scholarly journals Evolution of Human Calicivirus RNA In Vivo:Accumulation of Mutations in the Protruding P2 Domain of the CapsidLeads to Structural Changes and Possibly a NewPhenotype

2003 ◽  
Vol 77 (24) ◽  
pp. 13117-13124 ◽  
Author(s):  
Mikael Nilsson ◽  
Kjell-Olof Hedlund ◽  
Margareta Thorhagen ◽  
Göran Larson ◽  
Kari Johansen ◽  
...  
Keyword(s):  
Amino Acid ◽  
Gene Polymorphism ◽  
Structural Changes ◽  
Clinical Symptoms ◽  
Viral Evolution ◽  
Comparative Sequence Analysis ◽  
Single Individual ◽  
Gene Characterization ◽  
Viral Shedding ◽  
Immune Pressure

ABSTRACT In the present study we report on evolution of calicivirus RNA from a patient with chronic diarrhea (i.e., lasting >2 years) and viral shedding. Partial sequencing of open reading frame 1 (ORF1) from 12 consecutive isolates revealed shedding of a genogroup II virus with relatively few nucleotide changes during a 1-year period. The entire capsid gene (ORF2) was also sequenced from the same isolates and found to contain 1,647 nucleotides encoding a protein of 548 amino acids with similarities to the Arg320 and Mx strains. Comparative sequence analysis of ORF2 revealed 32 amino acid changes during the year. It was notable that the vast majority of the cumulative amino acid changes (8 of 11) appeared within residues 279 to 405 located within the hypervariable domain (P2) of the capsid protein and hence were subject to immune pressure. An interesting and novel observation was that the accumulated amino acid changes in the P2 domain resulted in predicted structural changes, including disappearance of a helix structure, and thus a possible emergence of a new phenotype. FUT2 gene polymorphism characterization revealed that the patient is heterozygous at nucleotide 428 and thus Secretor+, a finding in accordance with the hypothesis of FUT2 gene polymorphism and calicivirus susceptibility. To our knowledge, this is the first report of RNA evolution of calicivirus in a single individual, and our data suggest an immunity-driven mechanism for viral evolution. We also report on chronic virus excretion, immunoglobulin treatment, and modification of clinical symptoms; our observations from these studies, together with the FUT2 gene characterization, may lead to a better understanding of calicivirus pathogenesis.

scholarly journals Origin and Evolution Analysis and Genetic Characteristics of Echovirus 9 in China

2021 ◽  
Author(s):  
Fenfen SI ◽  
Tianjiao JI ◽  
Dongyan WANG ◽  
Yong ZHANG ◽  
Shuangli ZHU ◽  
...  
Keyword(s):  
Amino Acid ◽  
Clinical Symptoms ◽  
Viral Evolution ◽  
Amino Acid Identity ◽  
Whole Genome Sequence ◽  
Temperature Sensitive ◽  
Time Resolved ◽  
Genetic Characteristics ◽  
Geographic Population ◽  
Origin And Evolution

Abstract BackgroundEchovirus 9 (E9) is associated with a wide variety of diseases and medical conditions, and the clinical symptoms of sporadic cases caused by E9 often are severe. With a high global prevalence, E9 has caused multiple outbreaks worldwide. However, little is known about the genetic and geographic population dynamics of E9.MethodA total of 131 VP1 gene sequences, including15 generated in this study and 116 obtained from GenBank, were used to coestimate time-resolved phylogenies to infer viral evolution and transmission in worldwide. Overlapping fragments representing whole genomes were amplified by reverse transcription polymerase chain reaction (RT-PCR) using specific primers. Then, we reported the genetic characteristics of fifteen E9 strains in the Chinese Mainland. Similarity plots and bootscanning analysis were used to determine recombination patterns of E9.ResultsThe estimated mean evolutionary rate of global E9 VP1 gene was 4.278 × 10−3 substitutions per site per year (95% confidence interval [CI], 3.822× 10−3/site/year to 4.710× 10−3/site/year), and the common ancestor of E9 likely emerged around 1868 (95% CI, 1840 to 1892). The full-length genomic sequences of the fifteen E9 strains showed 76.9-79.6% nucleotide identity and 95.3–95.9% amino acid identity with E9 Barty strain. 11 of 15 E9 whole genome sequence present four recombination patterns, and E9 recombinants have extensive genetic exchanges in the 2C and P3 regions with other Enterovirus B (EV-B) circulated in China. Four of six E9 strains were temperature sensitive, and two were temperature resistant, and a comparative genomics analysis suggested that 411, 865 and 867 amino acid substitution in the P1 region was related to temperature sensitivity.ConclusionThis study highlights a persistent transmission network of E9 in worldwide, provides valuable information regarding the molecular epidemiology of E9.

