Charged amino acid variability related to N-glyco -sylation and epitopes in A/H3N2 influenza: Hem -agglutinin and neuraminidase

ABSTRACT Plasmodium falciparum apical membrane antigen 1 (PfAMA1), a candidate malaria vaccine, is polymorphic. This polymorphism is believed to be generated predominantly under immune selection pressure and, as a result, may compromise attempts at vaccination. Alignment of 355 PfAMA1 sequences shows that around 10% of the 622 amino acid residues can vary between alleles and that linkages between polymorphic residues occur. Using this analysis, we have designed three diversity-covering (DiCo) PfAMA1 sequences that take account of these linkages and, when taken together, on average incorporate 97% of amino acid variability observed. For each of the three DiCo sequences, a synthetic gene was constructed and used to transform the methylotrophic yeast Pichia pastoris, allowing recombinant expression. All three DiCo proteins were reactive with the reduction-sensitive monoclonal antibody 4G2, suggesting the DiCo sequences had conformations similar to those of naturally occurring PfAMA1. Rabbits were immunized with FVO strain PfAMA1 or with the DiCo proteins either individually or as a mixture. Antibody titers and the ability to inhibit parasite growth in vitro were determined. Animals immunized with the DiCo mix performed similarly to animals immunized with FVO AMA1 when measured against FCR3 strain parasites but outperformed animals immunized with FVO AMA1 when assessed against other strains. The levels of growth inhibition (∼70%) induced by the mix of three DiCo proteins were comparable for FVO, 3D7, and HB3, suggesting that a considerable degree of diversity in AMA1 is adequately covered. This suggests that vaccines based upon the DiCo mix approach provide a broader functional immunity than immunization with a single allele.

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The degree of HIV-1 amino acid variability is strictly related to different disease progression rates

Virus Genes ◽

10.1007/s11262-018-1571-2 ◽

2018 ◽

Vol 54 (4) ◽

pp. 493-501 ◽

Cited By ~ 2

Author(s):

Rossana Scutari ◽

Monica Faieta ◽

Roberta D’Arrigo ◽

Lavinia Fabeni ◽

Cristina Mussini ◽

...

Keyword(s):

Amino Acid ◽

Disease Progression ◽

Amino Acid Variability ◽

Hiv 1

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Amino acid variability in the peptide composition of a suite of amphiphilic peptide siderophores from an open ocean Vibrio species

JBIC Journal of Biological Inorganic Chemistry ◽

10.1007/s00775-013-0995-3 ◽

2013 ◽

Vol 18 (5) ◽

pp. 489-497 ◽

Cited By ~ 18

Author(s):

Julia M. Gauglitz ◽

Alison Butler

Keyword(s):

Amino Acid ◽

Open Ocean ◽

Vibrio Species ◽

Amino Acid Variability ◽

Peptide Composition ◽

Amphiphilic Peptide

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A novel amino acid substitution at the receptor-binding site on the hemagglutinin of H3N2 influenza A viruses isolated from 6 cases with acute encephalopathy during the 1997–1998 season in Tokyo

Archives of Virology ◽

10.1007/s007050050491 ◽

1999 ◽

Vol 144 (1) ◽

pp. 147-155 ◽

Cited By ~ 16

Author(s):

S.-I. Mori ◽

M. Nagashima ◽

Y. Sasaki ◽

K. Mori ◽

Y. Tabei ◽

...

Keyword(s):

Amino Acid ◽

Binding Site ◽

Receptor Binding ◽

Amino Acid Substitution ◽

Influenza A ◽

Acute Encephalopathy ◽

Influenza A Viruses ◽

Receptor Binding Site ◽

H3n2 Influenza

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Identification and Characterization of DAMs Mutations Associated With Early Blooming in Sweet Cherry, and Validation of DNA-Based Markers for Selection

Frontiers in Plant Science ◽

10.3389/fpls.2021.621491 ◽

2021 ◽

Vol 12 ◽

Author(s):

Alejandro Calle ◽

Jérôme Grimplet ◽

Loïck Le Dantec ◽

Ana Wünsch

Keyword(s):

