A SARS-CoV-2-Related Virus from Malayan Pangolin Causes Lung Infection without Severe Disease in Human ACE2-Transgenic Mice

Liu, Meiqin; Lin, Haofeng; Li, Jing; Chen, Ying; Luo, Yun; Zhang, Wei; Hu, Ben; Tian, Fubo; Hu, Yunjia; Liu, Yujie; Jiang, Ren-Di; Gong, Qian-Chun; Li, Ang; Guo, Zi-Shuo; Li, Bei; Yang, Xing‐Lou; Tong, Yigang; Z, Shi

doi:10.1128/jvi.01719-22

Cited by 15 publications

(21 citation statements)

References 42 publications

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“…Well-studied mammalian hosts, such as humans and domestic dogs, have multiple coronaviruses of several different subfamilies, although most of those of concern in mammals are members of the genera Alphacoronavirus and Betacoronavirus [2]. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is thought to have arisen via a spillover from horseshoe bats (the natural hosts of the Betacoronavirus subgenus sarbecoviruses), with human infection probably via a 'liaison host' such as the raccoon dog (Nyctereutes procyonoides) or Malayan pangolin (Manis javanica) [3][4][5].…”

Section: Introductionmentioning

confidence: 99%

Lack of detection of SARS-CoV-2 in British wildlife 2020–21 and first description of a stoat (Mustela erminea) Minacovirus

Apaa,

Withers,

Mackenzie

et al. 2023

Journal of General Virology

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Repeat spillover of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into new hosts has highlighted the critical role of cross-species transmission of coronaviruses and establishment of new reservoirs of virus in pandemic and epizootic spread of coronaviruses. Species particularly susceptible to SARS-CoV-2 spillover include Mustelidae (mink, ferrets and related animals), cricetid rodents (hamsters and related animals), felids (domestic cats and related animals) and white-tailed deer. These predispositions led us to screen British wildlife with sarbecovirus-specific quantitative PCR and pan coronavirus PCR assays for SARS-CoV-2 using samples collected during the human pandemic to establish if widespread spillover was occurring. Fourteen wildlife species (n=402) were tested, including: two red foxes (Vulpes vulpes), 101 badgers (Meles meles), two wild American mink (Neogale vison), 41 pine marten (Martes martes), two weasels (Mustela nivalis), seven stoats (Mustela erminea), 108 water voles (Arvicola amphibius), 39 bank voles (Myodes glareolous), 10 field voles (Microtus agrestis), 15 wood mice (Apodemus sylvaticus), one common shrew (Sorex aranaeus), two pygmy shrews (Sorex minutus), two hedgehogs (Erinaceus europaeus) and 75 Eurasian otters (Lutra lutra). No cases of SARS-CoV-2 were detected in any animals, but a novel minacovirus related to mink and ferret alphacoronaviruses was detected in stoats recently introduced to the Orkney Islands. This group of viruses is of interest due to pathogenicity in ferrets. The impact of this virus on the health of stoat populations remains to be established.

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Section: Introductionmentioning

confidence: 99%

Lack of detection of SARS-CoV-2 in British wildlife 2020–21 and first description of a stoat (Mustela erminea) Minacovirus

Apaa,

Withers,

Mackenzie

et al. 2023

Journal of General Virology

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“…On the basis of published sequences ( 14 ), we recovered a wild-type BtCoV-422 recombinant virus and two reporter viruses, BtCoV-422-GFP and BtCoV-422-nLuc, using reverse genetics. The synthetic recovery of a single, targeted wild-type virus from published full-length RNA sequencing datasets at biosafety level 3 (BSL-3) (a single isolate among many in a sample) is inherently safer than traditional untargeted culture-based approaches using pooled specimens derived from multiple sources, oftentimes under BSL-2 conditions ( 41 – 44 ). BtCoV-422 replicated efficiently in primary human nonciliated distal airway cells such as LAEs, as well as MVEs and fibroblast cells, but replicated less efficiently than MERS-CoV in primary proximal human airway cells derived from the nasal epithelia of a subset of donors.…”

Section: Discussionmentioning

confidence: 99%

A MERS-CoV antibody neutralizes a pre-emerging group 2c bat coronavirus

Tse,

Hou,

McFadden

et al. 2023

Sci. Transl. Med.

