Isolation of SARS-CoV-2 B.1.1.28.2 (P2) variant and pathogenicity comparison with D614G variant in hamster model

Yadav, Pragya D; Mohandas, Sreelekshmy; Sarkale, Prasad; Nyayanit, Dimpal A; Shete, Anita M.; Sahay, Rima R.; Potdar, Varsha; Baradkar, Shrikant; Gupta, Nivedita; Sapkal, Gajanan; Abraham, Priya; Panda, Samiran; Bhargava, Balram

doi:10.1016/j.jiph.2021.12.009

Cited by 9 publications

(5 citation statements)

References 27 publications

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“…The attenuation in mice was unexpected given that B.1.1.529 has alterations in the RBD that are sites associated with adaptation for mice 25 – 27 . The attenuation in hamsters seen by our group and others 43 was also surprising, given that other SARS-CoV-2 variants replicate to high levels in this animal 35 , 44 , 45 . Whereas the >30 changes in the B.1.1.529 spike protein could impact receptor engagement, changes in other proteins could affect replication, temperature sensitivity, cell and tissue tropism, and induction of pro-inflammatory responses in a species-specific manner.…”

Section: Discussionmentioning

confidence: 61%

SARS-CoV-2 Omicron virus causes attenuated disease in mice and hamsters

Halfmann

Iida

Iwatsuki‐Horimoto

et al. 2022

Nature

585

110

431

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The recent emergence of B.1.1.529, the Omicron variant1,2, has raised concerns of escape from protection by vaccines and therapeutic antibodies. A key test for potential countermeasures against B.1.1.529 is their activity in preclinical rodent models of respiratory tract disease. Here, using the collaborative network of the SARS-CoV-2 Assessment of Viral Evolution (SAVE) programme of the National Institute of Allergy and Infectious Diseases (NIAID), we evaluated the ability of several B.1.1.529 isolates to cause infection and disease in immunocompetent and human ACE2 (hACE2)-expressing mice and hamsters. Despite modelling data indicating that B.1.1.529 spike can bind more avidly to mouse ACE2 (refs. 3,4), we observed less infection by B.1.1.529 in 129, C57BL/6, BALB/c and K18-hACE2 transgenic mice than by previous SARS-CoV-2 variants, with limited weight loss and lower viral burden in the upper and lower respiratory tracts. In wild-type and hACE2 transgenic hamsters, lung infection, clinical disease and pathology with B.1.1.529 were also milder than with historical isolates or other SARS-CoV-2 variants of concern. Overall, experiments from the SAVE/NIAID network with several B.1.1.529 isolates demonstrate attenuated lung disease in rodents, which parallels preliminary human clinical data.

show abstract

Section: Discussionmentioning

confidence: 61%

SARS-CoV-2 Omicron virus causes attenuated disease in mice and hamsters

Halfmann

Iida

Iwatsuki‐Horimoto

et al. 2022

Nature

585

110

431

View full text Add to dashboard Cite

show abstract

“…The attenuation in mice was unexpected given that B.1.1.529 has multiple mutations in the RBD that are sites (K417, E484, Q493, Q498, and N501) associated with adaptation for mice [23][24][25] . Moreover, the attenuation in hamsters also was surprising, given that all prior SARS-CoV-2 variants have replicated relatively equivalently and to high levels in this animal 35,43,44 . However, our results showing attenuation of B.1.1.529 in hamsters are consistent with another preliminary report 45 .…”

Section: Discussionmentioning

confidence: 99%

The SARS-CoV-2 B.1.1.529 Omicron virus causes attenuated infection and disease in mice and hamsters