Paris I Dysfibrinogenemia: A Point Mutation in Intron 8 Results in Insertion of a 15 Amino Acid Sequence in the Fibrinogen γ-Chain

1993 ◽  
Vol 69 (03) ◽  
pp. 217-220 ◽  
Author(s):  
Jonathan B Rosenberg ◽  
Peter J Newman ◽  
Michael W Mosesson ◽  
Marie-Claude Guillin ◽  
David L Amrani
Keyword(s):  
Amino Acid ◽  
Amino Acid Sequence ◽  
Point Mutation ◽  
Genomic Dna ◽  
Comparative Sequence Analysis ◽  
Chain Gene ◽  
Molecular Defect ◽  
Nucleotide Position ◽  
Normal Individuals ◽  
Polymerase Chain

SummaryParis I dysfibrinogenemia results in the production of a fibrinogen molecule containing a functionally abnormal γ-chain. We determined the basis of the molecular defect using polymerase chain reaction (PCR) to amplify the γ-chain region of the Paris I subject’s genomic DNA. Comparative sequence analysis of cloned PCR segments of normal and Paris I genomic DNA revealed only an A→G point mutation occurring at nucleotide position 6588 within intron 8 of the Paris I γ-chain gene. We examined six normal individuals and found only normal sequence in this region, indicating that this change is not likely to represent a normal polymorphism. This nucleotide change leads to a 45 bp fragment being inserted between exons 8 and 9 in the mature γparis I chain mRNA, and encodes a 15 amino acid insert after γ350 [M-C-G-E-A-L-P-M-L-K-D-P-C-Y]. Alternative splicing of this region from intron 8 into the mature Paris I γ-chain mRNA also results after translation into a substitution of S for G at position γ351. Biochemical studies of 14C-iodoacetamide incorporation into disulfide-reduced Paris I and normal fibrinogen corroborated the molecular biologic predictions that two additional cysteine residues exist within the γpariS I chain. We conclude that the insertion of this amino acid sequence leads to a conformationallyaltered, and dysfunctional γ-chain in Paris I fibrinogen.

scholarly journals Clinical characteristics and outcomes of COVID-19 long-term nucleic acid positive patients

2021 ◽  
pp. 1-10
Author(s):  
Xuan Zhu ◽  
Xinxin Zhu ◽  
Min Wang ◽  
Fang Yang ◽  
Zhibing Sun ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Clinical Characteristics ◽  
Clinical Symptoms ◽  
Control Group ◽  
Viral Shedding ◽  
Imaging Characteristics ◽  
And Gender ◽  
Acid Test ◽  
Pulmonary Ct

OBJECTIVE: This study aimed to investigate the clinical characteristics and outcomes of coronavirus disease-19 (COVID-19) long-term nucleic acid positive patients (hereinafter referred to as CLTAPs). METHODS: Patients were recruited from the Xiaogan Central Hospital between 16 January 2020 and 28 March 2020. Among the 562 cases of patients with laboratory-identified COVID-19 infection by real-time polymerase chain reaction (qtPCR), 19 cases of COVID-19 patients with more than 41 days from the first to the last time of nucleic acid test were selected as the study group, and 76 cases of age- and gender-matched COVID-19 patients were selected as the control group (hereinafter referred to as C-CLTAPs). Demographic characteristics, clinical symptoms, laboratory examination and computed tomography (CT) imaging characteristics were retrospectively analyzed. RESULTS: On admission, among the 562 cases of patients with COVID-19, there were 398 cases of ordinary COVID-19 patients, 99 cases of severe COVID-19 patients and 99 cases of critical COVID-19 patients. CLTAPs had milder clinical symptoms and longer viral shedding time in comparison to C-CLTAPs. Compared to C-CLTAPs, CLTAPs had a lower infection index at admission. CLTAPs used less oxygen therapy and a higher proportion of hydroxychloroquine treatment in comparison to C-CLTAPs. In comparison to C-CLTAPs, CLTAPs showed slower pulmonary CT progression and faster pulmonary CT absorption. CONCLUSION: In this study, out of the 562 cases, we found 19 CLTAPs. The clinical differences between CLTAPs and C-CLTAPs were compared and analyzed. We hope that these finding can provide a theoretical basis for the treatment of CLTAPs.

