Animal Coronavirus Pathogenesis and Immunity

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Animal Viruses".

Deadline for manuscript submissions: closed (31 May 2022) | Viewed by 29322

Special Issue Editor

College of Veterinary Medicine, China Agricultural University, Beijing, China.
Interests: Coronavirus in animals

Special Issue Information

Dear Colleagues,

Coronaviruses, a large family of positive RNA viruses, have a broader host spectrum and cause serious health threats to human and animals. Prior to the emergence of SARS-CoV, CoVs have been known in animals for several decades. Except the economic importance in the veterinary fields, the existence of coronavirus quasispecies and the high rate of mutation and recombination foster the emergence of new CoV strains with altered cell tropisms and host specificity, which raises the specter of potential future outbreaks of zoonotic SARS-CoV-like diseases in humans. An understanding of animal CoV infections in the natural host is critical to provide a One Health perspective and insights on common and distinctive disease mechanisms related to human CoV infection such as SARS-CoV and SARS-CoV-2.

In this special issue of Viruses, we invite the submission of original research papers and review articles spanning the entire spectrum of animal coronaviruses including molecular mechanisms mediating virus virulence, molecular basis of virus replication, virus pathogenesis, host immune response involved in protection against infection, development of different types of vaccines.

Prof. Dr. Pinghuang Liu
Guest Editor

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Viruses is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • animal coronavirus
  • host factors
  • virus replication
  • pathogenesis
  • antivirals and vaccines
  • tropism

Published Papers (9 papers)