Amino Acid ◽

Candidate Genes ◽

Sweet Cherry ◽

Genomic Structure ◽

Chromosome 1 ◽

Change Scenario ◽

Pcr Markers ◽

Japanese Apricot ◽

Amino Acid Variability ◽

Structural Mutations

Dormancy release and bloom time of sweet cherry cultivars depend on the environment and the genotype. The knowledge of these traits is essential for cultivar adaptation to different growing areas, and to ensure fruit set in the current climate change scenario. In this work, the major sweet cherry bloom time QTL qP-BT1.1m (327 Kbs; Chromosome 1) was scanned for candidate genes in the Regina cv genome. Six MADS-box genes (PavDAMs), orthologs to peach and Japanese apricot DAMs, were identified as candidate genes for bloom time regulation. The complete curated genomic structure annotation of these genes is reported. To characterize PavDAMs intra-specific variation, genome sequences of cultivars with contrasting chilling requirements and bloom times (N = 13), were then mapped to the ‘Regina’ genome. A high protein sequence conservation (98.8–100%) was observed. A higher amino acid variability and several structural mutations were identified in the low-chilling and extra-early blooming cv Cristobalina. Specifically, a large deletion (694 bp) upstream of PavDAM1, and various INDELs and SNPs in contiguous PavDAM4 and -5 UTRs were identified. PavDAM1 upstream deletion in ‘Cristobalina’ revealed the absence of several cis-acting motifs, potentially involved in PavDAMs expression. Also, due to this deletion, a non-coding gene expressed in late-blooming ‘Regina’ seems truncated in ‘Cristobalina’. Additionally, PavDAM4 and -5 UTRs mutations revealed different splicing variants between ‘Regina’ and ‘Cristobalina’ PavDAM5. The results indicate that the regulation of PavDAMs expression and post-transcriptional regulation in ‘Cristobalina’ may be altered due to structural mutations in regulatory regions. Previous transcriptomic studies show differential expression of PavDAM genes during dormancy in this cultivar. The results indicate that ‘Cristobalina’ show significant amino acid differences, and structural mutations in PavDAMs, that correlate with low-chilling and early blooming, but the direct implication of these mutations remains to be determined. To complete the work, PCR markers designed for the detection of ‘Cristobalina’ structural mutations in PavDAMs, were validated in an F2 population and a set of cultivars. These PCR markers are useful for marker-assisted selection of early blooming seedlings, and probably low-chilling, from ‘Cristobalina’, which is a unique breeding source for these traits.

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Comparison of Genetic Variability at Multiple Loci across the Genomes of the Major Subtypes of Kaposi’s Sarcoma-Associated Herpesvirus Reveals Evidence for Recombination and for Two Distinct Types of Open Reading Frame K15 Alleles at the Right-Hand End

Journal of Virology ◽

10.1128/jvi.73.8.6646-6660.1999 ◽

1999 ◽

Vol 73 (8) ◽

pp. 6646-6660 ◽

Cited By ~ 145

Author(s):

Lynn J. Poole ◽

Jian-Chao Zong ◽

Dolores M. Ciufo ◽

Donald J. Alcendor ◽

Jennifer S. Cannon ◽

...

Keyword(s):

Amino Acid ◽

Kaposi's Sarcoma ◽

Human Herpesvirus ◽

Kaposi’S Sarcoma ◽

Amino Acid Identity ◽

Open Reading Frame ◽

Subtype C ◽

Reading Frame ◽

Right Hand ◽

Amino Acid Variability

ABSTRACT Kaposi’s sarcoma (KS)-associated herpesvirus or human herpesvirus 8 (HHV8) DNA is found consistently in nearly all classical, endemic, transplant, and AIDS-associated KS lesions, as well as in several AIDS-associated lymphomas. We have previously sequenced the genes for the highly variable open reading frame K1 (ORF-K1) protein from more than 60 different HHV8 samples and demonstrated that they display up to 30% amino acid variability and cluster into four very distinct evolutionary subgroups (the A, B, C, and D subtypes) that correlate with the major migrationary diasporas of modern humans. Here we have extended this type of analysis to six other loci across the HHV8 genome to further evaluate overall genotype patterns and the potential for chimeric genomes. Comparison of the relatively conserved ORF26, T0.7/K12, and ORF75 gene regions at map positions 0.35, 0.85, and 0.96 revealed typical ORF-K1-linked subtype patterns, except that between 20 and 30% of the genomes analyzed proved to be either intertypic or intratypic mosaics. In addition, a 2,500-bp region found at the extreme right-hand side of the unique segment in 45 HHV8 genomes proved to be highly diverged from the 3,500-bp sequence found at this position in the other 18 HHV8 genomes examined. Furthermore, these previously uncharacterized “orphan” region sequences proved to encompass multiexon latent-state mRNAs encoding two highly diverged alleles of the novel ORF-K15 protein. The predominant (P) and minor (M) forms of HHV8 ORF-K15 are structurally related integral membrane proteins that have only 33% overall amino acid identity to one another but retain conserved likely tyrosine kinase signaling motifs and may be distant evolutionary relatives of the LMP2 latency protein of Epstein-Barr virus. The M allele of ORF-K15 is also physically linked to a distinctive M subtype of the adjacent ORF75 gene locus, and in some cases, this linkage extends as far back as the T0.7 locus also. Overall, the results suggest that an original recombination event with a related primate virus from an unknown source introduced exogenous right-hand side ORF-K15(M) sequences into an ancient M form of HHV8, followed by eventual acquisition into the subtype C lineage of the modern P-form of the HHV8 genome and subsequent additional, more recent transfers by homologous recombination events into several subtype A and B lineages as well.

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