scholarly journals Genetic and Antigenic Characterization of Avian Avulavirus Type 6 (AAvV-6) Circulating in Canadian Wild Birds (2005–2017)

Viruses ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 543
Author(s):  
Tamiko Hisanaga ◽  
Catherine Soos ◽  
Nicola Lewis ◽  
Oliver Lung ◽  
Matthew Suderman ◽  
...  
Keyword(s):  
Clinical Symptoms ◽  
Fusion Gene ◽  
Full Genome ◽  
Genome Sequences ◽  
Viral Shedding ◽  
Genetic Groups ◽  
Antigenic Characterization ◽  
Specific Pathogen ◽  
First Time

We describe for the first time the genetic and antigenic characterization of 18 avian avulavirus type-6 viruses (AAvV-6) that were isolated from wild waterfowl in the Americas over the span of 12 years. Only one of the AAvV-6 viruses isolated failed to hemagglutinate chicken red blood cells. We were able to obtain full genome sequences of 16 and 2 fusion gene sequences from the remaining 2 isolates. This is more than double the number of full genome sequences available at the NCBI database. These AAvV-6 viruses phylogenetically grouped into the 2 existing AAvV-6 genotype subgroups indicating the existence of an intercontinental epidemiological link with other AAvV-6 viruses isolated from migratory waterfowl from different Eurasian countries. Antigenic maps made using HI assay data for these isolates showed that the two genetic groups were also antigenically distinct. An isolate representing each genotype was inoculated in specific pathogen free (SPF) chickens, however, no clinical symptoms were observed. A duplex fusion gene based real-time assay for the detection and genotyping of AAvV-6 to genotype 1 and 2 was developed. Using the developed assay, the viral shedding pattern in the infected chickens was examined. The chickens infected with both genotypes were able to shed the virus orally for about a week, however, no significant cloacal shedding was detected in chickens of both groups. Chickens in both groups developed detectable levels of anti-hemagglutinin antibodies 7 days after infection.

scholarly journals Cloning, post-translational modifications, heterologous expression and ligand-binding of boar salivary lipocalin

2000 ◽  
Vol 350 (2) ◽  
pp. 369-379 ◽  
Author(s):  
Dietrich LOEBEL ◽  
Andrea SCALONI ◽  
Sara PAOLINI ◽  
Carlo FINI ◽  
Lino FERRARA ◽  
...  
Keyword(s):  
Amino Acid ◽  
Sequence Similarity ◽  
Three Dimensional ◽  
Protein Isoforms ◽  
Cysteine Residues ◽  
Protein Chemistry ◽  
Single Individual ◽  
Amino Acid Residues ◽  
Three Dimensional Model ◽  
Submaxillary Glands

Boar submaxillary glands produce the sex-specific salivary lipocalin (SAL), which binds steroidal sex pheromones as endogenous ligands. The cDNA encoding SAL was cloned and sequenced. From a single individual, two protein isoforms, differing in three amino acid residues, were purified and structurally characterized by a combined Edman degradation/MS approach. These experiments ascertained that the mature polypeptide is composed of 168 amino acid residues, that one of the three putative glycosylation sites is post-translationally modified and the structure of the bound glycosidic moieties. Two of the cysteine residues are paired together in a disulphide bridge, whereas the remaining two occur as free thiols. SAL bears sequence similarity to other lipocalins; on this basis, a three-dimensional model of the protein has been built. A SAL isoform was expressed in Escherichiacoli in good yields. Protein chemistry and CD experiments verified that the recombinant product shows the same redox state at the cysteine residues and that the same conformation is observed as in the natural protein, thus suggesting similar folding. Binding experiments on natural and recombinant SAL were performed with the fluorescent probe 1-aminoanthracene, which was efficiently displaced by the steroidal sex pheromone, as well as by several odorants.

