scholarly journals Within-Host Variations of Human Papillomavirus Reveal APOBEC Signature Mutagenesis in the Viral Genome

2018 ◽  
Vol 92 (12) ◽  
pp. e00017-18 ◽  
Author(s):  
Yusuke Hirose ◽  
Mamiko Onuki ◽  
Yuri Tenjimbayashi ◽  
Seiichiro Mori ◽  
Yoshiyuki Ishii ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Cervical Cancer ◽  
Deep Sequencing ◽  
Viral Genome ◽  
Reference Sequence ◽  
Characteristic Change ◽  
Whole Genome ◽  
Cervical Carcinogenesis ◽  
Genome Sequences ◽  
Host Genetic

ABSTRACTPersistent infection with oncogenic human papillomaviruses (HPVs) causes cervical cancer, accompanied by the accumulation of somatic mutations into the host genome. There are concomitant genetic changes in the HPV genome during viral infection; however, their relevance to cervical carcinogenesis is poorly understood. Here, we explored within-host genetic diversity of HPV by performing deep-sequencing analyses of viral whole-genome sequences in clinical specimens. The whole genomes of HPV types 16, 52, and 58 were amplified by type-specific PCR from total cellular DNA of cervical exfoliated cells collected from patients with cervical intraepithelial neoplasia (CIN) and invasive cervical cancer (ICC) and were deep sequenced. After constructing a reference viral genome sequence for each specimen, nucleotide positions showing changes with >0.5% frequencies compared to the reference sequence were determined for individual samples. In total, 1,052 positions of nucleotide variations were detected in HPV genomes from 151 samples (CIN1,n= 56; CIN2/3,n= 68; ICC,n= 27), with various numbers per sample. Overall, C-to-T and C-to-A substitutions were the dominant changes observed across all histological grades. While C-to-T transitions were predominantly detected in CIN1, their prevalence was decreased in CIN2/3 and fell below that of C-to-A transversions in ICC. Analysis of the trinucleotide context encompassing substituted bases revealed that TpCpN, a preferred target sequence for cellular APOBEC cytosine deaminases, was a primary site for C-to-T substitutions in the HPV genome. These results strongly imply that the APOBEC proteins are drivers of HPV genome mutation, particularly in CIN1 lesions.IMPORTANCEHPVs exhibit surprisingly high levels of genetic diversity, including a large repertoire of minor genomic variants in each viral genotype. Here, by conducting deep-sequencing analyses, we show for the first time a comprehensive snapshot of the within-host genetic diversity of high-risk HPVs during cervical carcinogenesis. Quasispecies harboring minor nucleotide variations in viral whole-genome sequences were extensively observed across different grades of CIN and cervical cancer. Among the within-host variations, C-to-T transitions, a characteristic change mediated by cellular APOBEC cytosine deaminases, were predominantly detected throughout the whole viral genome, most strikingly in low-grade CIN lesions. The results strongly suggest that within-host variations of the HPV genome are primarily generated through the interaction with host cell DNA-editing enzymes and that such within-host variability is an evolutionary source of the genetic diversity of HPVs.

scholarly journals Direct whole-genome deep-sequencing of human respiratory syncytial virus A and B from Vietnamese children identifies distinct patterns of inter- and intra-host evolution

2015 ◽  
Vol 96 (12) ◽  
pp. 3470-3483 ◽  
Author(s):  
Lien Anh Ha Do ◽  
Andreas Wilm ◽  
H. Rogier van Doorn ◽  
Ha Minh Lam ◽  
Shuzhen Sim ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Respiratory Syncytial Virus ◽  
Deep Sequencing ◽  
Human Respiratory Syncytial Virus ◽  
Whole Genome ◽  
M Gene ◽  
Upper Airways ◽  
Host Genetic ◽  
Syncytial Virus ◽  
Tract Infections

