scholarly journals The V617I Substitution in Avian Coronavirus IBV Spike Protein Plays a Crucial Role in Adaptation to Primary Chicken Kidney Cells

2020 ◽  
Vol 11 ◽  
Author(s):  
Yi Jiang ◽  
Mingyan Gao ◽  
Xu Cheng ◽  
Yan Yu ◽  
Xinyue Shen ◽  
...  
Keyword(s):  
Amino Acid ◽  
Decisive Role ◽  
Virus Genome ◽  
Amino Acid Sequences ◽  
Cell Tropism ◽  
Recombinant Viruses ◽  
Infectious Bronchitis ◽  
Chicken Kidney ◽  
The Difference ◽  
S Genes

The naturally isolated avian coronavirus infectious bronchitis virus (IBV) generally cannot replicate in chicken kidney (CK) cells. To explore the molecular mechanism of IBV adapting to CK cells, a series of recombinant viruses were constructed by chimerizing the S genes of CK cell-adapted strain H120 and non-adapted strain IBYZ. The results showed that the S2 subunit determines the difference in cell tropism of the two strains. After comparing the amino acid sequences of S protein of CK cell-adapted strain YZ120, with its parental strain IBYZ, three amino acid substitutions, A138V, L581F, and V617I, were identified. Using YZ120 as the backbone, one or more of the above-mentioned substitutions were eliminated to verify the correlation between these sites and CK cell tropism. The results showed that the CK cell tropism of the YZ120 strain depends on the V617I substitution, the change of L581F promoted the adaptation in CK cells, and the change at 138 position was not directly related to the CK cell tropism. Further validation experiments also showed that V617I had a decisive role in the adaptation of IBV to CK cells, but other areas of the virus genome also affected the replication efficiency of the virus in CK cells.

scholarly journals Insertions and deletions trigger adaptive walks in Drosophila proteins

2012 ◽  
Vol 279 (1740) ◽  
pp. 3075-3082 ◽  
Author(s):  
Evgeny V. Leushkin ◽  
Georgii A. Bazykin ◽  
Alexey S. Kondrashov
Keyword(s):  
Amino Acid ◽  
Amino Acid Sequences ◽  
Molecular Adaptation ◽  
Amino Acid Substitutions ◽  
Protein Coding ◽  
Evolution Of Life ◽  
High Fraction ◽  
Adaptive Walks ◽  
The Difference ◽  
Almost All

Maps that relate all possible genotypes or phenotypes to fitness—fitness landscapes—are central to the evolution of life, but remain poorly known. An insertion or a deletion (indel) of one or several amino acids constitutes a substantial leap of a protein within the space of amino acid sequences, and it is unlikely that after such a leap the new sequence corresponds precisely to a fitness peak. Thus, one can expect an indel in the protein-coding sequence that gets fixed in a population to be followed by some number of adaptive amino acid substitutions, which move the new sequence towards a nearby fitness peak. Here, we study substitutions that occur after a frame-preserving indel in evolving proteins of Drosophila . An insertion triggers 1.03 ± 0.75 amino acid substitutions within the protein region centred at the site of insertion, and a deletion triggers 4.77 ± 1.03 substitutions within such a region. The difference between these values is probably owing to a higher fraction of effectively neutral insertions. Almost all of the triggered amino acid substitutions can be attributed to positive selection, and most of them occur relatively soon after the triggering indel and take place upstream of its site. A high fraction of substitutions that follow an indel occur at previously conserved sites, suggesting that an indel substantially changes selection that shapes the protein region around it. Thus, an indel is often followed by an adaptive walk of length that is in agreement with the theory of molecular adaptation.

scholarly journals Insights into the Selective Pressures Restricting Pelargonium Flower Break Virus Genome Variability: Evidence for Host Adaptation

2006 ◽  
Vol 80 (16) ◽  
pp. 8124-8132 ◽  
Author(s):  
Patricia Rico ◽  
Pilar Ivars ◽  
Santiago F. Elena ◽  
Carmen Hernández
Keyword(s):  
Amino Acid ◽  
Leucine Zipper ◽  
Critical Role ◽  
Chenopodium Quinoa ◽  
Virus Genome ◽  
Acid Sites ◽  
Genomic Region ◽  
Amino Acid Sequences ◽  
Nucleotide Substitutions ◽  
Selective Pressures

