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Figure 1: Taxonomy of HCoVs: the updated classification scheme of HCoV and other coronaviruses. The six known HCoVs are in blue. Abbreviations: BtCoV, bat coronavirus; BuCoV, bulbul coronavirus; HCoV,...

Figure 2: Genome structure of human coronaviruses (HCoVs). Schematic diagram showing the genome structure of six known HCoVs (not to scale). The 5′-cap structure (5′-C) and 3′-polyadenylation (AnAOH-3...

Figure 3: Replication cycle of human coronaviruses (HCoVs). Schematic diagram showing the general replication cycle of HCoVs. Infection starts with the attachment of HCoVs to the cognate cellular rece...

Figure 4: Induction and modulation of autophagy by HCoV infection. Schematic diagram showing the signaling pathway of autophagy and the modulatory mechanisms utilized by HCoV. Viruses and viral compon...

Figure 5: Apoptosis induced by HCoV infection and modulatory mechanisms. Schematic diagram showing the signaling pathway of intrinsic and extrinsic apoptosis induction and the modulatory mechanisms ut...

Figure 6: Induction and modulation of unfolded protein response by HCoV infection. Schematic diagram showing the three branches of UPR signaling pathway activated and regulated by HCoV infection. Viru...

Figure 7: Activation and modulation of MAPK signaling pathways by HCoV infection. Schematic diagram showing the activation and modulation of MAPK signaling pathway by HCoV infection. Viruses and viral...

Figure 8: Type I interferon induction and signaling during HCoV infection and modulatory mechanisms. Schematic diagram showing the induction and signaling pathways of type I interferon during HCoV inf...

Figure 1: Introduction to coronaviruses and their spike proteins. (a) Classification of coronaviruses. Representative coronaviruses in each genus are human coronavirus NL63 (HCoV-NL63), porcine transm...

Figure 2: Cryo–electron microscopy structures of prefusion trimeric coronavirus spikes. (a) Trimeric mouse hepatitis coronavirus (MHV) spike (PDB ID: 3JCL) (16). Three monomers are shown (magenta, cya...

Figure 3: Crystal structures of betacoronavirus S1 C-terminal domains (S1-CTDs). (a) Structure of severe acute respiratory syndrome coronavirus (SARS-CoV) S1-CTD complexed with human ACE2 (PDB ID: 2AJ...

Figure 4: Crystal structures of alphacoronavirus S1 C-terminal domains (S1-CTDs). (a) Structure of human coronavirus NL63 (HCoV-NL63) S1-CTD complexed with human ACE2 (PDB ID: 4KBH) (83). (b) Structur...

Figure 5: Crystal structures of betacoronavirus S1 N-terminal domains (S1-NTDs). (a) Structure of mouse hepatitis coronavirus (MHV) S1-NTD complexed with murine CEACAM1 (PDB ID: 3R4D) (88). The core s...

Figure 6: Structural mechanism for membrane fusion by coronavirus spikes. (a) Structural mechanism for membrane fusion by class I viral membrane fusion proteins. Schematics of these proteins in both p...

Figure 7: Triggers for coronavirus spikes to fuse membranes. Scissors indicate potential spike-processing host proteases. Shown are virus particles (green spheres), virus surface spikes (blue protrusi...

Figure 8: Evolution of coronavirus spikes. (a) Structural comparison between human galectins and alphacoronavirus HCoV-NL63 S1-CTD. Both the crystal structures and structural topologies of the two pro...

Figure 1: Phylogenetic tree of 36 whole-genome coronavirus sequences. Sequences were aligned using ClustalW. The phylogenetic tree was generated using maximum likelihood with the PhyML package (149) a...

Figure 2: (a) Human angiotensin-converting enzyme 2 (ACE2) (light blue) bound to the severe acute respiratory syndrome coronavirus (SARS-CoV) receptor-binding domain (RBD) (red) (PDB 2AJF), with homol...

Figure 3: (a) Human dipeptidyl peptidase 4 (DPP4) (green) bound to the Middle East respiratory syndrome coronavirus (MERS-CoV) receptor-binding domain (RBD) (purple) (PDB 4L72). (b) DPP4 blade 4 has t...

Figure 4: (a) Human dipeptidyl peptidase 4 (DPP4) (green) bound to the Middle East respiratory syndrome coronavirus (MERS-CoV) receptor-binding domain (RBD) (pink) (PDB 4L72) overlaid by human DPP4 bo...

Figure 5: Phylogenetic tree of dipeptidyl peptidase 4 (DPP4) genes, adapted with permission from Cui et al. (49). Blue indicates permissive hosts (dark blue, experimentally determined in vivo or in vi...

Figure 6: (a–c) PyMOL visualization of crystal structures of human dipeptidyl peptidase 4 (DPP4) (green) (PDB 4L72, chain A) aligned structurally to (a) DPP8 (blue), (b) DPP9 (orange), and (c) fibrobl...

