Sequence variability of HCV 3a isolates based on core gene in patients from Lahore, Pakistan

2019 ◽  
Vol 14 (10) ◽  
pp. 641-653
Author(s):  
Muhammad Ajmal Khan ◽  
Sumera Afzal Khan ◽  
Muhammad Hamayun ◽  
Muhammad Ali ◽  
Muhammad Idrees

Aim: To investigate the HCV 3a core sequence variation and amino acid substitutions of patients from Lahore, Pakistan. Materials & methods: Blood samples from HCV positive patients (n = 232) were collected for viral genotypes. Moreover, the nucleotide sequencing was performed for core gene of 20 samples. Results: Viral genotyping showed that 69.82% (n = 162) belonged to 3a genotype, 9.05% (1a; n = 21), 2.15% (3b; n = 5) and 18.98% were untypable (n = 44). Phylogenetic analyses suggest majority of our isolates clustered with previously reported reference isolates from Pakistan. The remaining isolates clustered with HCV-core sequences reported from Vietnam, Japan, Thailand, Iran, USA, Bangladesh, Malaysia and Morocco. Conclusion: We report HCV-core substitutions (G60E, R70Q, C91A, A94Q and Q63E/D) that could be associated with treatment response in Pakistani patients.

Genetics ◽  
2001 ◽  
Vol 158 (1) ◽  
pp. 279-290 ◽  
Author(s):  
Jorge Vieira ◽  
Bryant F McAllister ◽  
Brian Charlesworth

Abstract We analyze genetic variation at fused1, a locus that is close to the centromere of the X chromosome-autosome (X/4) fusion in Drosophila americana. In contrast to other X-linked and autosomal genes, for which a lack of population subdivision in D. americana has been observed at the DNA level, we find strong haplotype structure associated with the alternative chromosomal arrangements. There are several derived fixed differences at fused1 (including one amino acid replacement) between two haplotype classes of this locus. From these results, we obtain an estimate of an age of ∼0.61 million years for the origin of the two haplotypes of the fused1 gene. Haplotypes associated with the X/4 fusion have less DNA sequence variation at fused1 than haplotypes associated with the ancestral chromosome arrangement. The X/4 haplotypes also exhibit clinal variation for the allele frequencies of the three most common amino acid replacement polymorphisms, but not for adjacent silent polymorphisms. These patterns of variation are best explained as a result of selection acting on amino acid substitutions, with geographic variation in selection pressures.


1972 ◽  
Vol 130 (2) ◽  
pp. 539-546 ◽  
Author(s):  
Jean-Claude Jaton ◽  
D. G. Braun

The sequence of the N-terminal 69 residues of heavy chain from a homogeneous rabbit antibody to type III pneumococcal polysaccharide was determined. The sequence is similar to that found in heavy chains of normal pooled rabbit immunoglobulins of the same allotype Aa1. Two regions of the homogeneous heavy chain (residues 35–46 and 62–69) are very similar to corresponding regions of heavy chains from rabbit Aa2 immunoglobulin, as well as from mouse, guinea-pig and human immunoglobulins. In contrast, residues 47–62 appear to be variable. Comparison in this section with another homogeneous anti-pneumococcal antibody (Strosberg et al., 1972) of related specificity and of the same allotype indicates sequence variation in at least three positions. An antibody to group C streptococcal carbohydrate of allotype Aa2 (Fleischman, 1971) differs by five amino acids in the same region of the heavy chain. Sequence variability between these three antibodies does not occur in homologous positions within this variable section. Allotype-related sequences could not be identified in section 34–65.


mBio ◽  
2016 ◽  
Vol 7 (5) ◽  
Author(s):  
John H.-O. Pettersson ◽  
Vegard Eldholm ◽  
Stephen J. Seligman ◽  
Åke Lundkvist ◽  
Andrew K. Falconar ◽  
...  

ABSTRACT The unexpected emergence of Zika virus (ZIKV) in the Pacific Islands and Latin America and its association with congenital Zika virus syndrome (CZVS) (which includes microcephaly) and Guillain-Barré syndrome (GBS) have stimulated wide-ranging research. High densities of susceptible Aedes spp., immunologically naive human populations, global population growth with increased urbanization, and escalation of global transportation of humans and commercial goods carrying vectors and ZIKV undoubtedly enhanced the emergence of ZIKV. However, flavivirus mutations accumulate with time, increasing the likelihood that genetic viral differences are determinants of change in viral phenotype. Based on comparative ZIKV complete genome phylogenetic analyses and temporal estimates, we identify amino acid substitutions that may be associated with increased viral epidemicity, CZVS, and GBS. Reverse genetics, vector competence, and seroepidemiological studies will test our hypothesis that these amino acid substitutions are determinants of epidemic and neurotropic ZIKV emergence.


