonomic assignment of a given mammalian species.…”

Section: Introductionmentioning

confidence: 99%

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Regulatory T Cell-like Response to SARS-CoV-2 in Jamaican Fruit Bats (Artibeus jamaicensis) Transduced with Human ACE2

Burke

Rocha

Zhan

et al. 2023

Preprint

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Insectivorous Old World horseshoe bats (Rhinolophus spp.) are the likely source of the ancestral SARS-CoV-2 prior to its spillover into humans and causing the COVID-19 pandemic. Natural coronavirus infections of bats appear to be principally confined to the intestines, suggesting fecal-oral transmission; however, little is known about the biology of SARS-related coronaviruses in bats. Previous experimental challenges of Egyptian fruit bats (Rousettus aegyptiacus) resulted in limited infection restricted to the respiratory tract, whereas insectivorous North American big brown bats (Eptesicus fuscus) showed no evidence of infection. In the present study, we challenged Jamaican fruit bats (Artibeus jamaicensis) with SARS-CoV-2 to determine their susceptibility. Infection was confined to the intestine for only a few days with prominent viral nucleocapsid antigen in epithelial cells, and mononuclear cells of the lamina propria and Peyers patches, but with no evidence of infection of other tissues; none of the bats showed visible signs of disease or seroconverted. Expression levels of ACE2 were low in the lungs, which may account for the lack of pulmonary infection. Bats were then intranasally inoculated with a replication-defective adenovirus encoding human ACE2 and 5 days later challenged with SARS-CoV-2. Viral antigen was prominent in lungs for up to 14 days, with loss of pulmonary cellularity during this time; however, the bats did not exhibit weight loss or visible signs of disease. From day 7, bats had low to moderate IgG antibody titers to spike protein by ELISA, and one bat on day 10 had low-titer neutralizing antibodies by a VSV pseudotyped virus assay. CD4+ helper T cells became activated upon ex vivo recall stimulation with SARS-CoV-2 nucleocapsid peptides and exhibited elevated mRNA expression of the regulatory T cell cytokines interleukin-10 and transforming growth factor beta, which may have limited inflammatory pathology. Collectively, these data show that Jamaican fruit bats are of low susceptibility to SARS-CoV-2 but that expression of human ACE2 in their lungs leads to robust infection and an adaptive immune response with low-titer antibodies and a regulatory T cell-like response that may explain the lack of prominent inflammation in the lungs. This model will allow for insights of how SARS-CoV-2 infects bats and how bat innate and adaptive immune responses engage the virus without overt clinical disease.

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The reverse zoonotic potential of SARS-CoV-2

Milich,

Morse

2024

Heliyon

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Experimental Infection of Mexican Free-Tailed Bats ( Tadarida brasiliensis ) with SARS-CoV-2

Cited by 9 publications

References 21 publications

SARS-CoV-2 utilization of ACE2 from different bat species allows for virus entry and replicationin vitro

SARS-CoV-2 utilization of ACE2 from different bat species allows for virus entry and replicationin vitro

Regulatory T Cell-like Response to SARS-CoV-2 in Jamaican Fruit Bats (Artibeus jamaicensis) Transduced with Human ACE2

The reverse zoonotic potential of SARS-CoV-2

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