Chimeric Porcine Deltacoronaviruses with Sparrow Coronavirus Spike Protein or the Receptor-Binding Domain Infect Pigs but Lose Virulence and Intestinal Tropism.

Xiaoyu Niu,Fanzhi Kong,Yixuan J Hou,Qiuhong Wang,Kwonil Jung,Linda J Saif

doi:10.3390/v13010122

Xiaoyu Niu, Fanzhi Kong + Show 4 more

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https://doi.org/10.3390/v13010122

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Abstract

Porcine deltacoronavirus (PDCoV) strain OH-FD22 infects poultry and shares high nucleotide identity with sparrow-origin deltacoronaviruses (SpDCoV) ISU73347 and HKU17 strains. We hypothesized that the spike (S) protein or receptor-binding domain (RBD) from these SpDCoVs would alter the host and tissue tropism of PDCoV. First, an infectious cDNA clone of PDCoV OH-FD22 strain (icPDCoV) was generated and used to construct chimeric icPDCoVs harboring the S protein of HKU17 (icPDCoV-SHKU17) or the RBD of ISU73347 (icPDCoV-RBDISU). To evaluate their pathogenesis, neonatal gnotobiotic pigs were inoculated orally/oronasally with the recombinant viruses or PDCoV OH-FD22. All pigs inoculated with icPDCoV or OH-FD22 developed severe diarrhea and shed viral RNA at moderate-high levels (7.62–10.56 log10 copies/mL) in feces, and low-moderate levels in nasal swabs (4.92–8.48 log10 copies/mL). No pigs in the icPDCoV-SHKU17 and icPDCoV-RBDISU groups showed clinical signs. Interestingly, low-moderate levels (5.07–7.06 log10 copies/mL) of nasal but not fecal viral RNA shedding were detected transiently at 1–4 days post-inoculation in 40% (2/5) of icPDCoV-SHKU17- and 50% (1/2) of icPDCoV-RBDISU-inoculated pigs. These results confirm that PDCoV infected both the upper respiratory and intestinal tracts of pigs. The chimeric viruses displayed an attenuated phenotype with the loss of tropism for the pig intestine. The SpDCoV S protein and RBD reduced viral replication in pigs, suggesting limited potential for cross-species spillover upon initial passage.

Highlights

The Coronaviridae family is classified into four genera: Alphacoronavirus, Betacoronavirus, Gammacoronavirus, and Deltacoronavirus
Though all three recombinant viruses replicated at a similar rate at the early phase [within 16 h post-inoculation], much lower peak infectious titers were observed for infectious cDNA clone of PDCoV OHFD22 strain (icPDCoV)-SHKU17 and icPDCoV-RBDISU mutants (Figure 3A)
Those two chimeric viruses showed less efficient replication compared with icPDCoV in LLC-PK1 cells

Summary

Introduction

The Coronaviridae family is classified into four genera: Alphacoronavirus, Betacoronavirus, Gammacoronavirus, and Deltacoronavirus These coronaviruses (CoVs) infect various species and cause a broad spectrum of clinical outcomes, from asymptomatic infection to respiratory, gastrointestinal, hepatic, and neurological diseases, and peritonitis. SpDCoV strains were detected from sparrow fecal samples collected from swine farms in the United States [18] and they showed higher sequence identity to PDCoV and HKU17 than to other avian DCoVs, suggesting that there may be an evolutionary association between the SpDCoVs and PDCoV. PDCoV experimentally infected poultry [13] and gnotobiotic calves [23] Both in vitro and in vivo studies suggeste a broad host range of PDCoV

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