Figure 1: Case distribution of Middle East respiratory syndrome coronavirus (MERS-CoV) in the Kingdom of Saudi Arabia (KSA), 2013–2016. The total (a) and percentage (b) of primary, secondary, or unkno...

Figure 1: Scheme of N protein from different CoVs. The organization of N protein from four representative CoVs of genera α (TGEV), β (MHV and SARS-CoV), and γ (IBV) is indicated. Conserved predicted s...

Figure 2: Three-step working model of CoV transcription. (I) 5′-3′ complex formation step. Proteins binding the 5′ and 3′ end TGEV sequences are represented by ellipsoids. Leader sequence is indicated...

Figure 3: RNA chaperone involvement in template switching during CoV transcription. Left panel: Scheme of RNA chaperone activity. Right panel: Template switching step and elements involved. RNA chaper...

Figure 1: Coronavirus genome organization and replication strategy. (a) Open reading frame (ORF) 1ab encompasses roughly two-thirds of the genome and encodes the replicase nonstructural proteins (nsp1...

Figure 2: Replication fidelity in RNA viruses and DNA-based organisms. Shown is the estimated range of mutation rates (dashed arrows) for RNA viruses, coronaviruses, and cellular DNA replication. The ...

Figure 3: Fidelity variants of RNA viruses. Published RNA virus fidelity variants (excluding retroviruses) are shown. For each variant, the fold change in replication fidelity was calculated using pre...

Figure 4: Size of positive-sense single-stranded RNA [(+)ssRNA] virus genomes and expansion of the coronavirus (CoV) genome. (a) Median genome size for (+)ssRNA viruses, excluding the nidoviruses, in ...

Figure 5: Model of the putative coronavirus multisubunit polymerase. The viral genome is shown in light gray and negative-sense template RNA in dark gray. The viral helicase and NTPase (nsp13 Hel/NTPa...

Figure 1: Pandemic curve of probable cases of severe acute respiratory syndrome. This graph does not include 2,527 probable cases of SARS (2,521 from Beijing, China), for whom no dates of onset are ...

Figure 1: Glycans as viral receptors. Host- and cell-specific variants of (a) sialic acids, (b) neutral oligosaccharides such as histo–blood group antigens (HBGAs), and (c) glycosaminoglycans (GAGs) a...

Figure 2: A highly plastic sialic acid–binding site on polyomavirus VP1. Panels a–f show views into the ligand-binding sites of six polyomaviruses for which structural data are currently available. Th...

Figure 3: Engagement of differently O-acetylated 5-N-acetylneuraminic acid (Neu5Ac) by the hemagglutinin esterase (HE) proteins of bovine coronavirus (BCoV) and mouse hepatitis virus strain S (MHV-S)....

Figure 4: Adaptation of a new glycan-binding site on reovirus σ1. Crystal structures of reovirus (a) type 3 Dearing (T3D) σ1 in complex with the GM3 glycan (PDB ID 3S6X; 76) and (b) type 1 Lang (T1L) ...

Figure 5: Engagement of different classes of glycans in a conserved location on the rotavirus spike protein VP8*. (a) A view into the ligand-binding site of porcine rotavirus CRW-8 VP8* bound to the G...

Figure 1: The immunity-related IFITM genes (IFITM1, IFITM2, and IFITM3), together with the osteoblast-restricted IFITM5, form a gene cluster in humans that is conserved in mice and chickens (25, 26). ...

Figure 2: The topological domains of the IFITM proteins are shown above an alignment of immunity-related IFITM proteins of humans (h), mice (m), chickens (c), and fish (rainbow trout) (f). Domains con...

Figure 3: Three models of IFITM protein transmembrane topology. (a) The predicted type III transmembrane topology with ER-luminal N and C termini. In support of this model, several flow cytometry stud...

Figure 4: IFITM protein localization depends on the particular IFITM protein, cell type, and expression level. (a) A549 cells were transduced with an N-terminally Myc-tagged IFITM3 construct. Myc-IFIT...

Figure 1: Coronavirus genome structure and gene expression. (a) Coronavirus genome structure. The upper scheme represents the TGEV genome. Labels indicate gene names; L corresponds to the leader seque...

Figure 2: Model for the formation of genome high-order structures regulating N gene transcription. The upper linear scheme represents the coronavirus genome. The red line indicates the leader sequence...

Figure 3: Three-step model of coronavirus transcription. () Complex formation. Proteins binding transcription-regulating sequences are represented by ellipsoids, the leader sequence is indicated with ...

Figure 4: Coronavirus cis-acting RNA elements. The higher-order RNA structures indicated in the diagram are mainly based on studies done in betacoronaviruses. The core sequence within the leader trans...

Figure 5: Coronavirus replication-transcription complex. (a) After binding of the nsp8, nsp7, and nsp9 complex to the genomic RNA 3′ end, the nsp8 primase activity initiates RNA synthesis de novo. Thi...

Figure 1: Relative size and components of an antibody molecule. (a) Full-length human immunoglobulin G subclass 1 (IgG1) (PDB ID: 1IGT) is a dimer of heterodimers composed of two heavy chains (dark or...