scholarly journals A Pre-Vaccination Baseline of SARS-CoV-2 Genetic Surveillance and Diversity in the United States

Viruses ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 104
Author(s):  
Adam A. Capoferri ◽  
Wei Shao ◽  
Jon Spindler ◽  
John M. Coffin ◽  
Jason W. Rausch ◽  
...  
Keyword(s):  
United States ◽  
Genetic Diversity ◽  
Rna Virus ◽  
Viral Evolution ◽  
The United States ◽  
Virus Spread ◽  
Immune Pressure ◽  
Viral Genetic Diversity ◽  
Genetic Sampling ◽  
The U.S

COVID-19 vaccines were first administered on 15 December 2020, marking an important transition point for the spread of SARS-CoV-2 in the United States (U.S.). Prior to this point in time, the virus spread to an almost completely immunologically naïve population, whereas subsequently, vaccine-induced immune pressure and prior infections might be expected to influence viral evolution. Accordingly, we conducted a study to characterize the spread of SARS-CoV-2 in the U.S. pre-vaccination, investigate the depth and uniformity of genetic surveillance during this period, and measure and otherwise characterize changing viral genetic diversity, including by comparison with more recently emergent variants of concern (VOCs). In 2020, SARS-CoV-2 spread across the U.S. in three phases distinguishable by peaks in the numbers of infections and shifting geographical distributions. Virus was genetically sampled during this period at an overall rate of ~1.2%, though there was a substantial mismatch between case rates and genetic sampling nationwide. Viral genetic diversity tripled over this period but remained low in comparison to other widespread RNA virus pathogens, and although 54 amino acid changes were detected at frequencies exceeding 5%, linkage among them was not observed. Based on our collective observations, our analysis supports a targeted strategy for worldwide genetic surveillance as perhaps the most sensitive and efficient means of detecting new VOCs.

scholarly journals Antigenic variation among isolates of infectious salmon anaemia virus correlates with genetic variation of the viral haemagglutinin gene

2001 ◽  
Vol 82 (12) ◽  
pp. 2869-2879 ◽  
Author(s):  
Frederick S. B. Kibenge ◽  
Molly J. T. Kibenge ◽  
Patricia K. McKenna ◽  
Paul Stothard ◽  
Rebecca Marshall ◽  
...  
Keyword(s):  
Amino Acid ◽  
Sequence Analysis ◽  
Amino Acid Sequence ◽  
Antigenic Variation ◽  
Comparative Sequence Analysis ◽  
Infectious Salmon Anaemia Virus ◽  
Marine Aquaculture ◽  
Sequence Identity ◽  
Ha Gene ◽  
Infectious Salmon Anaemia

Infectious salmon anaemia virus (ISAV), an orthomyxovirus-like virus, is an important fish pathogen in marine aquaculture. Virus neutralization of 24 ISAV isolates in the TO cell line using rabbit antisera to the whole virus and comparative sequence analysis of their haemagglutinin (HA) genes have allowed elaboration on the variation of ISAV isolates. The 24 viruses were neutralized to varying degrees, revealing two major antigenic groups, one American and one European. Sequence analysis of the HA gene also revealed two groups of viruses (genotypes) that correlated with the antigenic groupings. The two HA subtypes had nucleotide sequence identity of only ⩽79·4% and amino acid sequence identity of ⩽84·5% whereas, within each subtype, the sequence identities were 90·7% or higher. This grouping was also evident upon phylogenetic analysis, which revealed two distinct phylogenetic families. Between the two groups, the amino acid sequence was most variable in the C-terminal region and included deletions of 4–16 amino acids in all isolates relative to ISAV isolate RPC/NB-980 280-2. In order to view the relationships among these sequences and the HA sequences of the established orthomyxoviruses, a second phylogenetic tree was constructed which showed the ISAV sequences to be more closely related to sequences from Influenzavirus A and Influenzavirus B than to sequences from Influenzavirus C and Thogotovirus. The extensive deletions in the gene of European ISAV isolates lead us to speculate that the archetypal ISAV was probably of Canadian origin.