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The repeated emergence of zoonotic human betacoronaviruses (β-CoVs) dictates the need for broad therapeutics and conserved epitope targets for countermeasure design. Middle East respiratory syndrome (MERS)–related coronaviruses (CoVs) remain a pressing concern for global health preparedness. Using metagenomic sequence data and CoV reverse genetics, we recovered a full-length wild-type MERS-like BtCoV/ li /GD/2014-422 (BtCoV-422) recombinant virus, as well as two reporter viruses, and evaluated their human emergence potential and susceptibility to currently available countermeasures. Similar to MERS-CoV, BtCoV-422 efficiently used human and other mammalian dipeptidyl peptidase protein 4 (DPP4) proteins as entry receptors and an alternative DPP4-independent infection route in the presence of exogenous proteases. BtCoV-422 also replicated efficiently in primary human airway, lung endothelial, and fibroblast cells, although less efficiently than MERS-CoV. However, BtCoV-422 shows minor signs of infection in 288/330 human DPP4 transgenic mice. Several broad CoV antivirals, including nucleoside analogs and 3C-like/M pro protease inhibitors, demonstrated potent inhibition against BtCoV-422 in vitro. Serum from mice that received a MERS-CoV mRNA vaccine showed reduced neutralizing activity against BtCoV-422. Although most MERS-CoV–neutralizing monoclonal antibodies (mAbs) had limited activity, one anti-MERS receptor binding domain mAb, JC57-11, neutralized BtCoV-422 potently. A cryo–electron microscopy structure of JC57-11 in complex with BtCoV-422 spike protein revealed the mechanism of cross-neutralization involving occlusion of the DPP4 binding site, highlighting its potential as a broadly neutralizing mAb for group 2c CoVs that use DPP4 as a receptor. These studies provide critical insights into MERS-like CoVs and provide candidates for countermeasure development.

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“…In comparison to the initial lung–intestine mixed sample (GX/P2V/2017), this GX_P2V strain acquired two genomic mutations: an alanine to valine substitution in the nucleoprotein and a 104‐nucleotide deletion in the hypervariable region of the 3′‐terminus untranslated region 7 . This GX_P2V strain is highly attenuated in in vitro and in vivo infection models, permitting cultivation in a biosafety level 2 laboratory 7,8 …”

Section: Methodsmentioning

confidence: 99%

Omicron breakthrough infections in wild‐type SARS‐CoV‐2 vaccinees elicit high levels of neutralizing antibodies against pangolin coronavirus GX_P2V

Luo

Bai

et al. 2023

Journal of Medical Virology

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Omicron BF.7 became the predominant SARS‐CoV‐2 variant in Beijing after the abolishment of Zero‐COVID policy in December 2022. The ability of antibodies elicited by BF.7 infection to cross‐react with SARS‐CoV‐2‐like viruses is unknown. This study aimed to investigate the cross‐reactive neutralizing antibodies against SARS‐CoV‐2‐related pangolin coronavirus GX_P2V in sera from vaccinated and/or SARS‐CoV‐2‐infected individuals. All vaccinated individuals who recovered from Omicron BF.7 breakthrough infections exhibited substantially higher levels of neutralizing antibodies against GX_P2V, compared to other subject groups, with a geometric mean titer (GMT) of 362. Uninfected individuals who received four‐mixed‐dose vaccines also demonstrated higher levels of neutralizing antibodies (GMT = 44) against GX_P2V than those uninfected individuals who received two‐ or three‐dose vaccines and those unvaccinated convalescents of wild‐type SARS‐CoV‐2. This study highlights the significance of prior vaccinations with wild‐type SARS‐CoV‐2 vaccines in generating potent cross‐protective immunity against future spillovers of SARS‐CoV‐2‐like viruses.

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A SARS-CoV-2-Related Virus from Malayan Pangolin Causes Lung Infection without Severe Disease in Human ACE2-Transgenic Mice

Abstract: SARS-CoV-2, which likely spilled over from wildlife, is the third highly pathogenic human coronavirus. Being highly transmissible, it is perpetuating a pandemic and continuously posing a severe threat to global public health.

Cited by 15 publications

References 42 publications

Lack of detection of SARS-CoV-2 in British wildlife 2020–21 and first description of a stoat (Mustela erminea) Minacovirus

Lack of detection of SARS-CoV-2 in British wildlife 2020–21 and first description of a stoat (Mustela erminea) Minacovirus

A MERS-CoV antibody neutralizes a pre-emerging group 2c bat coronavirus

Omicron breakthrough infections in wild‐type SARS‐CoV‐2 vaccinees elicit high levels of neutralizing antibodies against pangolin coronavirus GX_P2V

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