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Research

Jump to: Review

13 pages, 5761 KiB  
Article
Cross-Neutralization of SARS-CoV-2-Specific Antibodies in Convalescent and Immunized Human Sera against the Bat and Pangolin Coronaviruses
by Kanjana Srisutthisamphan, Janya Saenboonrueng, Asawin Wanitchang, Ratchanont Viriyakitkosol and Anan Jongkaewwattana
Viruses 2022, 14(8), 1793; https://doi.org/10.3390/v14081793 - 16 Aug 2022
Cited by 2 | Viewed by 1806
Abstract
Coronaviruses isolated from bats and pangolins are closely related to SARS-CoV-2, the causative agent of COVID-19. These so-called sarbecoviruses are thought to pose an acute pandemic threat. As SARS-CoV-2 infection and vaccination have become more widespread, it is not known whether neutralizing antibodies [...] Read more.
Coronaviruses isolated from bats and pangolins are closely related to SARS-CoV-2, the causative agent of COVID-19. These so-called sarbecoviruses are thought to pose an acute pandemic threat. As SARS-CoV-2 infection and vaccination have become more widespread, it is not known whether neutralizing antibodies to SARS-CoV-2 can cross-neutralize coronaviruses transmitted by bats or pangolins. In this study, we analyzed antibody-mediated neutralization with serum samples from COVID-19 patients (n = 31) and those immunized with inactivated SARS-CoV-2 vaccines (n = 20) against lentivirus-based pseudo-viruses carrying the spike derived from ancestral SARS-CoV-2, bat (RaTG13 or RshSTT182), or pangolin coronaviruses (PCoV-GD). While SARS-CoV-2, PCoV-GD, and RshSTT182 spikes could promote cell-cell fusion in VeroE6 cells, the RaTG13 spike did not. RaTG13, on the other hand, was able to induce cell-cell fusion in cells overexpressing ACE2. Dramatic differences in neutralization activity were observed, with the highest level observed for RaTG13, which was even significantly higher than SARS-CoV-2, PCoV-GD, and RshSTT182 pseudo-viruses. Interestingly, pseudo-viruses containing the chimeric protein in which the receptor-binding domain (RBD) of PCoV-GD spike was replaced by that of RaTG13 could be strongly neutralized, whereas those carrying RaTG13 with the RBD of PCoV-GD were significantly less neutralized. Because the high neutralizing activity against RaTG13 appears to correlate with its low affinity for binding to the human ACE2 receptor, our data presented here might shed light on how pre-existing immunity to SARS-CoV-2 might contribute to protection against related sarbecoviruses with potential spillover to the human host. Full article
(This article belongs to the Special Issue Animal Coronavirus Pathogenesis and Immunity)
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20 pages, 4095 KiB  
Article
Antigenicity Alternations of Variant PEDV S Protein Disclosed by Linear B Cell Epitope Mapping
by Ruisong Yu, Shijuan Dong, Bingqing Chen, Yingjie Liu, Fengping Li, Fusheng Si, Chunfang Xie and Zhen Li
Viruses 2022, 14(7), 1371; https://doi.org/10.3390/v14071371 - 23 Jun 2022
Cited by 1 | Viewed by 1756
Abstract
The spike protein (S) plays a crucial role in porcine epidemic diarrhea virus (PEDV) infection and induces neutralizing antibodies. Mutations of the S protein are supposed to provide the main antigenic shift leading to the antigenic escape of PEDVs. It is therefore a [...] Read more.
The spike protein (S) plays a crucial role in porcine epidemic diarrhea virus (PEDV) infection and induces neutralizing antibodies. Mutations of the S protein are supposed to provide the main antigenic shift leading to the antigenic escape of PEDVs. It is therefore a significant question how much accumulation of antigenic shift could lead to the antigenic escape of the variant PEDV. To provide an answer in the study, B cell epitopes (BCEs) on the S protein of the PEDV vaccine strain CV777 (SCV777) and variant strain SD2014 (SSD2014) were mapped using biosynthetic peptides and rabbit anti-PEDV S serum. Seventy-nine and 68 linear BCEs were identified from SCV777 and SSD2014, respectively. While 66.2% of the BCEs of SSD2014 could be recognized by anti-SCV777 serum and 67.1% of SCV777 BCEs could be recognized by anti-SSD2014 serum, more than 40% of the BCEs identified using anti-SCV777 serum on SCV777 could not be recognized by anti-SSD2014 serum and vice versa. The completely shared BCEs took low percentages of 29.4% and 25.3% for SSD2014 and SCV777, respectively. These results indicate a low conservation of antigenicity of the S protein compared to a relatively high amino acid sequence similarity of 92.2% between the two strains. The study provided a BCE shift reference of PEDV antigenic escape and surveillance control. Full article
(This article belongs to the Special Issue Animal Coronavirus Pathogenesis and Immunity)
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19 pages, 4166 KiB  
Article
Serotype I and II Feline Coronavirus Replication and Gene Expression Patterns of Feline Cells—Building a Better Understanding of Serotype I FIPV Biology
by Sarah Cook, Diego Castillo, Sonyia Williams, Christine Haake and Brian Murphy
Viruses 2022, 14(7), 1356; https://doi.org/10.3390/v14071356 - 22 Jun 2022
Cited by 6 | Viewed by 2912
Abstract
Feline infectious peritonitis (FIP) is a disease of domestic cats caused by the genetic variant of the feline coronavirus (FCoV) and feline infectious peritonitis virus (FIPV), currently grouped into two serotypes, I and II. Although serotype I FIPV is more prevalent in cats [...] Read more.
