Mutations in VP1 and 3A proteins improve binding and replication of rhinovirus C15 in HeLa-E8 cells

Bochkov, Yury A.; Watters, Kelly; Basnet, Sarmila; Sijapati, Shakher; Hill, Marchel; Palmenberg, Ann C.; Gern, James E.

doi:10.1016/j.virol.2016.09.025

Cited by 33 publications

(32 citation statements)

References 55 publications

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“…The initially strong heparin-binding variant acquired an additional mutataion, which confers weak heparin-binding phenotype and high virulence. Furthermore, attenuation of viruses via cell culture adaptation mediated by glycosaminoglycans (including HS) has been reported for many Flaviviridae (e.g., Japanese encephalitis virus, Murray Valley encephalitis virus, West Nile virus, and Dengue virus) [87][88][89][90], Togaviridae (Sindbis virus, Venezuelan equine encephalitis virus, Tickborne encephalitis virus, and Chikungunya virus) [91][92][93][94], and Picornaviridae (human Rhinovirus (HRV) C15, HRV89, and foot and mouth disease virus) [95][96][97]. In addition to this trapping effect, Fujii et al [85] reported that HS-binding strains are more easily neutralized by antibodies than HSnonbinding strains.…”

Section: Hsmentioning

confidence: 99%

Cellular receptors for enterovirus A71

Kobayashi

Koike

2020

J Biomed Sci

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Enterovirus 71 (EV-A71) is one of the major causative agents of hand, foot, and mouth disease. EV-A71 infection is sometimes associated with severe neurological diseases such as acute encephalitis, acute flaccid paralysis, and cardiopulmonary failure. Therefore, EV-A71 is a serious public health concern. Scavenger receptor class B, member 2 (SCARB2) is a type III transmembrane protein that belongs to the CD36 family and is a major receptor for EV-A71. SCARB2 supports attachment and internalization of the virus and initiates conformational changes that lead to uncoating of viral RNA in the cytoplasm. The three-dimensional structure of the virus-receptor complex was elucidated by cryo-electron microscopy. Two α-helices in the head domain of SCARB2 bind to the G-H loop of VP1 and the E-F loop of VP2 capsid proteins of EV-A71. Uncoating takes place in a SCARB2-and low pH-dependent manner. In addition to SCARB2, other molecules support cell surface binding of EV-A71. Heparan sulfate proteoglycans, P-selectin glycoprotein ligand-1, sialylated glycan, annexin II, vimentin, fibronectin, and prohibitin enhance viral infection by retaining the virus on the cell surface. These molecules are known as "attachment receptors" because they cannot initiate uncoating. In vivo, SCARB2 expression was observed in EV-A71 antigenpositive neurons and epithelial cells in the crypts of the palatine tonsils in patients that died of EV-A71 infection. Adult mice are not susceptible to infection by EV-A71, but transgenic mice that express human SCARB2 become susceptible to EV-A71 infection and develop neurological diseases similar to those observed in humans. Attachment receptors may also be involved in EV-A71 infection in vivo. Although heparan sulfate proteoglycans are expressed by many cultured cell lines and enhance infection by a subset of EV-A71 strains, they are not expressed by cells that express SCARB2 at high levels in vivo. Thus, heparan sulfate-positive cells merely adsorb the virus and do not contribute to replication or dissemination of the virus in vivo. In addition to these attachment receptors, cyclophilin A and human tryptophanyl aminoacyl-tRNA synthetase act as an uncoating regulator and an entry mediator that can confer susceptibility to non-susceptibile cells in the absence of SCARB2, respectively. The roles of attachment receptors and other molecules in EV-A71 pathogenesis remain to be elucidated.

