Coronaviruses: An Overview of Their Replication and Pathogenesis

Fehr, Anthony R.; Perlman, Stanley

doi:10.1007/978-1-4939-2438-7_1

Cited by 3,368 publications

(4,017 citation statements)

References 156 publications

Supporting

Mentioning

3,789

Contrasting

Unclassified

217

Order By: Relevance

“…Envelope appears specific to betacoronavirus (fig. 1), but it is a short protein that has been found to diverge rapidly and is likely present outside betacoronavirus (Fehr and Perlman 2015). Because different protein families yield slightly different phylogenies, for the remaining evolutionary analyses, every protein family was analyzed in the context of its own phylogeny.…”

Section: Resultsmentioning

confidence: 99%

Avoiding Regions Symptomatic of Conformational and Functional Flexibility to Identify Antiviral Targets in Current and Future Coronaviruses

Rahaman

Siltberg-Liberles

2016

Genome Biology and Evolution

View full text Add to dashboard Cite

Within the last 15 years, two related coronaviruses (Severe Acute Respiratory Syndrome [SARS]-CoV and Middle East Respiratory Syndrome [MERS]-CoV) expanded their host range to include humans, with increased virulence in their new host. Coronaviruses were recently found to have little intrinsic disorder compared with many other virus families. Because intrinsically disordered regions have been proposed to be important for rewiring interactions between virus and host, we investigated the conservation of intrinsic disorder and secondary structure in coronaviruses in an evolutionary context. We found that regions of intrinsic disorder are rarely conserved among different coronavirus protein families, with the primary exception of the nucleocapsid. Also, secondary structure predictions are only conserved across 50–80% of sites for most protein families, with the implication that 20–50% of sites do not have conserved secondary structure prediction. Furthermore, nonconserved structure sites are significantly less constrained in sequence divergence than either sites conserved in the secondary structure or sites conserved in loop. Avoiding regions symptomatic of conformational flexibility such as disordered sites and sites with nonconserved secondary structure to identify potential broad-specificity antiviral targets, only one sequence motif (five residues or longer) remains from the >10,000 starting sites across all coronaviruses in this study. The identified sequence motif is found within the nonstructural protein (NSP) 12 and constitutes an antiviral target potentially effective against the present day and future coronaviruses. On shorter evolutionary timescales, the SARS and MERS clades have more sequence motifs fulfilling the criteria applied. Interestingly, many motifs map to NSP12 making this a prime target for coronavirus antivirals.

show abstract

Section: Resultsmentioning

confidence: 99%

Avoiding Regions Symptomatic of Conformational and Functional Flexibility to Identify Antiviral Targets in Current and Future Coronaviruses

Rahaman

Siltberg-Liberles

2016

Genome Biology and Evolution

View full text Add to dashboard Cite

show abstract

“…MERS-CoV is a large single-strand positive-sense RNA virus (figure 1). [14][15][16][17][18] The 30-31 kb coronavirus genome encodes a large number of proteins, which might confer versa tility in adapting to new environments and enhance cross-species transmission. MERS-CoV has four struc tural proteins: spike (S) protein, envelope (E)protein, membrane (M) protein, and nucleocapsid (N) protein.…”

Section: Virologymentioning

confidence: 99%

“…77,78 Imaging A range of abnormal but non-specific chest x-ray findings are seen in patients with MERS. 91,92 These abnormal ities include unilateral or bilateral bronchovascular shadowing, interstitial infiltrates, reticular opacities, reticulonodular shadowing, nodules, pleural effusions, and patchy to confluent consolidation (appendix pp [18][19]. Lower lobes tend to be affected more than upper lobes early in the course of MERS and rapid opacification of lungs and progression to acute respiratory distress syndrome can occur.…”

Section: Laboratory Testingmentioning

confidence: 99%

Middle East respiratory syndrome

et al. 2020

Self Cite

View full text Add to dashboard Cite

The Middle East respiratory syndrome coronavirus (MERS-CoV) is a lethal zoonotic pathogen that was first identified in humans in Saudi Arabia and Jordan in 2012. Intermittent sporadic cases, community clusters, and nosocomial outbreaks of MERS-CoV continue to occur. Between April 2012 and December 2019, 2499 laboratory-confirmed cases of MERS-CoV infection, including 858 deaths (34·3% mortality) were reported from 27 countries to WHO, the majority of which were reported by Saudi Arabia (2106 cases, 780 deaths). Large outbreaks of human-to-human transmission have occurred, the largest in Riyadh and Jeddah in 2014 and in South Korea in 2015. MERS-CoV remains a high-threat pathogen identified by WHO as a priority pathogen because it causes severe disease that has a high mortality rate, epidemic potential, and no medical countermeasures. This Seminar provides an update on the current knowledge and perspectives on MERS epidemiology, virology, mode of transmission, pathogenesis, diagnosis, clinical features, management, infection control, development of new therapeutics and vaccines, and highlights unanswered questions and priorities for research, improved management, and prevention.