ABSTRACT The molecular diversity of Pelargonium flower break virus (PFBV) was assessed using a collection of isolates from different geographical origins, hosts, and collecting times. The genomic region examined was 1,828 nucleotides (nt) long and comprised the coding sequences for the movement (p7 and p12) and the coat (CP) proteins, as well as flanking segments including the entire 3′ untranslated region (3′ UTR). Some constraints limiting viral heterogeneity could be inferred from sequence analyses, such as the conservation of the amino acid sequences of p7 and of the shell domain of the CP, the maintenance of a leucine zipper motif in p12, and the preservation of a particular folding in the 3′ UTR. A remarkable covariation, involving five specific amino acid sites, was found in the CP of isolates largely propagated in the local lesion host Chenopodium quinoa and in the progeny of a PFBV variant subjected to serial passages in this host. Concomitant with this covariation, up to 30 nucleotide substitutions in a 1,428-nt region of the viral RNA could be attributable to C. quinoa-specific adaptation, representing one of the most outstanding cases of host-driven genome variation for a plant virus. Globally, the results indicate that the selective pressures exerted by the host play a critical role in shaping PFBV populations and that these populations are likely being selected for at both protein and RNA levels.

scholarly journals Supervised learning of protein thermal stability using sequence mining and distribution statistics of network centrality

2019 ◽  
Author(s):  
Ankit Sharma ◽  
Ganesh Bagler ◽  
Debajyoti Bera
Keyword(s):  
Thermal Stability ◽  
Amino Acid ◽  
Amino Acid Sequences ◽  
Molecular Structures ◽  
Network Centrality ◽  
Learning Approaches ◽  
Peptide Bonds ◽  
The Difference ◽  
Structural Networks ◽  
Feature Selection Techniques

AbstractMotivationIt is expected that the difference in the thermal stability of mesophilic and thermophilic proteins arises, in part at least, from the differences in their molecular structures and amino acid compositions. Existing machine learning approaches for supervised classification of proteins rely on the features derived from the structural networks and the amino acid sequences. However, the network features used leave out several important network centrality values, the statistic used is a simple average and the sequence features used are hand-picked leading to an accuracy of 90%.ResultsWe show that discriminating sub-sequences of the amino acid sequences can significantly improve classification accuracy compared to the existing approaches of counting amino acids, di-peptide or even tri-peptide bonds. We identify notions of network centrality, specifically that depends on the distances between Cα atoms, that appears to correlate better with thermal stability compared to the existing network features. We also show how to generate better statistics from the node- and edge-wise centrality values that more accurately captures the variations in their values for different types of proteins. These improved feature selection techniques make it possible to classify between thermophilic and mesophilic proteins with 96% accuracy and 99% area under ROC.AvailabilityThe dataset and source code used are available at https://github.com/ankits0207/[email protected].

scholarly journals Genetic Determinants of Sindbis Virus Mosquito Infection Are Associated with a Highly Conserved Alphavirus and Flavivirus Envelope Sequence

2007 ◽  
Vol 82 (6) ◽  
pp. 2966-2974 ◽  
Author(s):  
Dennis J. Pierro ◽  
Erik L. Powers ◽  
Ken E. Olson
Keyword(s):  
Amino Acid ◽  
Sindbis Virus ◽  
Virus Genome ◽  
Growth Patterns ◽  
Amino Acid Sequences ◽  
Genetic Determinants ◽  
Nucleotide Substitutions ◽  
Conserved Sequence ◽  
E2 Glycoprotein ◽  
Envelope Sequence

ABSTRACT Wild-type Sindbis virus (SINV) strain MRE16 efficiently infects Aedes aegypti midgut epithelial cells (MEC), but laboratory-derived neurovirulent SINV strain TE/5′2J infects MEC poorly. SINV determinants for MEC infection have been localized to the E2 glycoprotein. The E2 amino acid sequences of MRE16 and TE/5′2J differ at 60 residue sites. To identify the genetic determinants of MEC infection of MRE16, the TE/5′2J virus genome was altered to contain either domain chimeras or more focused nucleotide substitutions of MRE16. The growth patterns of derived viruses in cell culture were determined, as were the midgut infection rates (MIR) in A. aegypti mosquitoes. The results showed that substitutions of MRE16 E2 aa 95 to 96 and 116 to 119 into the TE/5′2J virus increased MIR both independently and in combination with each other. In addition, a unique PPF/.GDS amino acid motif was located between these two sites that was found to be a highly conserved sequence among alphaviruses and flaviviruses but not other arboviruses.