Human respiratory syncytial virus (RSV) is the major cause of lower respiratory tract infections in children < 2 years of age. Little is known about RSV intra-host genetic diversity over the course of infection or about the immune pressures that drive RSV molecular evolution. We performed whole-genome deep-sequencing on 53 RSV-positive samples (37 RSV subgroup A and 16 RSV subgroup B) collected from the upper airways of hospitalized children in southern Vietnam over two consecutive seasons. RSV A NA1 and RSV B BA9 were the predominant genotypes found in our samples, consistent with other reports on global RSV circulation during the same period. For both RSV A and B, the M gene was the most conserved, confirming its potential as a target for novel therapeutics. The G gene was the most variable and was the only gene under detectable positive selection. Further, positively selected sites in G were found in close proximity to and in some cases overlapped with predicted glycosylation motifs, suggesting that selection on amino acid glycosylation may drive viral genetic diversity. We further identified hotspots and coldspots of intra-host genetic diversity in the RSV genome, some of which may highlight previously unknown regions of functional importance.

scholarly journals Evolution and genetic diversity of SARSCoV-2 in Africa using whole genome sequences

2020 ◽  
Author(s):  
Babatunde Olarenwaju Motayo ◽  
Olukunle Oluwapamilerin Oluwasemowo ◽  
Babatunde Adebiyi Olusola ◽  
Paul Akiniyi Akinduti ◽  
Olamide T Arege ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Whole Genome ◽  
Genome Sequences

scholarly journals Whole-Genome Characterization and Genotyping of Global WU Polyomavirus Strains

2010 ◽  
Vol 84 (12) ◽  
pp. 6229-6234 ◽  
Author(s):  
Seweryn Bialasiewicz ◽  
Rebecca Rockett ◽  
David W. Whiley ◽  
Yacine Abed ◽  
Tobias Allander ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Discriminatory Power ◽  
Whole Genome ◽  
Nucleotide Variation ◽  
Genome Sequences ◽  
Typing Method ◽  
Genome Characterization ◽  
Wu Polyomavirus

ABSTRACT Exploration of the genetic diversity of WU polyomavirus (WUV) has been limited in terms of the specimen numbers and particularly the sizes of the genomic fragments analyzed. Using whole-genome sequencing of 48 WUV strains collected in four continents over a 5-year period and 16 publicly available whole-genome sequences, we identified three main WUV clades and five subtypes, provisionally termed Ia, Ib, Ic, II, IIIa, and IIIb. Overall nucleotide variation was low (0 to 1.2%). The discriminatory power of the previous VP2 fragment typing method was found to be limited, and a new, larger genotyping region within the VP2/1 interface was proposed.

scholarly journals Whole-Genome Sequencing and Variant Analysis of Human Papillomavirus 16 Infections

2017 ◽  
Vol 91 (19) ◽  
Author(s):  
Pascal van der Weele ◽  
Chris J. L. M. Meijer ◽  
Audrey J. King
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Cancer Progression ◽  
Viral Genome ◽  
Sequence Diversity ◽  
Whole Genome ◽  
Human Papillomavirus 16 ◽  
Persistent Infections ◽  
Hpv16 Infection

ABSTRACT Human papillomavirus (HPV) is a strongly conserved DNA virus, high-risk types of which can cause cervical cancer in persistent infections. The most common type found in HPV-attributable cancer is HPV16, which can be subdivided into four lineages (A to D) with different carcinogenic properties. Studies have shown HPV16 sequence diversity in different geographical areas, but only limited information is available regarding HPV16 diversity within a population, especially at the whole-genome level. We analyzed HPV16 major variant diversity and conservation in persistent infections and performed a single nucleotide polymorphism (SNP) comparison between persistent and clearing infections. Materials were obtained in the Netherlands from a cohort study with longitudinal follow-up for up to 3 years. Our analysis shows a remarkably large variant diversity in the population. Whole-genome sequences were obtained for 57 persistent and 59 clearing HPV16 infections, resulting in 109 unique variants. Interestingly, persistent infections were completely conserved through time. One reinfection event was identified where the initial and follow-up samples clustered differently. Non-A1/A2 variants seemed to clear preferentially (P = 0.02). Our analysis shows that population-wide HPV16 sequence diversity is very large. In persistent infections, the HPV16 sequence was fully conserved. Sequencing can identify HPV16 reinfections, although occurrence is rare. SNP comparison identified no strongly acting effect of the viral genome affecting HPV16 infection clearance or persistence in up to 3 years of follow-up. These findings suggest the progression of an early HPV16 infection could be host related. IMPORTANCE Human papillomavirus 16 (HPV16) is the predominant type found in cervical cancer. Progression of initial infection to cervical cancer has been linked to sequence properties; however, knowledge of variants circulating in European populations, especially with longitudinal follow-up, is limited. By sequencing a number of infections with known follow-up for up to 3 years, we gained initial insights into the genetic diversity of HPV16 and the effects of the viral genome on the persistence of infections. A SNP comparison between sequences obtained from clearing and persistent infections did not identify strongly acting DNA variations responsible for these infection outcomes. In addition, we identified an HPV16 reinfection event where sequencing of initial and follow-up samples showed different HPV16 variants. Based on conventional genotyping, this infection would incorrectly be considered a persistent HPV16 infection. In the context of vaccine efficacy and monitoring studies, such infections could potentially cause reduced reported efficacy or efficiency.