show abstract

“…They are broadly distributed among mammalian and avian species, and they cause acute and persistent infections. In most cases, coronaviruses are generally associated with significant respiratory and/or intestinal tract diseases (1,2). Porcine epidemic diarrhea virus (PEDV) has been identified as the etiologic agent of porcine epidemic diarrhea (PED), and it causes diarrhea, vomiting, and dehydration in infected swine (3,4).…”

mentioning

confidence: 99%

Tight Junction Protein Occludin Is a Porcine Epidemic Diarrhea Virus Entry Factor

Luo

Guo

Zhang

et al. 2017

J Virol

View full text Add to dashboard Cite

Porcine epidemic diarrhea virus (PEDV), the causative agent of porcine epidemic diarrhea, has caused huge economic losses in pig-producing countries. Although PEDV was long believed to replicate in the intestinal epithelium by using aminopeptidase N as a receptor, the mechanisms of PEDV infection are not fully characterized. In this study, we found that PEDV infection of epithelial cells results in disruption of the tight junctional distribution of occludin to its intracellular location. Overexpression of occludin in target cells makes them more susceptible to PEDV infection, whereas ablation of occludin expression by use of small interfering RNA (siRNA) in target cells significantly reduces their susceptibility to virus infection. However, the results observed with occludin siRNA indicate that occludin is not required for virus attachment. We conclude that occludin plays an essential role in PEDV infection at the postbinding stages. Furthermore, we observed that macropinocytosis inhibitors blocked occludin internalization and virus entry, indicating that virus entry and occludin internalization are closely coupled. However, the macropinocytosis inhibitors could not impede virus replication once the virus had entered host cells. This suggests that occludin internalization by macropinocytosis or a macropinocytosis-like process is involved in the virus entry events. Immunofluorescence confocal microscopy showed that PEDV was trapped at cellular junctional regions upon macropinocytosis inhibitor treatment, indicating that occludin may serve as a scaffold in the vicinity of virus entry. Collectively, these data show that occludin plays an essential role in PEDV infection during late entry events. Our observation may provide novel insights into PEDV infection and related pathogenesis.IMPORTANCE Tight junctions are highly specialized membrane domains whose main function is to attach adjacent cells to each other, thereby forming intercellular seals. Here we investigate, for the first time, the role of the tight junction protein occludin in PEDV infection. We observed that PEDV infection induced the internalization of occludin. By using genetic modification methods, we demonstrate that occludin plays an essential role in PEDV infection. Moreover, PEDV entry and occludin internalization seem to be closely coupled. Our findings reveal a new mechanism of PEDV infection.KEYWORDS PEDV, occludin, tight junction C oronaviruses are a group of positive-strand RNA viruses belonging to the family Coronaviridae in the order Nidovirales. They are broadly distributed among mammalian and avian species, and they cause acute and persistent infections. In most cases, coronaviruses are generally associated with significant respiratory and/or intestinal tract diseases (1, 2). Porcine epidemic diarrhea virus (PEDV) has been identified as the etiologic agent of porcine epidemic diarrhea (PED), and it causes diarrhea, vomiting, and dehydration in infected swine (3, 4). Outbreaks of PED have occurred frequently in

show abstract

Coronaviruses: An Overview of Their Replication and Pathogenesis

Cited by 3,368 publications

References 156 publications

Avoiding Regions Symptomatic of Conformational and Functional Flexibility to Identify Antiviral Targets in Current and Future Coronaviruses

Avoiding Regions Symptomatic of Conformational and Functional Flexibility to Identify Antiviral Targets in Current and Future Coronaviruses

Middle East respiratory syndrome

Tight Junction Protein Occludin Is a Porcine Epidemic Diarrhea Virus Entry Factor

Contact Info

Product

Resources

About