1998 ◽  
Vol 42 (8) ◽  
pp. 1980-1984 ◽  
Author(s):  
Patricia A. Bradford ◽  
Youjun Yang ◽  
Daniel Sahm ◽  
Ilze Grope ◽  
Dace Gardovska ◽  
...  

ABSTRACT At a children’s hospital in Riga, Latvia, isolates identified asSalmonella typhimurium were found to be resistant to expanded-spectrum cephalosporins. Two of the resistant strains were analyzed for the mechanism of cephalosporin resistance. Isoelectric focusing revealed a common β-lactamase with a pI of 8.8. In addition, one of the strains produced a pI 7.6 β-lactamase. A transconjugant producing only the pI 7.6 enzyme was susceptible to expanded-spectrum cephalosporins; therefore, this enzyme was most likely SHV-1. Transformants producing only the pI 8.8 β-lactamase were resistant to cefotaxime and aztreonam but were susceptible or intermediate to ceftazidime. A substrate profile determined spectrophotometrically with purified enzyme revealed potent activity against cefotaxime, with a relative k cat value of 95 (benzylpenicillin equal to 100). The enzyme showed lower relativek cat values for ceftazidime (3.3) and aztreonam (9.3). In addition, the enzyme was inhibited by clavulanate, sulbactam and tazobactam, with 50% inhibitory concentrations of 19, 100, and 3.4 nM, respectively. These results indicated the presence of an unusual extended-spectrum β-lactamase. The gene expressing the pI 8.8 β-lactamase was cloned. Nucleotide sequencing revealed a β-lactamase gene that differs from the gene encoding CTX-M-2, which also originated from S. typhimurium, by 11 nucleotides, 4 of which result in amino acid substitutions: Ala27Thr, Val230Gly, Glu254Ala, and Ile278Val. These results indicated the presence of a novel extended-spectrum β-lactamase, designated CTX-M-5, that specifically confers resistance to cefotaxime.


2020 ◽  
Author(s):  
Kazutaka Katoh ◽  
Naoyuki Iwabe ◽  
Takashi Miyata

AbstractDNA polymerase δ (polδ) is one of the major DNA polymerases that replicate chromosomal genomes in eukaryotes. Given the essential role of this protein, its phylogenetic tree was expected to reflect the relationship between taxa, like many other essential proteins. However, the tree of the catalytic subunit of polδ showed an unexpectedly strong heterogeneity among vertebrate lineages in evolutionary rate at the amino acid level, suggesting unusual amino acid substitutions specifically in the ancestral mammalian lineage. Structural and phylogenetic analyses were used to pinpoint where and when these amino acid substitutions occurred: around the 3′-5′ exonuclease domain in later mammal ancestry, after the split between monotremes and therians. The 3′-5′ exonuclease domain of this protein is known to have an impact on the fidelity of replication. Based on these observations, we explored the possibility that the amino acid substitutions we identified in polδ affected the mutation rate of entire chromosomal genomes in this time period.


2021 ◽  
Vol 8 ◽  
Author(s):  
Naveen Kumar ◽  
Richa Sood ◽  
Atul K. Pateriya ◽  
E. Venkatesakumar ◽  
R. Ramprabhu ◽  
...  

Ovine herpesvirus 2 (OvHV-2) is the causative agent of sheep-associated malignant catarrhal fever (SA-MCF), a highly fatal disease syndrome that predominantly affects susceptible hosts of the order Artiodactyla. In this study, an in-depth clinico-molecular investigation of SA-MCF disease in a morbid 50-days-old cattle calf (Bos taurus indicus) and asymptomatic infection in the in-contact reservoir hosts, sheep (Ovis aries), and goat (Capra hircus) housed on a farm located in the Southern India is reported. An OIE recommended SA-MCF type-specific PCR confirmed the etiological agent as OvHV-2. The genetic characterization and phylogenetic analyses based on the glycoprotein B (gB) gene indicate that three genetic variants of OvHV-2 had infected the animal cluster of this study. As the OvHV-2 infection eventually lead to the death of the cattle calf, and the fact that its gB sequence carried four unique amino acid substitutions (N169S, L594P, I645V, and V730A), an investigation of these substitutions impact on its stability and molecular flexibility was carried out. The mapping of these amino acid substitutions on the three-dimensional structure of gB coupled with supplementary investigations showed that these substitutions conveyed the molecular flexibility to the gB, at the cost of its stability. Future studies would be to investigate whether these gB substitutions have any impact on membrane fusion activity using a virus-free cell-to-cell membrane fusion assay. The study also highlights the importance of adopting stringent biosecurity measures where mixed animal farming is a common practice.