Activation of oncogenicity of the c-rel proto-oncogene

1986 ◽  
Vol 6 (12) ◽  
pp. 4709-4716
Author(s):  
B S Sylla ◽  
H M Temin
Keyword(s):  
Amino Acid ◽  
Virus Strain ◽  
Helper Virus ◽  
Amino Acid Sequences ◽  
Lymphoid Cells ◽  
Chimeric Proteins ◽  
Reticuloendotheliosis Virus ◽  
Recombinant Viruses ◽  
Transforming Gene

Reticuloendotheliosis virus strain T (Rev-T) induces a lethal lymphoma in young birds and transforms avian lymphoid cells in vitro. The transforming gene of Rev-T, v-rel, was derived from the turkey proto-oncogene c-rel. Comparison of the nucleotide sequences of v-rel and c-rel indicates that in addition to several internal amino acid changes relative to c-rel, p59v-rel has amino acid sequences at both ends derived from the reticuloendotheliosis virus strain A-related virus env gene (K. C. Wilhelmsen, K. Eggleton, and H. M. Temin, J. Virol. 52:172-182, 1984). In this report, the v-rel sequences important for transformation were defined by constructing recombinant retroviruses in which c-rel sequences replaced the analogous v-rel sequences. These recombinant viruses expressing chimeric proteins were tested for their ability to transform spleen cells in vitro and to induce tumors in young chickens. Activation of the oncogenicity of c-rel in Rev-T required alteration of the amino terminus and the central region of the protein. Deletion of the noncoding sequences 3' to c-rel and of most of the helper virus-related env sequences was necessary for the formation of Rev-T.

scholarly journals Evolution of the hepatitis E virus hypervariable region

2012 ◽  
Vol 93 (11) ◽  
pp. 2408-2418 ◽  
Author(s):  
Donald B. Smith ◽  
Jeff Vanek ◽  
Sandeep Ramalingam ◽  
Ingolfur Johannessen ◽  
Kate Templeton ◽  
...  
Keyword(s):  
Amino Acid ◽  
Positive Selection ◽  
Hepatitis E Virus ◽  
Hypervariable Region ◽  
Hepatitis E ◽  
Virus Genome ◽  
Amino Acid Sequences ◽  
Specific Sequence ◽  
Virus Genotypes ◽  
Selection For

The presence of a hypervariable (HVR) region within the genome of hepatitis E virus (HEV) remains unexplained. Previous studies have described the HVR as a proline-rich spacer between flanking functional domains of the ORF1 polyprotein. Others have proposed that the region has no function, that it reflects a hypermutable region of the virus genome, that it is derived from the insertion and evolution of host sequences or that it is subject to positive selection. This study attempts to differentiate between these explanations by documenting the evolutionary processes occurring within the HVR. We have measured the diversity of HVR sequences within acutely infected individuals or amongst sequences derived from epidemiologically linked samples and, surprisingly, find relative homogeneity amongst these datasets. We found no evidence of positive selection for amino acid substitution in the HVR. Through an analysis of published sequences, we conclude that the range of HVR diversity observed within virus genotypes can be explained by the accumulation of substitutions and, to a much lesser extent, through deletions or duplications of this region. All published HVR amino acid sequences display a relative overabundance of proline and serine residues that cannot be explained by a local bias towards cytosine in this part of the genome. Although all published HVRs contain one or more SH3-binding PxxP motifs, this motif does not occur more frequently than would be expected from the proportion of proline residues in these sequences. Taken together, these observations are consistent with the hypothesis that the HVR has a structural role that is dependent upon length and amino acid composition, rather than a specific sequence.

scholarly journals Identification of cytokine-induced neutrophil chemoattractants (CINC), rat GRO/CINC-2α and CINC-2 β, produced by granulation tissue in culture: purification, complete amino acid sequences and characterization

1994 ◽  
Vol 301 (2) ◽  
pp. 545-550 ◽  
Author(s):  
H Nakagawa ◽  
N Komorita ◽  
F Shibata ◽  
A Ikesue ◽  
K Konishi ◽  
...  
Keyword(s):  
Amino Acid ◽  
Amino Acid Sequence ◽  
Granulation Tissue ◽  
Pcr Amplification ◽  
Neutrophil Infiltration ◽  
Amino Acid Sequences ◽  
Terminal Amino Acid ◽  
Reverse Transcription Pcr ◽  
Terminal Amino ◽  
The Difference

