scholarly journals Superinfection Exclusion by p28 of Turnip Crinkle Virus Is Separable from Its Replication Function

2020 ◽  
Vol 33 (2) ◽  
pp. 364-375
Author(s):  
Qin Guo ◽  
Shaoyan Zhang ◽  
Rong Sun ◽  
Xiaolong Yao ◽  
Xiao-Feng Zhang ◽  
...  
Keyword(s):  
Amino Acid ◽  
Single Amino Acid ◽  
Turnip Crinkle Virus ◽  
Superinfection Exclusion ◽  
Protein Levels ◽  
Severe Reduction ◽  
Amino Acid Mutations ◽  
Concentration Threshold ◽  
Replication Function

We recently reported that the p28 auxiliary replication protein encoded by turnip crinkle virus (TCV) is also responsible for eliciting superinfection exclusion (SIE) against superinfecting TCV. However, it remains unresolved whether the replication function of p28 could be separated from its ability to elicit SIE. Here, we report the identification of two single amino acid mutations that decouple these two functions. Using an Agrobacterium infiltration-based delivery system, we transiently expressed a series of p28 deletion and point mutants, and tested their ability to elicit SIE against a cointroduced TCV replicon. We found that substituting alanine (A) for valine (V) and phenylalanine (F) at p28 positions 181 and 182, respectively, modestly compromised SIE in transiently expressed p28 derivatives. Upon incorporation into TCV replicons, V181A and F182A decoupled TCV replication and SIE diametrically. Although V181A impaired SIE without detectably compromising replication, F182A abolished TCV replication but had no effect on SIE once the replication of the defective replicon was restored through complementation. Both mutations diminished accumulation of p28 protein, suggesting that p28 must reach a concentration threshold in order to elicit a strong SIE. Importantly, the severe reduction of F182A protein levels correlated with a dramatic loss in the number of intracellular p28 foci formed by p28–p28 interactions. Together, these findings not only decouple the replication and SIE functions of p28 but also unveil a concentration dependence for p28 coalescence and SIE elicitation. These data further highlight the role of p28 multimerization in driving the exclusion of secondary TCV infections.

scholarly journals Elicitation of superinfection exclusion by p28 of turnip crinkle virus is separable from its replication function with mutations at specific amino acid residues

2019 ◽  
Author(s):  
Qin Guo ◽  
Shaoyan Zhang ◽  
Rong Sun ◽  
Xiaolong Yao ◽  
Xiao-Feng Zhang ◽  
...  
Keyword(s):  
Amino Acid ◽  
Single Amino Acid ◽  
Amino Acid Residues ◽  
Turnip Crinkle Virus ◽  
Virus Infections ◽  
Superinfection Exclusion ◽  
Protein Levels ◽  
Infected Cells ◽  
Concentration Threshold ◽  
Replication Function

ABSTRACTWe recently reported that the p28 auxiliary replication protein encoded by turnip crinkle virus (TCV) is also responsible for eliciting superinfection exclusion (SIE) against superinfecting TCV. However, it remains unresolved whether the replication function of p28 could be separated from its ability to elicit SIE. Here we report the identification of two single amino acid (aa) mutations that decouple these two functions. Using an Agrobacterium infiltration-based delivery system, we transiently expressed a series of p28 deletion and point mutants, and tested their ability to elicit SIE against a co-introduced TCV replicon. We found that substituting alanine (A) for valine (V) and phenylalanine (F) at p28 positions 181 and 182, respectively, modestly compromised SIE in transiently expressed p28 derivatives. Upon incorporation into TCV replicons, V181A and F182A decoupled TCV replication and SIE diametrically. While V181A impaired SIE without detectably compromising replication, F182A abolished TCV replication but had no effect on SIE once the replication of the defective replicon was restored through complementation. Both mutations diminished accumulation of p28 protein, suggesting that p28 must reach a concentration threshold in order to elicit a strong SIE. Importantly, the severe reduction of F182A protein levels correlated with a dramatic loss in the number of intracellular p28 foci formed by p28-p28 interactions. Together these findings not only decouples the replication and SIE functions of p28, but also unveils a concentration dependence for p28 coalescence and SIE elicitation. These data further highlight the role of p28 multimerization in driving the exclusion of secondary TCV infections.IMPORTANCESuperinfection exclusion (SIE) insulates virus-infected cells from subsequent invasion by the same or closely related viruses. SIE has been observed in both animal and plant virus-infected cells. Therefore, a thorough understanding of how SIE is achieved at the molecular level is expected to inspire novel strategies for combating virus infections in humans, animals, and plants. Our group has been using turnip crinkle virus (TCV) to elucidate the molecular interactions critical for SIE elicitation. The current study builds on the previous observation that TCV SIE is elicited by one single TCV-encoded protein (p28), and further identifies key regions and amino acids that are needed for SIE. We unravel key amino acid changes that decouple the replication and SIE functions of p28, and provides novel mechanistic insights of SIE.