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Section: Hsmentioning

confidence: 99%

Cellular receptors for enterovirus A71

Kobayashi

Koike

2020

J Biomed Sci

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“…Capitalizing on this concept, the RV-C receptor hunt switched focus to the Tyr529 variant and was almost instantly rewarded with fully infectious virus amplification systems. The direct and immediate experimental outcomes included tissue culture-adapted virus strains for enhanced growth (12) and satisfactory virus isolation for a high-resolution cryo-electron microscopy (cryoEM) determination of the RV-C15a capsid structure (13). Since that point, RV-C and CDHR3 investigations have been necessarily coevolving.…”

Section: Rv-cmentioning

confidence: 99%

Rhinovirus C, Asthma, and Cell Surface Expression of Virus Receptor CDHR3

Palmenberg

2017

J Virol

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Human rhinoviruses (RVs) of the A, B, and C species are defined agents of the common cold. But more than that, RV-A and RV-C are the dominant causes of hospitalization category infections in young children, especially those with asthma. The use of cadherin-related family member 3 (CDHR3) by RV-C as its cellular receptor creates a direct phenotypic link between human genetics (G versus A alleles cause Cys529 versus Tyr529 protein variants) and the efficiency with which RV-C can infect cells. With a lower cell surface display density, the humanspecific Cys529 variant apparently confers partial protection from the severest virusinduced asthma episodes. Selective pressure favoring the Cys529 codon may have coemerged with the evolution of RV-C and helped shape modern human genomes against the virus-susceptible, albeit ancestral Tyr529.KEYWORDS rhinovirus C, asthma, cadherin structure, common cold, paleogenetics " A lmost everyone has suffered at one time or another, from the sneezing, sniffling, watery-eyed misery of a good old-fashioned common cold. The culpable agent in many cases is a rhinovirus, one of the small, positive-sense RNA-containing picornaviruses, whose very name evokes images of a runny nose." A little over 30 years ago, I started a minireview (1) with that exact statement in a technical article discussing the structure considerations behind experimental failure of peptide-based vaccine directions (quite in vogue at the time) to "cure" the common cold. In the ensuing decades, disappointment, echoing truth, was presaged by the final lines of that review. "Sadly this means that until someone has a better idea, the best advice when you have the sniffles is to stay in bed, drink plenty of liquids and call your doctor in the morning. It will be some time before we can cure the common cold." RV-A AND RV-BIn 1985, the atomic structure of the first rhinovirus (RV), B14, was published (2), and there was great hope in the clinical world that the new data would lead to effective antivirals and vaccines, ridding the United States (alone) of ϳ62 million cases each year of RV-caused colds, which are by far the leading cause of lost work days (adults) and school time (children). The Protein Data Bank (PDB) now has records of Ͼ70 iterations of RV structures (35 for B14 alone) documenting a myriad of receptor and immunogenic complexes, as well as putative antiviral drug interactions. With these data, combined with deep sequencing efforts and phylogenetic considerations, spectacular advances (reviewed in reference 3) have indeed been made in our understanding of the physical and genetic characteristics of these viruses. The canonical isolates in the rhinovirus A (RV-A) and RV-B species cluster as distinct clades in the Enterovirus genus (Picornaviridae), with members sharing Ͼ70% amino acid identity over the nonstructural regions of their polyproteins (ϳ2,150 amino acids [aa]). Within species, further subdivision into genotypes (Ͼ85% nucleotide identity in key capsid regions) is reasonably synonymous with expe...

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“…In addition, some respiratory viruses, such as RVs from species C, grow poorly in standard cell lines. 11 In this respect much effort has been dedicated to develop more representative models, such as airway epithelia reconstituted from primary cells isolated from nasal or bronchial surgeries. These air-liquid interface Abbreviations used dpi: Days after infection EV: Enterovirus HCoV: Human coronavirus HTS: High-throughput RNA sequencing IP-10: Interferon-inducible protein 10 LDH: Lactate dehydrogenase MCC: Mucociliary clearance qPCR: Real-time quantitative PCR RSV: Respiratory syncytial virus RV: Rhinovirus TEER: Transepithelial electrical resistance tissue-culture systems have been validated for the study of respiratory viruses, such as RSV, 12 influenza, 13 human coronaviruses (HCoVs), and RVs.…”

mentioning

confidence: 99%