Four basic neutrophil chemotactic factors (chemokines) have been purified from conditioned medium of granulation tissue obtained from carrageenin-induced inflammation in the rat. On the basis of their N-terminal amino acid sequences, one of the chemokines was identical with rat GRO/cytokine-induced neutrophil chemoattractant (CINC) which we reported previously, and another was identical with rat macrophage inflammatory protein-2 (MIP-2). Two other chemokines were novel chemoattractants related to MIP-2. The novel chemokines are referred to as rat GRO/CINC-2 alpha and CINC-2 beta, and consequently CINC and rat MIP-2 are renamed rat GRO/CINC-1 and CINC-3 respectively. The complete amino acid sequences of purified CINC-2 alpha and CINC-3 were determined by analysis of the fragments isolated from proteinase V8-treated CINCs. The cDNA for CINC-2 beta was cloned by reverse transcription/PCR amplification using specific primers starting with total RNA extracted from lipopolysaccharide-stimulated rat macrophages. A comparison of the amino acid sequence encoded by the cDNA with the N-terminal amino acid sequence of purified CINC-2 beta revealed that mature CINC-2 beta is a 68-residue chemoattractant produced by cleavage of a 32-residue signal peptide. The difference in amino acid sequences between CINC-2 alpha and CINC-2 beta consisted of only three C-terminal residues. Rat GRO/CINC-2 alpha is a major chemokine, and the four purified chemokines have similar chemotactic activity, suggesting that they contribute to neutrophil infiltration into inflammatory sites in rats.

scholarly journals Suboptimal Nucleotides in the Infectious, Pathogenic Simian Immunodeficiency Virus Clone SIVmac239

2001 ◽  
Vol 75 (8) ◽  
pp. 4019-4022 ◽  
Author(s):  
Louis Alexander ◽  
Lynn Denekamp ◽  
Susan Czajak ◽  
Ronald C. Desrosiers
Keyword(s):  
Amino Acid ◽  
Simian Immunodeficiency Virus ◽  
High Viral Load ◽  
Virus Genome ◽  
Amino Acid Sequences ◽  
Primer Binding Site ◽  
Nucleotide Change ◽  
Single Nucleotide ◽  
Single Nucleotide Change ◽  
Immunodeficiency Virus

ABSTRACT We analyzed virus sequences in two monkeys infected with SIVmac239 and two monkeys infected with SHIVnef that maintained high, persisting viral loads. Sequence changes were observed consistently at four loci in all four animals: a single nucleotide change in the Lys-tRNA primer binding site in the 5′ long terminal repeat; two nucleotide changes that resulted in two amino acid changes in thepol gene product; and a single nucleotide change in the region of the simian immunodeficiency virus genome where therev and env genes overlap, resulting in changes in the predicted amino acid sequences of both gene products. None of these mutations were seen in short-term cultures of CEM×174 cells infected with SIVmac239 or SHIVnef. At all four positions in all four animals, the new sequences represented consensus sequences for primate lentiviruses, whereas the inoculum sequences at these four loci have either never been or rarely been reported outside of SIVmac239. Thus, although cloned SIVmac239 is consistently pathogenic and consistently induces high viral load set points, it is clearly less than optimal at these four nucleotide positions.

The Difference in the Carboxy-Terminal Sequence Is Responsible for the Difference in the Activity of Chicken and Rat Liver Fructose-2,6-Bisphosphatase

2000 ◽  
Vol 381 (12) ◽  
pp. 1195-1202 ◽  
Author(s):  
Zheng Zhu ◽  
Song Ling ◽  
Qi-Heng Yang ◽  
Lin Li
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Liver Enzyme ◽  
Rat Liver ◽  
Amino Acid Sequences ◽  
Kinetic Properties ◽  
Catalytic Core ◽  
Bifunctional Enzymes ◽  
The Difference ◽  
Carboxy Terminal

Abstract The fructose-2,6-bisphosphatase domain of the bifunctional chicken liver enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase shares approximately 95% amino acid sequence homology with that of the rat enzyme. However, these two enzymes are significantly different in their phosphatase activities. In this report, we show that the COOH-terminal 25 amino acids of the two enzymes are responsible for the different enzymatic activities. Although these 25 amino acids are not required for the phosphatase activity, their removal diminishes the differences in the activities between the two enzymes. In addition, two chimeric molecules (one consisting of the catalytic core of the chicken bisphosphatase domain and the rat COOH-terminal 25 amino acids, and the other consisting of most of the intact chicken enzyme and the rat COOH-terminal 25 amino acids) showed the same kinetic properties as the rat enzyme. Furthermore, substitution of the residues Pro456pro457Ala458 of the chicken enzyme with GluAlaGlu, the corresponding sequence in the rat liver enzyme, yields a chicken enzyme that behaves like the rat enzyme. These results demonstrate that the different bisphosphatase activities of the chicken and rat liver bifunctional enzymes can be attributed to the differences in their COOH-terminal amino acid sequences, particularly the three residues.

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