scholarly journals Genetic Variation and Evolution of the 2019 Novel Coronavirus

2021 ◽  
pp. 1-13
Author(s):  
Salvatore Dimonte ◽  
Muhammed Babakir-Mina ◽  
Taib Hama-Soor ◽  
Salar Ali
Keyword(s):  
Amino Acid ◽  
Receptor Binding ◽  
Rapid Evolution ◽  
Single Amino Acid ◽  
Angiotensin Converting Enzyme 2 ◽  
New Type ◽  
Amino Acid Mutations ◽  
Host Infection ◽  
Human Coronaviruses ◽  
Novel Coronavirus

<b><i>Introduction:</i></b> SARS-CoV-2 is a new type of coronavirus causing a pandemic severe acute respiratory syndrome (SARS-2). Coronaviruses are very diverting genetically and mutate so often periodically. The natural selection of viral mutations may cause host infection selectivity and infectivity. <b><i>Methods:</i></b> This study was aimed to indicate the diversity between human and animal coronaviruses through finding the rate of mutation in each of the spike, nucleocapsid, envelope, and membrane proteins. <b><i>Results:</i></b> The mutation rate is abundant in all 4 structural proteins. The most number of statistically significant amino acid mutations were found in spike receptor-binding domain (RBD) which may be because it is responsible for a corresponding receptor binding in a broad range of hosts and host selectivity to infect. Among 17 previously known amino acids which are important for binding of spike to angiotensin-converting enzyme 2 (ACE2) receptor, all of them are conservative among human coronaviruses, but only 3 of them significantly are mutated in animal coronaviruses. A single amino acid aspartate-454, that causes dissociation of the RBD of the spike and ACE2, and F486 which gives the strength of binding with ACE2 remain intact in all coronaviruses. <b><i>Discussion/Conclusion:</i></b> Observations of this study provided evidence of the genetic diversity and rapid evolution of SARS-CoV-2 as well as other human and animal coronaviruses.

Structural assessment of single amino acid mutations: application to TP53 function

2006 ◽  
Vol 27 (9) ◽  
pp. 926-937 ◽  
Author(s):  
Yum L. Yip ◽  
Vincent Zoete ◽  
Holger Scheib ◽  
Olivier Michielin
Keyword(s):  
Amino Acid ◽  
Single Amino Acid ◽  
Structural Assessment ◽  
Amino Acid Mutations

scholarly journals Interleukin-37 monomer is the active form for reducing innate immunity

2019 ◽  
Vol 116 (12) ◽  
pp. 5514-5522 ◽  
Author(s):  
Elan Z. Eisenmesser ◽  
Adrian Gottschlich ◽  
Jasmina S. Redzic ◽  
Natasia Paukovich ◽  
Jay C. Nix ◽  
...  
Keyword(s):  
Active Form ◽  
Cell Types ◽  
Single Amino Acid ◽  
Integrative Approach ◽  
Heparin Binding ◽  
Protein Levels ◽  
Markers Of Inflammation ◽  
Biological Studies ◽  
Self Association ◽  
Amino Acid Mutations

Interleukin-37 (IL-37), a member of the IL-1 family of cytokines, is a fundamental suppressor of innate and acquired immunities. Here, we used an integrative approach that combines biophysical, biochemical, and biological studies to elucidate the unique characteristics of IL-37. Our studies reveal that single amino acid mutations at the IL-37 dimer interface that result in the stable formation of IL-37 monomers also remain monomeric at high micromolar concentrations and that these monomeric IL-37 forms comprise higher antiinflammatory activities than native IL-37 on multiple cell types. We find that, because native IL-37 forms dimers with nanomolar affinity, higher IL-37 only weakly suppresses downstream markers of inflammation whereas lower concentrations are more effective. We further show that IL-37 is a heparin binding protein that modulates this self-association and that the IL-37 dimers must block the activity of the IL-37 monomer. Specifically, native IL-37 at 2.5 nM reduces lipopolysaccharide (LPS)-induced vascular cell adhesion molecule (VCAM) protein levels by ∼50%, whereas the monomeric D73K mutant reduced VCAM by 90% at the same concentration. Compared with other members of the IL-1 family, both the N and the C termini of IL-37 are extended, and we show they are disordered in the context of the free protein. Furthermore, the presence of, at least, one of these extended termini is required for IL-37 suppressive activity. Based on these structural and biological studies, we present a model of IL-37 interactions that accounts for its mechanism in suppressing innate inflammation.

scholarly journals Mutations in Plasmodium falciparumCytochrome b That Are Associated with Atovaquone Resistance Are Located at a Putative Drug-Binding Site

2000 ◽  
Vol 44 (8) ◽  
pp. 2100-2108 ◽  
Author(s):  
Michael Korsinczky ◽  
Nanhua Chen ◽  
Barbara Kotecka ◽  
Allan Saul ◽  
Karl Rieckmann ◽  
...  
Keyword(s):  
Amino Acid ◽  
Binding Site ◽  
Point Mutations ◽  
Drug Binding ◽  
Single Amino Acid ◽  
Malaria Parasites ◽  
Drug Binding Site ◽  
Sole Agent ◽  
Amino Acid Mutations