Feline infectious peritonitis (FIP) is a disease of domestic cats caused by the genetic variant of the feline coronavirus (FCoV) and feline infectious peritonitis virus (FIPV), currently grouped into two serotypes, I and II. Although serotype I FIPV is more prevalent in cats with FIP, serotype II has been more extensively studied in vitro due to the relative ease in propagating this viral serotype in culture systems. As a result, more is known about serotype II FIPV than the more biologically prevalent serotype I. The primary cell receptor for serotype II has been determined, while it remains unknown for serotype I. The recent development of a culture-adapted feline cell line that more effectively propagates serotype I FIPV, FCWF-4 CU, derived from FCWF-4 cells available through the ATCC, offers the potential for an improved understanding of serotype I FIPV biology. To learn more about FIPV receptor biology, we determined targeted gene expression patterns in feline cells variably permissive to replication of serotype I or II FIPV. We utilized normal feline tissues to determine the immunohistochemical expression patterns of two known coronavirus receptors, ACE2 and DC-SIGN. Lastly, we compared the global transcriptomes of the two closely related FCWF-4 cell lines and identified viral transcripts with potential importance for the differential replication kinetics of serotype I FIPV. Full article
(This article belongs to the Special Issue Animal Coronavirus Pathogenesis and Immunity)
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27 pages, 6020 KiB  
Article
SARS CoV-2 (Delta Variant) Infection Kinetics and Immunopathogenesis in Domestic Cats
by Miruthula Tamil Selvan, Sachithra Gunasekara, Ping Xiao, Kristen Griffin, Shannon R. Cowan, Sai Narayanan, Akhilesh Ramachandran, Darren E. Hagen, Jerry W. Ritchey, Jennifer M. Rudd and Craig A. Miller
Viruses 2022, 14(6), 1207; https://doi.org/10.3390/v14061207 - 01 Jun 2022
Cited by 5 | Viewed by 4212
Abstract
Continued emergence of SARS-CoV-2 variants highlights the critical need for adaptable and translational animal models for acute COVID-19. Limitations to current animal models for SARS CoV-2 (e.g., transgenic mice, non-human primates, ferrets) include subclinical to mild lower respiratory disease, divergence from clinical COVID-19 [...] Read more.
Continued emergence of SARS-CoV-2 variants highlights the critical need for adaptable and translational animal models for acute COVID-19. Limitations to current animal models for SARS CoV-2 (e.g., transgenic mice, non-human primates, ferrets) include subclinical to mild lower respiratory disease, divergence from clinical COVID-19 disease course, and/or the need for host genetic modifications to permit infection. We therefore established a feline model to study COVID-19 disease progression and utilized this model to evaluate infection kinetics and immunopathology of the rapidly circulating Delta variant (B.1.617.2) of SARS-CoV-2. In this study, specific-pathogen-free domestic cats (n = 24) were inoculated intranasally and/or intratracheally with SARS CoV-2 (B.1.617.2). Infected cats developed severe clinical respiratory disease and pulmonary lesions at 4- and 12-days post-infection (dpi), even at 1/10 the dose of previously studied wild-type SARS-CoV-2. Infectious virus was isolated from nasal secretions of delta-variant infected cats in high amounts at multiple timepoints, and viral antigen was co-localized in ACE2-expressing cells of the lungs (pneumocytes, vascular endothelium, peribronchial glandular epithelium) and strongly associated with severe pulmonary inflammation and vasculitis that were more pronounced than in wild-type SARS-CoV-2 infection. RNA sequencing of infected feline lung tissues identified upregulation of multiple gene pathways associated with cytokine receptor interactions, chemokine signaling, and viral protein–cytokine interactions during acute infection with SARS-CoV-2. Weighted correlation network analysis (WGCNA) of differentially expressed genes identified several distinct clusters of dysregulated hub genes that are significantly correlated with both clinical signs and lesions during acute infection. Collectively, the results of these studies help to delineate the role of domestic cats in disease transmission and response to variant emergence, establish a flexible translational model to develop strategies to prevent the spread of SARS-CoV-2, and identify potential targets for downstream therapeutic development. Full article
(This article belongs to the Special Issue Animal Coronavirus Pathogenesis and Immunity)
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15 pages, 2515 KiB  
Article
Infectious Bronchitis Virus Nsp14 Degrades JAK1 to Inhibit the JAK-STAT Signaling Pathway in HD11 Cells
by Peng Ma, Kui Gu, Hao Li, Yu Zhao, Chao Li, Renqiao Wen, Changyu Zhou, Changwei Lei, Xin Yang and Hongning Wang
Viruses 2022, 14(5), 1045; https://doi.org/10.3390/v14051045 - 14 May 2022
Cited by 6 | Viewed by 2247
Abstract
Coronaviruses (CoVs) are RNA viruses that can infect a wide range of animals, including humans, and cause severe respiratory and gastrointestinal disease. The Gammacoronavirus avian infectious bronchitis virus (IBV) causes acute and contagious diseases in chickens, leading to severe economic losses. Nonstructural protein [...] Read more.
Coronaviruses (CoVs) are RNA viruses that can infect a wide range of animals, including humans, and cause severe respiratory and gastrointestinal disease. The Gammacoronavirus avian infectious bronchitis virus (IBV) causes acute and contagious diseases in chickens, leading to severe economic losses. Nonstructural protein 14 (Nsp14) is a nonstructural protein encoded by the CoV genome. This protein has a regulatory role in viral virulence and replication. However, the function and mechanism of IBV Nsp14 in regulating the host’s innate immune response remain unclear. Here we report that IBV Nsp14 was a JAK-STAT signaling pathway antagonist in chicken macrophage (HD11) cells. In these cells, Nsp14 protein overexpression blocked IBV suppression induced by exogenous chIFN-γ treatment. Meanwhile, Nsp14 remarkably reduced interferon-gamma-activated sequence (GAS) promoter activation and chIFN-γ-induced interferon-stimulated gene expression. Nsp14 impaired the nuclear translocation of chSTAT1. Furthermore, Nsp14 interacted with Janus kinase 1 (JAK1) to degrade JAK1 via the autophagy pathway, thereby preventing the activation of the JAK-STAT signaling pathway and facilitating viral replication. These results indicated a novel mechanism by which IBV inhibits the host antiviral response and provide new insights into the selection of antiviral targets against CoV. Full article