scholarly journals Evolution and Genetic Diversity of SARSCoV-2 in Africa Using Whole Genome Sequences

2020 ◽  
Author(s):  
Babatunde Olarenwaju Motayo ◽  
Olukunle Oluwapamilerin Oluwasemowo ◽  
Paul Akiniyi Akinduti ◽  
Babatunde Adebiyi Olusola ◽  
Olumide T Aerege ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Amino Acid ◽  
Spike Protein ◽  
Recent Common Ancestor ◽  
Whole Genome ◽  
Genome Sequences ◽  
Protein Amino Acid ◽  
Protein Variant ◽  
Health Crisis ◽  
Most Recent Common Ancestor

ABSTRACTThe ongoing SARSCoV-2 pandemic was introduced into Africa on 14th February 2020 and has rapidly spread across the continent causing severe public health crisis and mortality. We investigated the genetic diversity and evolution of this virus during the early outbreak months using whole genome sequences. We performed; recombination analysis against closely related CoV, Bayesian time scaled phylogeny and investigated spike protein amino acid mutations. Results from our analysis showed recombination signals between the AfrSARSCoV-2 sequences and reference sequences within the N and S genes. The evolutionary rate of the AfrSARSCoV-2 was 4.133 × 10−4 high posterior density HPD (4.132 × 10−4 to 4.134 × 10−4) substitutions/site/year. The time to most recent common ancestor TMRCA of the African strains was December 7th 2019. The AfrSARCoV-2 sequences diversified into two lineages A and B with B being more diverse with multiple sub-lineages confirmed by both maximum clade credibility MCC tree and PANGOLIN software. There was a high prevalence of the D614-G spike protein amino acid mutation (82.61%) among the African strains. Our study has revealed a rapidly diversifying viral population with the G614 spike protein variant dominating, we advocate for up scaling NGS sequencing platforms across Africa to enhance surveillance and aid control effort of SARSCoV-2 in Africa.

scholarly journals Clostridioides difficile Whole-Genome Sequencing Reveals Limited Within-Host Genetic Diversity in a Pediatric Cohort

2019 ◽  
Vol 57 (9) ◽  
Author(s):  
Aakash Balaji ◽  
Egon A. Ozer ◽  
Larry K. Kociolek
Keyword(s):  
Genetic Diversity ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Core Genome ◽  
Genetic Relatedness ◽  
The Other ◽  
Whole Genome ◽  
Content Type ◽  
Clostridioides Difficile ◽  
Host Genetic