scholarly journals Long-Term Evolution of the Hypervariable Region of Hepatitis C Virus in a Common-Source-Infected Cohort

1998 ◽  
Vol 72 (6) ◽  
pp. 4893-4905 ◽  
Author(s):  
Jane McAllister ◽  
Carmela Casino ◽  
Fiona Davidson ◽  
Joan Power ◽  
Emer Lawlor ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Amino Acid ◽  
Hypervariable Region ◽  
Long Term Evolution ◽  
Common Source ◽  
Single Individual ◽  
Term Evolution ◽  
Flanking Regions

ABSTRACT The long-term evolution of the hepatitis C virus hypervariable region (HVR) and flanking regions of the E1 and E2 envelope proteins have been studied in a cohort of women infected from a common source of anti-D immunoglobulin. Whereas virus sequences in the infectious source were relatively homogeneous, distinct HVR variants were observed in each anti-D recipient, indicating that this region can evolve in multiple directions from the same point. Where HVR variants with dissimilar sequences were present in a single individual, the frequency of synonymous substitution in the flanking regions suggested that the lineages diverged more than a decade previously. Even where a single major HVR variant was present in an infected individual, this lineage was usually several years old. Multiple lineages can therefore coexist during long periods of chronic infection without replacement. The characteristics of amino acid substitution in the HVR were not consistent with the random accumulation of mutations and imply that amino acid replacement in the HVR was strongly constrained. Another variable region of E2 centered on codon 60 shows similar constraints, while HVR2 was relatively unconstrained. Several of these features are difficult to explain if a neutralizing immune response against the HVR is the only selective force operating on E2. The impact of PCR artifacts such as nucleotide misincorporation and the shuffling of dissimilar templates is discussed.

scholarly journals Identification of a New Infectious Pancreatic Necrosis Virus (IPNV) Variant in Atlantic Salmon (Salmo salar L.) that can Cause High Mortality Even in Genetically Resistant Fish

2021 ◽  
Vol 12 ◽  
Author(s):  
Borghild Hillestad ◽  
Stein Johannessen ◽  
Geir Olav Melingen ◽  
Hooman K. Moghadam
Keyword(s):  
Amino Acid ◽  
Atlantic Salmon ◽  
Pancreatic Necrosis ◽  
Single Gene ◽  
Head Kidney ◽  
Comparative Sequence Analysis ◽  
Infectious Pancreatic Necrosis Virus ◽  
Life Cycles ◽  
New Variant ◽  
Infectious Pancreatic Necrosis

Infectious pancreatic necrosis (IPN) is an important viral disease of salmonids that can affect fish during various life cycles. In Atlantic salmon, selecting for genetically resistant fish against IPN has been one of the most highly praised success stories in the history of fish breeding. During the late 2000s, the findings that resistance against this disease has a significant genetic component, which is mainly controlled by variations in a single gene, have helped to reduce the IPN outbreaks to a great extent. In this paper, we present the identification of a new variant of the IPN virus from a field outbreak in Western Norway that had caused mortality, even in genetically resistant salmon. We recovered and assembled the full-length genome of this virus, following the deep-sequencing of the head-kidney transcriptome. The comparative sequence analysis revealed that for the critical amino acid motifs, previously found to be associated with the degree of virulence, the newly identified variant is similar to the virus’s avirulent form. However, we detected a set of deduced amino acid residues, particularly in the hypervariable domain of the VP2, that collectively are unique to this variant compared to all other reference sequences assessed in this study. We suggest that these mutations have likely equipped the virus with the capacity to escape the host defence mechanism more efficiently, even in the genetically deemed IPN resistant fish.

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