&lt;p&gt;Virus–Receptor Interactions: Structural Insights For Oncolytic Virus Development&lt;/p&gt;

Jayawardena, Nadishka; Burga, Laura N.; Poirier, John T.; Bostina, Mihnea

doi:10.2147/ov.s218494

Cited by 30 publications

(23 citation statements)

References 252 publications

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“…1f, g). In general, functional receptor attachment is capable of dissociating viral capsid protein interactions to trigger genome release 3,16,17,29,30 . However, both intact antibodies and Fab fragments of 6C5 and 4B10 destabilized slightly E30 virions by 1-3°C ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Such strategy, however, has not yet been explored for EV-Bs. It is well known that many picornaviruses utilize two types of receptors, attachment and uncoating, to initiate efficient cellular entry processes, including viral attachment, endocytosis, internalization, uncoating and genome release [see coordinated submission by Wang et al 15 ] 16,17 . These processes are generally accompanied by a cascade of structural rearrangements of viral capsid proteins initiated and mediated by receptor binding as well as specific microenvironments [see coordinated submission by Wang et al 15 ] 6,[18][19][20][21][22][23][24][25][26] .…”

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confidence: 99%

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Serotype specific epitopes identified by neutralizing antibodies underpin immunogenic differences in Enterovirus B

et al. 2020

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Echovirus 30 (E30), a serotype of Enterovirus B (EV-B), recently emerged as a major causative agent of aseptic meningitis worldwide. E30 is particularly devastating in the neonatal population and currently no vaccine or antiviral therapy is available. Here we characterize two highly potent E30-specific monoclonal antibodies, 6C5 and 4B10, which efficiently block binding of the virus to its attachment receptor CD55 and uncoating receptor FcRn. Combinations of 6C5 and 4B10 augment the sum of their individual anti-viral activities. Highresolution structures of E30-6C5-Fab and E30-4B10-Fab define the location and nature of epitopes targeted by the antibodies. 6C5 and 4B10 engage the capsid loci at the north rim of the canyon and in-canyon, respectively. Notably, these regions exhibit antigenic variability across EV-Bs, highlighting challenges in development of broad-spectrum antibodies. Our structures of these neutralizing antibodies of E30 are instructive for development of vaccines and therapeutics against EV-B infections.

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Section: Resultsmentioning

confidence: 99%

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confidence: 99%

Serotype specific epitopes identified by neutralizing antibodies underpin immunogenic differences in Enterovirus B

et al. 2020

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“…ACE2 has also been proven to be a major receptor of the novel 2019-nCoV because 2019-nCoV is closely related to SARS-CoV. As the virus enters the cell by binding to cell receptors to complete intracellular replication, virus release, and induce cytotoxicity, the route of virus infection depends on the expression and distribution of the corresponding receptor [10][11][12]. Meanwhile, the damage caused by the virus in different organs is closely related to clinical manifestations and has a major implication for understanding the pathogenesis and designing therapeutic strategies in clinical practice.…”

Section: Introductionmentioning

confidence: 99%

ACE2 Expression in Kidney and Testis May Cause Kidney and Testis Damage After 2019-nCoV Infection

Fan

Ding

et al. 2020

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322

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In December 2019 and January 2020, novel coronavirus (2019-nCoV) -infected pneumonia (NCIP) occurred in Wuhan, and has already posed a serious threat to public health. ACE2 (Angiotensin Converting Enzyme 2) has been shown to be one of the major receptors that mediate the entry of 2019-nCoV into human cells, which also happens in severe acute respiratory syndrome coronavirus (SARS). Several researches have indicated that some patients have abnormal renal function or even kidney damage in addition to injury in respiratory system, and the related mechanism is unknown. This arouses our interest in whether coronavirus infection will affect the urinary and male reproductive systems. Here in this study, we used the online datasets to analyze ACE2 expression in different human organs. The results indicate that ACE2 highly expresses in renal tubular cells, Leydig cells and cells in seminiferous ducts in testis. Therefore, virus might directly bind to such ACE2 positive cells and damage the kidney and testicular tissue of patients. Our results indicate that renal function evaluation and special care should be performed in 2019-nCoV patients during clinical work, because of the kidney damage caused by virus and antiviral drugs with certain renal toxicity. In addition, due to the potential pathogenicity of the virus to testicular tissues, clinicians should pay attention to the risk of testicular lesions in patients during hospitalization and later clinical follow-up, especially the assessment and appropriate intervention in young patients' fertility.

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“…EV-Bs share the same overall structure found in other picornaviruses with a~7.5 kb single-stranded positive-sense RNA genome that encodes four viral protein subunits VP1-4, 60 copies of which assemble into a pseudo T = 3 icosahedral capsid 20 . While VP1-3 interact with each other to construct the outer architecture of the viral capsid, their N-termini, together with VP4, line the interior.…”

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confidence: 96%

Structures of Echovirus 30 in complex with its receptors inform a rational prediction for enterovirus receptor usage

et al. 2020

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Receptor usage that determines cell tropism and drives viral classification closely correlates with the virus structure. Enterovirus B (EV-B) consists of several subgroups according to receptor usage, among which echovirus 30 (E30), a leading causative agent for human aseptic meningitis, utilizes FcRn as an uncoating receptor. However, receptors for many EVs remain unknown. Here we analyzed the atomic structures of E30 mature virion, empty-and A-particles, which reveals serotype-specific epitopes and striking conformational differences between the subgroups within EV-Bs. Of these, the VP1 BC loop markedly distinguishes E30 from other EV-Bs, indicative of a role as a structural marker for EV-B. By obtaining cryoelectron microscopy structures of E30 in complex with its receptor FcRn and CD55 and comparing its homologs, we deciphered the underlying molecular basis for receptor recognition. Together with experimentally derived viral receptor identifications, we developed a structure-based in silico algorithm to inform a rational prediction for EV receptor usage.

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<p>Virus–Receptor Interactions: Structural Insights For Oncolytic Virus Development</p>

Cited by 30 publications

References 252 publications

Serotype specific epitopes identified by neutralizing antibodies underpin immunogenic differences in Enterovirus B

Serotype specific epitopes identified by neutralizing antibodies underpin immunogenic differences in Enterovirus B

ACE2 Expression in Kidney and Testis May Cause Kidney and Testis Damage After 2019-nCoV Infection

Structures of Echovirus 30 in complex with its receptors inform a rational prediction for enterovirus receptor usage

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