Diamond

Halfmann

Maemura³

et al. 2021

Preprint

100

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Despite the development and deployment of antibody and vaccine countermeasures, rapidly-spreading SARS-CoV-2 variants with mutations at key antigenic sites in the spike protein jeopardize their efficacy. The recent emergence of B.1.1.529, the Omicron variant1,2, which has more than 30 mutations in the spike protein, has raised concerns for escape from protection by vaccines and therapeutic antibodies. A key test for potential countermeasures against B.1.1.529 is their activity in pre-clinical rodent models of respiratory tract disease. Here, using the collaborative network of the SARS-CoV-2 Assessment of Viral Evolution (SAVE) program of the National Institute of Allergy and Infectious Diseases (NIAID), we evaluated the ability of multiple B.1.1.529 Omicron isolates to cause infection and disease in immunocompetent and human ACE2 (hACE2) expressing mice and hamsters. Despite modeling and binding data suggesting that B.1.1.529 spike can bind more avidly to murine ACE2, we observed attenuation of infection in 129, C57BL/6, and BALB/c mice as compared with previous SARS-CoV-2 variants, with limited weight loss and lower viral burden in the upper and lower respiratory tracts. Although K18-hACE2 transgenic mice sustained infection in the lungs, these animals did not lose weight. In wild-type and hACE2 transgenic hamsters, lung infection, clinical disease, and pathology with B.1.1.529 also were milder compared to historical isolates or other SARS-CoV-2 variants of concern. Overall, experiments from multiple independent laboratories of the SAVE/NIAID network with several different B.1.1.529 isolates demonstrate attenuated lung disease in rodents, which parallels preliminary human clinical data.

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“…In parasite/viral coinfections, IFN-alpha/beta can modulate IFN-γ, which is required for the clearance of the parasite. A reduction in IFN-γ after an initial viral infection is associated with increased parasite pathology [54]. We observed an increase in systemic IFN-γ, but the effect that IFN-alpha/beta may have on this response is unknown.…”

Section: Discussionmentioning

confidence: 70%

Coccidioides posadasii and SARS-CoV-2 Co-infection in the K18-hACE2 Transgenic Mouse Model

Kollath,

Grill,

Itogawa

et al. 2023

Preprint

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Early reports showed that patients with COVID-19 who had a previous diagnosis of Coccidioidomycosis (Valley fever, VF) who had cleared VF months and years prior had re-emergence of VF after COVID-19. However, total numbers of annual cases reported to CDC did not appear to rise dramatically. We therefore investigated serial infection of Coccidioides posadasii (C.p.) and variants of SARS-CoV2 in an K18-hACE2 transgenic mouse to assess the impact on disease outcomes. We intranasally challenged mice sequentially with sub-lethal doses of 100 plaque forming units (PFUs) per mouse of SARS-CoV-2 (variants WA-1, Delta, Omicron BA1) and 24 hours later with 100 arthroconidia per mouse of a low virulence Coccidioides posadasii strain 1038 and vice versa. Lungs, brain, and spleen were extracted and cultured to assess fungal burden and half of the lung was saved for histopathology. To assess pathogenesis, we repeated experiment but sacrificed a subset of mice on days 1, 3, 5, and 6 post-infections in order to assess viral/fungal burden in the lungs. Serum was collected at each time point to measure differences in systemic cytokine/chemokine responses. Experiments were conducted under IACUC protocol # 21-025 at Northern Arizona University. We examined differences in disease outcome between the co-infected groups and groups that only received a primary infection. Co-infected groups had a more severe disease progression as well as decreased survival. Interestingly, results differed depending on SARS-CoV-2 variant (WA-1, Delta, Omicron), infection timing (CoV2 first, C.p. second or vice versa). The groups that were infected with the virus first had decreased survival, increased morbidity (significant weight loss), and increased fungal and viral burdens. There were also differences in immune responses and number/size of spherules, the virus first groups had an increase in circulating pro-inflammatory cytokines and larger more abundant spherules. This is the first in vivo investigation of a co-infection of SARS-CoV-2 and Coccidioides to date. Because of the increased severity of disease, we contemplate the serious implications to the populations that live in areas of high fungal burden and how the SARS-CoV-2 virus can complicate disease progression.

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Isolation of SARS-CoV-2 B.1.1.28.2 (P2) variant and pathogenicity comparison with D614G variant in hamster model

Cited by 9 publications

References 27 publications

SARS-CoV-2 Omicron virus causes attenuated disease in mice and hamsters

SARS-CoV-2 Omicron virus causes attenuated disease in mice and hamsters

The SARS-CoV-2 B.1.1.529 Omicron virus causes attenuated infection and disease in mice and hamsters

Coccidioides posadasii and SARS-CoV-2 Co-infection in the K18-hACE2 Transgenic Mouse Model

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