Figure 2: Epitopes present on two major conformations of the respiratory syncytial virus (RSV) F glycoprotein. The prefusion conformation of RSV F (pre-F) is shown with two protomers in gray and white...

Figure 3: Representative trimeric fusion proteins from selected virus families (Coronaviridae, Orthomyxoviridae, Filoviridae, Pneumoviridae, Retroviridae, Arenaviridae, and Paramyxoviridae) are shown ...

Figure 1: The geographic spread and zoonotic transmission of New World hantaviruses, Nipah virus, and Middle East respiratory syndrome coronavirus (MERS-CoV). Endemic regions where human cases have be...

Figure 2: Disease progression in patients infected with New World hantaviruses, Nipah virus, or MERS-CoV. The different stages of disease are indicated, along with incubation time and minimum time fro...

Figure 3: Gross pathological and radiographic changes in the lungs of nonhuman primates experimentally infected with a hantavirus, Nipah virus, or Middle East respiratory syndrome coronavirus (MERS-Co...

Figure 4: Histopathological changes in the lungs of nonhuman primates experimentally infected with a hantavirus, Nipah virus, or Middle East respiratory syndrome coronavirus (MERS-CoV). Lungs were col...

Figure 1: Intestinal epithelium and preferred virus replication sites: Enteric viruses have predilection for different parts of intestinal epithelium and may cause diarrhea by different mechanisms. On...

Figure 2: Gut–mammary gland–sIgA axis in sows: Infection of naïve pregnant sows (or other monogastrics) by enteric pathogens (i.e., coronaviruses, rotaviruses) or immunization with live oral vaccines ...

Figure 3: Preweaning diarrhea scenario in piglets. Lactogenic immunity received from vaccinated (oral attenuated or boosting of orally primed sows with inactivated vaccine) or naturally infected sows ...

Figure 1: Role of ACE2 in acute lung injury. ACE converts angiotensin I to angiotensin II, which binds either to angiotensin II receptor 1a (AT1aR), leading to tissue damage and lung edema, or to angi...

Figure 2: A model of SARS pathogenesis. Blue arrows are used where data are available to support the model, and gray arrows are used for pathways/steps that are proposed. SARS-CoV infects pneumocytes ...

Figure 1: Phylogenetic relationships among 37 Felidae species and 7 outgroup taxa based on a maximum likelihood tree derived from 22,789 base pairs (bp) (37). Terminal species are labeled with three-l...

Figure 2: Range map and geographic partitions of six validated puma subspecies as defined by analysis of mitochondrial DNA (mtDNA) and microsatellites (16). Letters indicate captive location and mtDNA...

Figure 3: Range of modern leopard subspecies revealed by mitochrondrial DNA (mtDNA) and microsatellite phylogenetic analyses. The subspecies indicated by separate colors are Panthera pardus pardus (PA...

Figure 4: Phylogenetic relationships based on maximum parsimony (MP) among the tiger mtDNA haplotypes from 4078 bp mitochondrial DNA (mtDNA) sequence (45). Branches of the same color represent haploty...

Figure 5: Phylogenetic tree of human and domestic animal coronavirus sequences (pol lb gene), including the Aju-CoV from cheetahs involved in the 1982 feline infectious peritonitis (FIP) outbreak in O...

Figure 1: Viral genomes and expression. RNA genomes and encoded proteins of (a) Brome mosaic virus, Flock House virus, dengue virus, poliovirus, and (b) severe acute respiratory syndrome (SARS) virus....

Figure 2: Brome mosaic virus (BMV)-induced perinuclear endoplasmic reticulum (ER)-associated membrane spherules. (a, b) Low and high magnifications of a yeast cell expressing BMV1a. (c) Nuclear membra...

Figure 3: Flock House virus (FHV)-induced spherular invaginations of the outer mitochondrial membrane. Three-dimensional electron microscope tomography of FHV-induced spherules in a mitochondrion of a...

Figure 4: Continuous ER-derived membranous networks in dengue virus (DENV)-infected cells. (a) DENV-induced convoluted membranes, vesicles, and tubular structures form a continuous network of ER-deriv...

Figure 5: Membranous interconnected network of severe acute respiratory syndrome (SARS) virus-induced double-membrane vesicles. Electron microscope tomography-based, three-dimensional surface-rendered...

Figure 6: Poliovirus (PV)-induced vesicle clusters. (a) Electron microscope (EM) image of vesicular membrane rearrangements in PV-infected cells. (b) EM image of extracted vesicle clusters showing a t...

Figure 1: Illustration of viroporin motifs and conductance states. A viroporin (brown) is shown inserted into a lipid bilayer. Positively charged residues such as lysine or arginine anchor the viropor...

Figure 2: Viroporin-mediated disruption in calcium signaling by NSP4 and 2B. Changes to host cell Ca2+ homeostasis induced by (a) rotavirus NSP4 and (b) picornavirus 2B, with potential changes in Ca2+...