ABSTRACT Whole-genome sequencing (WGS) is a highly sensitive method for identifying genetic relatedness and transmission of Clostridioides difficile strains. Previous studies suggest that as few as 3 core genome single-nucleotide variants (SNVs) discriminate between genetically distinct isolates. Because a single C. difficile colony is selected from culture for WGS, significant within-host genetic diversity could preclude identification of transmission events. To evaluate the likelihood of missed transmission events using WGS of single colonies from culture, we examined within-host genetic diversity among C. difficile isolates collected from children. We performed WGS using an Illumina MiSeq instrument on 8 C. difficile colonies randomly selected from each culture performed on stool collected from 10 children (8 children diagnosed with C. difficile infection and 2 children with asymptomatic carriage); 77/80 (96%) isolate sequences were successfully assembled. Among 8/10 (80%) children, all isolates were the same sequence type (ST). The other 2 children each had mixed infection with two STs, although one ST predominated. Among 9/10 (90%) children, isotypic isolates differed by ≤2 SNVs; an isotypic isolate in the remaining child differed by 3 to SNVs relative to the other isolates from that child. Overall, among the 77 isolates collected from 10 stool cultures, 74/77 (96%) were clonal (i.e., same ST and ≤2 core genome SNVs) to other isolates in stool culture. In summary, we identified rare C. difficile within-host genetic diversity in children, suggesting that WGS of a single colony from stool is likely to appropriately characterize isolate clonality and putative transmission events in the majority of cases.

scholarly journals Whole-Genome Assemblies for Three Yersinia pestis Strains Isolated in Erenhot, China

2020 ◽  
Vol 9 (45) ◽  
Author(s):  
Jing Wang ◽  
Xifeng Yang ◽  
Hongyuan Zheng ◽  
Li Tian ◽  
Qi Shi ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Yersinia Pestis ◽  
Draft Genome ◽  
Meriones Unguiculatus ◽  
Whole Genome ◽  
Genome Sequences ◽  
Content Type ◽  
Genome Assemblies

ABSTRACT To explore the genetic diversity of Yersinia pestis strains in Erenhot, China, and their relationship with Mongolian strains, we collected and sequenced three Y. pestis strains from Erenhot, China, in 2018. Here, we report the draft genome sequences of three Y. pestis bv. Medievalis strains belonging to the 2.MED phylogroup that were circulating in Meriones unguiculatus populations.

scholarly journals Human papillomavirus 16 sub-lineage dispersal and cervical cancer risk worldwide: Whole viral genome sequences from 7116 HPV16-positive women

2019 ◽  
Vol 7 ◽  
pp. 67-74 ◽  
Author(s):  
Gary M. Clifford ◽  
Vanessa Tenet ◽  
Damien Georges ◽  
Laia Alemany ◽  
Miquel Angel Pavón ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Cancer Risk ◽  
Viral Genome ◽  
Genome Sequences ◽  
Human Papillomavirus 16 ◽  
Cervical Cancer Risk

scholarly journals The Ever-Expanding Pseudomonas Genus: Description of 43 New Species and Partition of the Pseudomonas Putida Group

2021 ◽  
Author(s):  
Léa Girard ◽  
Cédric Lood ◽  
Monica Höfte ◽  
Peter Vandamme ◽  
Hassan Rokni-Zadeh ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Whole Genome ◽  
Genome Sequences ◽  
Taxonomic Assignment ◽  
Metabolic Potential ◽  
Rpod Gene ◽  
Integrative Studies ◽  
Pseudomonas Species ◽  
Type Strains ◽  
Selection Of

The genus Pseudomonas hosts an extensive genetic diversity and is one of the largest genera among Gram-negative bacteria. Type strains of Pseudomonas are well-known to represent only a small fraction of this diversity and the number of available Pseudomonas genome sequences is increasing rapidly. Consequently, new Pseudomonas species are regularly reported and the number of species within the genus is in constant evolution. In this study, whole genome se-quencing enabled us to define 43 new Pseudomonas species and to provide an update of the Pseu-domonas evolutionary and taxonomic relationships. Phylogenies based on the rpoD gene and whole genome sequences, including 316 and 313 type strains of Pseudomonas, respectively, re-vealed sixteen groups of Pseudomonas and justified the partitioning of the P. putida group into fifteen subgroups. Pairwise average nucleotide identities were calculated between type strains and a selection of 60 genomes of non-type strains of Pseudomonas. Forty-one strains were incor-rectly assigned at the species level and among those, 19 strains were shown to represent an addi-tional 13 new Pseudomonas species that remain to be formally classified. This work pinpoints the importance of correct taxonomic assignment and phylogenetic classification in order to perform integrative studies linking genetic diversity, lifestyle and metabolic potential of Pseudomonas spp.

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