Genetics ◽  
1995 ◽  
Vol 141 (1) ◽  
pp. 237-244
Author(s):  
N Inomata ◽  
H Shibata ◽  
E Okuyama ◽  
T Yamazaki

Abstract To infer the genealogical relationships of alpha-amylase electromorphs of Drosophila melanogaster, we determined the nucleotide sequences of a collection of electromorphs sampled throughout the world. On average there were 1.0 amino acid substitutions between identical electromorphs and 3.9 between different electromorphs, respectively. We found that the evolution of AMY1 through AMY6 electromorphs occurred by sequential accumulation of single amino acid substitutions each causing one charge difference. The nucleotide diversities at synonymous sites within Amy1,Amy2,Amy3,Amy4 and Amy6 were 0.0321, 0.0000, 0.0355, 0.0059 and 0.0030, respectively. We also obtained evidence of genetic exchanges, such as intrachromosomal recombination, interchromosomal recombination or gene conversion, between the two duplicated Amy genes as well as among the alleles.


2008 ◽  
Vol 56 (2) ◽  
pp. 255-264 ◽  
Author(s):  
Olga Zorman Rojs ◽  
Uroš Krapež ◽  
Brigita Slavec ◽  
Sara Mankoč ◽  
Rahela Jurišič-Cizerl ◽  
...  

In 2004 and then in 2006 several outbreaks of infectious bursal disease (IBD) were reported in broiler and broiler breeder flocks in Slovenia. In this report ten recently emerged IBD viruses (IBDV) were characterised by sequence analysis of the VP2 hypervariable region and compared to previous Slovene IBDV strains from 1995/1996 and to some representative serotype 1 IBDV strains of different pathotypes. On the basis of nucleotide and amino acid identities, phylogenetic analyses and the presence of very virulent IBDV (vvIBDV) conserved amino acid substitutions, all Slovene isolates from recent outbreaks were identified as vvIBDV. Although some unique nucleotide exchanges and amino acid substitutions have been observed, the results of this study indicated that recent vvIBDV isolates are closely related with those from outbreaks in the 1990s. However, acute IBD has not been reported in commercial flocks in Slovenia for some years. This could lead to the conclusion that poor biosecurity and relaxed vaccination could be responsible for the re-emergence of vvIBDV.


2019 ◽  
Author(s):  
Krishna Unadkat ◽  
Justen B. Whittall

AbstractThere is a molecular basis for many sleep patterns and disorders involving circadian clock genes. In humans, “short-sleeper” behavior has been linked to specific amino acid substitutions in BHLHE41 (DEC2), yet little is known about variation at these sites and across this gene in mammals. We compare BHLHE41 coding sequences for 27 mammals. The coding sequence alignment length was 1794bp, of which 55.0% of base pairs were invariant among the sampled mammals. The mean pairwise nucleotide identity was 92.2%. Of the 598 residue amino acid alignment for mammals, 71.7% of amino acids were identical. The pairwise percent identity for amino acids was 94.8%. No other mammals had the same “short-sleeper” amino acid substitutions previously described from humans. Phylogenetic analyses based on the nucleotides of the coding sequence alignment are consistent with established mammalian relationships. Significant purifying selection was detected in 66.2% of variable codons. No codons exhibited significant signs of positive selection. Unexpectedly, the gorilla BHLHE41 sequence has a 318 bp insertion at the 5’ end of the coding sequence and a deletion of 195 bp near the 3’ end of the coding sequence (including the two short sleeper variable sites). Given the strong signal of purifying selection across this gene, phylogenetic congruence with expected relationships and generally conserved function among mammals investigated thus far, we suggest the unexpected indels predicted in the gorilla BHLHE41 may represent an annotation error and warrant experimental validation.


Author(s):  
Paola Cristina Resende ◽  
Edson Delatorre ◽  
Tiago Gräf ◽  
Daiana Mir ◽  
Fernando do Couto Motta ◽  
...  

AbstractDespite all efforts to control the COVID-19 spread, the SARS-CoV-2 reached South America within three months after its first detection in China, and Brazil became one of the hotspots of COVID-19 in the world. Several SARS-CoV-2 lineages have been identified and some local clusters have been described in this early pandemic phase in Western countries. Here we investigated the genetic diversity of SARS-CoV-2 during the early phase (late February to late April) of the epidemic in Brazil. Phylogenetic analyses revealed multiple introductions of SARS-CoV-2 in Brazil and the community transmission of a major B.1.1 lineage defined by two amino acid substitutions in the Nucleocapsid and ORF6. This SARS-CoV-2 Brazilian lineage was probably established during February 2020 and rapidly spread through the country, reaching different Brazilian regions by the middle of March 2020. Our study also supports occasional exportations of this Brazilian B.1.1 lineage to neighboring South American countries and to more distant countries before the implementation of international air travels restrictions in Brazil.


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