SARS coronavirus pathogenesis: host innate immune responses and viral antagonism of interferon

Totura, Allison L.; Baric, Ralph S.

doi:10.1016/j.coviro.2012.04.004

Cited by 386 publications

(464 citation statements)

References 98 publications

(105 reference statements)

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“…Furthermore, it has been reported that proinflammatory cytokine mRNAs induced by LPS are more stabilized than in the absence of LPS (Dai et al, 2003;Kishore et al, 1999). Hypersensitivity of PRRs in response to their cognate ligands and enhanced expression of proinflammatory cytokines are contributing factors to severe clinical disease and a prolonged period of recovery (Cheng et al, 2012;Totura and Baric, 2012;Villinger et al, 1999;Wahl-Jensen et al, 2011). Thus, in cases of BRDC that involve BVDV-bacterial co-infections, enhanced pro-inflammatory cytokine secretion in response to bacterial LPS could contribute to more severe clinical disease.…”

Section: Discussionmentioning

confidence: 94%

Bovine viral diarrhea virus type 2 in vivo infection modulates TLR4 responsiveness in differentiated myeloid cells which is associated with decreased MyD88 expression

Schaut¹,

McGill

Neill

et al. 2015

Virus Research

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Symptoms of bovine viral diarrhea virus (BVDV) infection range from subclinical to severe, depending on strain virulence. Several in vitro studies showed BVDV infection impaired leukocyte function. Fewer studies have examined the effects of in vivo BVDV infection on monocyte/macrophage function, especially with strains of differing virulence. We characterized cytokine production by bovine myeloid cells isolated early or late in high (HV) or low virulence (LV) BVDV2 infection. Given BVDV infection may enhance susceptibility to secondary bacterial infection, LPS responses were examined as well. Monocytes from HV and LV infected calves produced higher levels of cytokines compared to cells from controls. In contrast, monocyte-derived macrophage cytokine levels were generally reduced. Modulated cytokine expression in HV BVDV2 macrophages was associated with decreased MyD88 expression, likely due to its interaction with viral NS5A. These data and those of others, suggest that certain Flaviviridae may have evolved strategies for subverting receptor signaling pathways involving MyD88.

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Section: Discussionmentioning

confidence: 94%

Bovine viral diarrhea virus type 2 in vivo infection modulates TLR4 responsiveness in differentiated myeloid cells which is associated with decreased MyD88 expression

Schaut¹,

McGill

Neill

et al. 2015

Virus Research

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“…Downstream of ORF1, the genome also encodes for four structural proteins, the S (spike), E (envelope), M (matrix), and N (nucleoprotein) protein. These genes are interspersed with several additional luxury ORFs, which differ significantly among coronavirus in number, nucleotide sequence, gene order, and function; for SARS-CoV, most of these additional ORFs are indispensable for viral replication but many have been shown to antagonize the innate immune response and influence disease severity (Figure 1) [12]. …”

Section: Coronavirusesmentioning

confidence: 99%

Epigenetic Landscape during Coronavirus Infection

2017

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Coronaviruses (CoV) comprise a large group of emerging human and animal pathogens, including the highly pathogenic severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) strains. The molecular mechanisms regulating emerging coronavirus pathogenesis are complex and include virus–host interactions associated with entry, replication, egress and innate immune control. Epigenetics research investigates the genetic and non-genetic factors that regulate phenotypic variation, usually caused by external and environmental factors that alter host expression patterns and performance without any change in the underlying genotype. Epigenetic modifications, such as histone modifications, DNA methylation, chromatin remodeling, and non-coding RNAs, function as important regulators that remodel host chromatin, altering host expression patterns and networks in a highly flexible manner. For most of the past two and a half decades, research has focused on the molecular mechanisms by which RNA viruses antagonize the signaling and sensing components that regulate induction of the host innate immune and antiviral defense programs upon infection. More recently, a growing body of evidence supports the hypothesis that viruses, even lytic RNA viruses that replicate in the cytoplasm, have developed intricate, highly evolved, and well-coordinated processes that are designed to regulate the host epigenome, and control host innate immune antiviral defense processes, thereby promoting robust virus replication and pathogenesis. In this article, we discuss the strategies that are used to evaluate the mechanisms by which viruses regulate the host epigenome, especially focusing on highly pathogenic respiratory RNA virus infections as a model. By combining measures of epigenome reorganization with RNA and proteomic datasets, we articulate a spatial-temporal data integration approach to identify regulatory genomic clusters and regions that play a crucial role in the host’s innate immune response, thereby defining a new viral antagonism mechanism following emerging coronavirus infection.

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“…Despite their large genome size, infectious particles of many coronaviruses can be recovered successfully in vitro using various technological platforms (Almazán et al, 2014;Totura & Baric, 2012). One of the most effective strategies is either by direct introduction of a full-length cDNA infectious clone into permissible cells or by in vitro transcription of the clone followed by transfection of the full-length RNA.…”

Section: Introductionmentioning

confidence: 99%

Genetic manipulation of porcine epidemic diarrhoea virus recovered from a full-length infectious cDNA clone

Jengarn

Wongthida

Wanasen

et al. 2015

Journal of General Virology

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Porcine epidemic diarrhoea virus (PEDV) causes acute diarrhoea and dehydration in swine of all ages, with significant mortality in neonatal pigs. The recent rise of PEDV outbreaks in Asia and North America warrants an urgent search for effective vaccines. However, PEDV vaccine research has been hampered by difficulties in isolating and propagating the virus in mammalian cells, thereby complicating the recovery of infectious PEDV using a full-length infectious clone. Here, we engineered VeroE6 cells to stably express porcine aminopeptidase N (pAPN) and used them as a platform to obtain a high-growth variant of PEDV, termed PEDV AVCT12 . Subsequently, the full-length cDNA clone was constructed by assembling contiguous cDNA fragments encompassing the complete genome of PEDV AVCT12 in a bacterial artificial chromosome. Infectious PEDV could be recovered, and the rescued virus displayed phenotypic properties identical to the parental virus. Interestingly, we found that PEDV AVCT12 contained a C-terminal deletion of the spike gene, resulting in disruption of the ORF3 start codon. When a functional ORF3 gene was restored, the recombinant virus could not be rescued, suggesting that ORF3 could suppress PEDV replication in vitro. In addition, a high-growth and genetically stable recombinant PEDV expressing a foreign protein could be rescued by replacing the ORF3 gene with the mCherry gene. Together, the results of this study provide a means to generate genetically defined PEDV as a promising vaccine candidate.

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SARS coronavirus pathogenesis: host innate immune responses and viral antagonism of interferon

Cited by 386 publications

References 98 publications

Bovine viral diarrhea virus type 2 in vivo infection modulates TLR4 responsiveness in differentiated myeloid cells which is associated with decreased MyD88 expression

Bovine viral diarrhea virus type 2 in vivo infection modulates TLR4 responsiveness in differentiated myeloid cells which is associated with decreased MyD88 expression

Epigenetic Landscape during Coronavirus Infection

Genetic manipulation of porcine epidemic diarrhoea virus recovered from a full-length infectious cDNA clone

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