ABSTRACT Atovaquone is the major active component of the new antimalarial drug Malarone. Considerable evidence suggests that malaria parasites become resistant to atovaquone quickly if atovaquone is used as a sole agent. The mechanism by which the parasite develops resistance to atovaquone is not yet fully understood. Atovaquone has been shown to inhibit the cytochrome bc 1 (CYTbc 1) complex of the electron transport chain of malaria parasites. Here we report point mutations in Plasmodium falciparum CYT b that are associated with atovaquone resistance. Single or double amino acid mutations were detected from parasites that originated from a cloned line and survived various concentrations of atovaquone in vitro. A single amino acid mutation was detected in parasites isolated from a recrudescent patient following atovaquone treatment. These mutations are associated with a 25- to 9,354-fold range reduction in parasite susceptibility to atovaquone. Molecular modeling showed that amino acid mutations associated with atovaquone resistance are clustered around a putative atovaquone-binding site. Mutations in these positions are consistent with a reduced binding affinity of atovaquone for malaria parasite CYTb.

scholarly journals SC-23 * THE ROLE OF SINGLE AMINO ACID POLYMORPHISMS IN GLIOMA STEM CELL PHENOTYPES

2014 ◽  
Vol 16 (suppl 5) ◽  
pp. v202-v202
Author(s):  
C. L. Nilsson ◽  
A. Vegvari ◽  
E. Mostovenko ◽  
C. F. Lichti ◽  
D. Fenyo ◽  
...  
Keyword(s):  
Stem Cell ◽  
Amino Acid ◽  
Single Amino Acid ◽  
Glioma Stem Cell ◽  
Single Amino Acid Polymorphisms ◽  
Cell Phenotypes

Single amino acid mutations ofMedicagoglycosyltransferase UGT85H2 enhance activity and impart reversibility

FEBS Letters ◽  
2009 ◽  
Vol 583 (12) ◽  
pp. 2131-2135 ◽  
Author(s):  
Luzia V. Modolo ◽  
Luis L. Escamilla-Treviño ◽  
Richard A. Dixon ◽  
Xiaoqiang Wang
Keyword(s):  
Amino Acid ◽  
Single Amino Acid ◽  
Amino Acid Mutations ◽  
Enhance Activity

scholarly journals Functional analysis of single amino-acid mutations in the thrombopoietin-receptor Mpl underlying congenital amegakaryocytic thrombocytopenia

2008 ◽  
Vol 141 (6) ◽  
pp. 808-813 ◽  
Author(s):  
Marloes R. Tijssen ◽  
Franca di Summa ◽  
Sonja van den Oudenrijn ◽  
Jaap Jan Zwaginga ◽  
C. Ellen van der Schoot ◽  
...  
Keyword(s):  
Functional Analysis ◽  
Amino Acid ◽  
Single Amino Acid ◽  
Thrombopoietin Receptor ◽  
Amino Acid Mutations

scholarly journals Ten emerging SARS-CoV-2 spike variants exhibit variable infectivity, animal tropism, and antibody neutralization

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Li Zhang ◽  
Zhimin Cui ◽  
Qianqian Li ◽  
Bo Wang ◽  
Yuanling Yu ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Amino Acid ◽  
Receptor Binding ◽  
Immune Escape ◽  
Cathepsin L ◽  
Single Amino Acid ◽  
Receptor Binding Domain ◽  
Therapeutic Antibodies ◽  
Amino Acid Mutations ◽  
Better Than

AbstractEmerging mutations in SARS-CoV-2 cause several waves of COVID-19 pandemic. Here we investigate the infectivity and antigenicity of ten emerging SARS-CoV-2 variants—B.1.1.298, B.1.1.7(Alpha), B.1.351(Beta), P.1(Gamma), P.2(Zeta), B.1.429(Epsilon), B.1.525(Eta), B.1.526-1(Iota), B.1.526-2(Iota), B.1.1.318—and seven corresponding single amino acid mutations in the receptor-binding domain using SARS-CoV-2 pseudovirus. The results indicate that the pseudovirus of most of the SARS-CoV-2 variants (except B.1.1.298) display slightly increased infectivity in human and monkey cell lines, especially B.1.351, B.1.525 and B.1.526 in Calu-3 cells. The K417N/T, N501Y, or E484K-carrying variants exhibit significantly increased abilities to infect mouse ACE2-overexpressing cells. The activities of furin, TMPRSS2, and cathepsin L are increased against most of the variants. RBD amino acid mutations comprising K417T/N, L452R, Y453F, S477N, E484K, and N501Y cause significant immune escape from 11 of 13 monoclonal antibodies. However, the resistance to neutralization by convalescent serum or vaccines elicited serum is mainly caused by the E484K mutation. The convalescent serum from B.1.1.7- and B.1.351-infected patients neutralized the variants themselves better than other SARS-CoV-2 variants. Our study provides insights regarding therapeutic antibodies and vaccines, and highlights the importance of E484K mutation.

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