(This article belongs to the Special Issue Animal Coronavirus Pathogenesis and Immunity)
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30 pages, 1101 KiB  
Article
Alpha-1 Acid Glycoprotein Reduction Differentiated Recovery from Remission in a Small Cohort of Cats Treated for Feline Infectious Peritonitis
by Diane D. Addie, Carla Silveira, Charlotte Aston, Pauline Brauckmann, Johanna Covell-Ritchie, Chris Felstead, Mark Fosbery, Caryn Gibbins, Kristina Macaulay, James McMurrough, Ed Pattison and Elise Robertson
Viruses 2022, 14(4), 744; https://doi.org/10.3390/v14040744 - 01 Apr 2022
Cited by 8 | Viewed by 6705
Abstract
Feline infectious peritonitis (FIP) is a systemic immune-mediated inflammatory perivasculitis that occurs in a minority of cats infected with feline coronavirus (FCoV). Various therapies have been employed to treat this condition, which was previously usually fatal, though no parameters for differentiating FIP recovery [...] Read more.
Feline infectious peritonitis (FIP) is a systemic immune-mediated inflammatory perivasculitis that occurs in a minority of cats infected with feline coronavirus (FCoV). Various therapies have been employed to treat this condition, which was previously usually fatal, though no parameters for differentiating FIP recovery from remission have been defined to enable clinicians to decide when it is safe to discontinue treatment. This retrospective observational study shows that a consistent reduction of the acute phase protein alpha-1 acid glycoprotein (AGP) to within normal limits (WNL, i.e., 500 μg/mL or below), as opposed to duration of survival, distinguishes recovery from remission. Forty-two cats were diagnosed with FIP: 75% (12/16) of effusive and 54% (14/26) of non-effusive FIP cases recovered. Presenting with the effusive or non-effusive form did not affect whether or not a cat fully recovered (p = 0.2). AGP consistently reduced to WNL in 26 recovered cats but remained elevated in 16 cats in remission, dipping to normal once in two of the latter. Anaemia was present in 77% (23/30) of the cats and resolved more quickly than AGP in six recovered cats. The presence of anaemia did not affect the cat’s chances of recovery (p = 0.1). Lymphopenia was observed in 43% (16/37) of the cats and reversed in nine recovered cats but did not reverse in seven lymphopenic cats in the remission group. Fewer recovered cats (9/24: 37%) than remission cats (7/13: 54%) were lymphopenic, but the difference was not statistically different (p = 0.5). Hyperglobulinaemia was slower than AGP to return to WNL in the recovered cats. FCoV antibody titre was high in all 42 cats at the outset. It decreased significantly in 7 recovered cats but too slowly to be a useful parameter to determine discontinuation of antiviral treatments. Conclusion: a sustained return to normal levels of AGP was the most rapid and consistent indicator for differentiating recovery from remission following treatment for FIP. This study provides a useful model for differentiating recovery from chronic coronavirus disease using acute phase protein monitoring. Full article
(This article belongs to the Special Issue Animal Coronavirus Pathogenesis and Immunity)
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15 pages, 3427 KiB  
Article
Porcine Deltacoronavirus (PDCoV) Entry into PK-15 Cells by Caveolae-Mediated Endocytosis
by Shiqian Li, Dai Xiao, Yujia Zhao, Luwen Zhang, Rui Chen, Weizhe Liu, Yimin Wen, Yijie Liao, Yiping Wen, Rui Wu, Xinfeng Han, Qin Zhao, Senyan Du, Qigui Yan, Xintian Wen, Sanjie Cao and Xiaobo Huang
Viruses 2022, 14(3), 496; https://doi.org/10.3390/v14030496 - 28 Feb 2022
Cited by 6 | Viewed by 2691
Abstract
(1) Background: Porcine deltacoronavirus (PDCoV) is a newly emerged enteric virus affecting pig breeding industries worldwide, and its pathogenic mechanism remains unclear. (2) Methods: In this study, we preliminarily identified the endocytic pathway of PDCoV in PK-15 cells, using six chemical inhibitors (targeting [...] Read more.
(1) Background: Porcine deltacoronavirus (PDCoV) is a newly emerged enteric virus affecting pig breeding industries worldwide, and its pathogenic mechanism remains unclear. (2) Methods: In this study, we preliminarily identified the endocytic pathway of PDCoV in PK-15 cells, using six chemical inhibitors (targeting clathrin-mediated endocytosis, caveolae-mediated endocytosis, macropinocytosis pathway and endosomal acidification), overexpression of dominant-negative (DN) mutants to treat PK-15 cells and proteins knockdown. (3) Results: The results revealed that PDCoV entry was not affected after treatment with chlorpromazine (CPZ), 5-(N-ethyl-N-isopropyl) amiloride (EIPA)or ammonium chloride (NH4Cl), indicating that the entry of PDCoV into PK-15 cells were clathrin-, micropinocytosis-, PH-independent endocytosis. Conversely, PDCoV infection was sensitive to nystatin, dynasore and methyl-β-cyclodextrin (MβCD) with reduced PDCoV internalization, indicating that entry of PDCoV into PK-15 cells was caveolae-mediated endocytosis that required dynamin and cholesterol; indirect immunofluorescence and shRNA interference further validated these results. (4) Conclusions: In conclusion, PDCoV entry into PK-15 cells depends on caveolae-mediated endocytosis, which requires cholesterol and dynamin. Our finding is the first initial identification of the endocytic pathway of PDCoV in PK-15 cells, providing a theoretical basis for an in-depth understanding of the pathogenic mechanism of PDCoV and the design of new antiviral targets. Full article
(This article belongs to the Special Issue Animal Coronavirus Pathogenesis and Immunity)
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Review

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7 pages, 1141 KiB  
Review
An Updated Review on SARS-CoV-2 Infection in Animals
by Shujuan Cui, Yimeng Liu, Jiachen Zhao, Xiaomin Peng, Guilan Lu, Weixian Shi, Yang Pan, Daitao Zhang, Peng Yang and Quanyi Wang
Viruses 2022, 14(7), 1527; https://doi.org/10.3390/v14071527 - 13 Jul 2022
Cited by 29 | Viewed by 3186
Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has lasted for two years and caused millions of infections and deaths in humans. Although the origin of SARS-CoV-2 infection in humans remains unknown, infection in animals has been frequently reported in varieties of [...] Read more.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has lasted for two years and caused millions of infections and deaths in humans. Although the origin of SARS-CoV-2 infection in humans remains unknown, infection in animals has been frequently reported in varieties of animals all over the world. Both experimental and natural infections of SARS-CoV-2 in different animal species provide useful information on viral host range and pathogenicity. As the pandemic continues to evolve, SARS-CoV-2 infection in animals will be expanding. In this review, we summarized SARS-CoV-2 testing and infection in animals as well as SARS-CoV-2 strains and transmission in animals. Current data showed that at least 18 different animal species tested positive for SARS-CoV-2. These 18 animal species belong to pet, captive, farmed, and wild animals. Fifteen of the eighteen animal species were known to be positive for the Delta variant and ten animal species were infected with two different types of variants. Human-to-animal, animal-to-animal, and animal-to-human transmission events were suggested in different outbreaks involved in animal infection with SARS-CoV-2. Continued testing, immunization, and surveillance are warranted. Full article
(This article belongs to the Special Issue Animal Coronavirus Pathogenesis and Immunity)
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15 pages, 1198 KiB  
Review
Prevention and Control of Porcine Epidemic Diarrhea: The Development of Recombination-Resistant Live Attenuated Vaccines
by Xiaoyu Niu and Qiuhong Wang
Viruses 2022, 14(6), 1317; https://doi.org/10.3390/v14061317 - 16 Jun 2022
Cited by 11 | Viewed by 2757
Abstract
Porcine epidemic diarrhea (PED), causing up to 100% mortality in neonatal pigs, is a highly contagious enteric disease caused by PED virus (PEDV). The highly virulent genogroup 2 (G2) PEDV emerged in 2010 and has caused huge economic losses to the pork industry [...] Read more.
Porcine epidemic diarrhea (PED), causing up to 100% mortality in neonatal pigs, is a highly contagious enteric disease caused by PED virus (PEDV). The highly virulent genogroup 2 (G2) PEDV emerged in 2010 and has caused huge economic losses to the pork industry globally. It was first reported in the US in 2013, caused country-wide outbreaks, and posed tremendous hardship for many pork producers in 2013–2014. Vaccination of pregnant sows/gilts with live attenuated vaccines (LAVs) is the most effective strategy to induce lactogenic immunity in the sows/gilts and provide a passive protection via the colostrum and milk to suckling piglets against PED. However, there are still no safe and effective vaccines available after about one decade of endeavor. One of the biggest concerns is the potential reversion to virulence of an LAV in the field. In this review, we summarize the status and the major obstacles in PEDV LAV development. We also discuss the function of the transcriptional regulatory sequences in PEDV transcription, contributing to recombination, and possible strategies to prevent the reversion of LAVs. This article provides insights into the rational design of a promising LAV without safety issues. Full article
(This article belongs to the Special Issue Animal Coronavirus Pathogenesis and Immunity)
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