Whole genome sequencing, variant analysis, phylogenetics, and deep sequencing of Zika virus strains

Shrivastava, Susmita; Puri, Vinita; Dilley, Kari A.; Ngouajio, Erica; Shifflett, Jessica; Oldfield, Lauren M.; Fedorova, Nadia; Hu, Lihui; Williams, Torrey; Durbin, Alan; Amedeo, Paolo; Rashid, Sujatha; Shabman, Reed S.; Pickett, Brett E.

doi:10.1038/s41598-018-34147-7

Cited by 24 publications

(19 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The nature of the mutation is also similar, resulting in just a small increase in the amino acid side chain. The amino acid polymorphism identified in ZV BR 2015/15098 NS2A 117 presents the same character as minor variants previously identified at this same position through next-generation sequencing 22 . There are five other isolates (KX520666/BR/2015, KY648934/MX/2016, KX446951/MX/2016, MH900227/MX/2016 and KX377336/MY/1966) in our datasets that contain this same substitution (A117V).…”

Section: Discussionsupporting

confidence: 79%

Genetic and biological characterisation of Zika virus isolates from different Brazilian regions

Strottmann

Zanluca

Mosimann

et al. 2019

Mem. Inst. Oswaldo Cruz

View full text Add to dashboard Cite

BACKGROUND Zika virus (ZIKV) infections reported in recent epidemics have been linked to clinical complications that had never been associated with ZIKV before. Adaptive mutations could have contributed to the successful emergence of ZIKV as a global health threat to a nonimmune population. However, the causal relationships between the ZIKV genetic determinants, the pathogenesis and the rapid spread in Latin America and in the Caribbean remain widely unknown. OBJECTIVES The aim of this study was to characterise three ZIKV isolates obtained from patient samples during the 2015/2016 Brazilian epidemics. METHODS The ZIKV genomes of these strains were completely sequenced and in vitro infection kinetics experiments were carried out in cell lines and human primary cells. FINDINGS Eight nonsynonymous substitutions throughout the viral genome of the three Brazilian isolates were identified. Infection kinetics experiments were carried out with mammalian cell lines A549, Huh7.5, Vero E6 and human monocyte-derived dendritic cells (mdDCs) and insect cells (Aag2, C6/36 and AP61) and suggest that some of these mutations might be associated with distinct viral fitness. The clinical isolates also presented differences in their infectivity rates when compared to the well-established ZIKV strains (MR766 and PE243), especially in their abilities to infect mammalian cells. MAIN CONCLUSIONS Genomic analysis of three recent ZIKV isolates revealed some nonsynonymous substitutions, which could have an impact on the viral fitness in mammalian and insect cells.

show abstract

Section: Discussionsupporting

confidence: 79%

Genetic and biological characterisation of Zika virus isolates from different Brazilian regions

Strottmann

Zanluca

Mosimann

et al. 2019

Mem. Inst. Oswaldo Cruz

View full text Add to dashboard Cite

show abstract

“…In vivo, the virus derived from WT-ZIKV-infected mouse tissues incurred a NS2A A117V substitution. This substitution was previously detected as a minor variant in wild-type ZIKV strains DakAr41524, PA259249, PA259634, and THA/PL-Cal_ZV/2013; and the opposite substitution of V117A was a minor variant in ZIKV strains MEX-I-44/2016 and MYS-P6-740 [23,28]. This implies that both amino acids, alanine and valine, are present at NS2A 117 in varying frequencies, and infection of AG129 mice may select for valine.…”

Section: Discussionmentioning

confidence: 91%

Attenuation of Zika Virus by Passage in Human HeLa Cells

Collins

Widen

et al. 2019

Vaccines

View full text Add to dashboard Cite

Zika virus (ZIKV) is a mosquito-borne Flavivirus. Previous studies have shown that mosquito-transmitted flaviviruses, including yellow fever, Japanese encephalitis, and West Nile viruses, could be attenuated by serial passaging in human HeLa cells. Therefore, it was hypothesized that wild-type ZIKV would also be attenuated after HeLa cell passaging. A human isolate from the recent ZIKV epidemic was subjected to serial HeLa cell passaging, resulting in attenuated in vitro replication in both Vero and A549 cells. Additionally, infection of AG129 mice with 10 plaque forming units (pfu) of wild-type ZIKV led to viremia and mortality at 12 days, whereas infection with 103 pfu of HeLa-passage 6 (P6) ZIKV led to lower viremia, significant delay in mortality (median survival: 23 days), and increased cytokine and chemokine responses. Genomic sequencing of HeLa-passaged virus identified two amino acid substitutions as early as HeLa-P3: pre-membrane E87K and nonstructural protein 1 R103K. Furthermore, both substitutions were present in virus harvested from HeLa-P6-infected animal tissue. Together, these data show that, similarly to other mosquito-borne flaviviruses, ZIKV is attenuated following passaging in HeLa cells. This strategy can be used to improve understanding of substitutions that contribute to attenuation of ZIKV and be applied to vaccine development across multiple platforms.

show abstract

“…Undoubtedly, detection of novel virus variants and species has been facilitated by the dramatic progress in whole-genome sequencing [46][47][48][49][50][51], thanks to the advent of a number of next-generation sequencing methods allowing full-length sequencing at a fraction of the time and cost required for traditional Sanger sequencing [52].…”

Section: Sequence Of Target Rna Virusesmentioning

confidence: 99%

Targeting the RdRp of Emerging RNA Viruses: The Structure-Based Drug Design Challenge

et al. 2020

View full text Add to dashboard Cite

The RNA-dependent RNA polymerase (RdRp) is an essential enzyme for the viral replication process, catalyzing the viral RNA synthesis using a metal ion-dependent mechanism. In recent years, RdRp has emerged as an optimal target for the development of antiviral drugs, as demonstrated by recent approvals of sofosbuvir and remdesivir against Hepatitis C virus (HCV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), respectively. In this work, we overview the main sequence and structural features of the RdRp of emerging RNA viruses such as Coronaviruses, Flaviviruses, and HCV, as well as inhibition strategies implemented so far. While analyzing the structural information available on the RdRp of emerging RNA viruses, we provide examples of success stories such as for HCV and SARS-CoV-2. In contrast, Flaviviruses’ story has raised attention about how the lack of structural details on catalytically-competent or ligand-bound RdRp strongly hampers the application of structure-based drug design, either in repurposing and conventional approaches.

show abstract

Whole genome sequencing, variant analysis, phylogenetics, and deep sequencing of Zika virus strains

Cited by 24 publications

References 35 publications

Genetic and biological characterisation of Zika virus isolates from different Brazilian regions

Genetic and biological characterisation of Zika virus isolates from different Brazilian regions

Attenuation of Zika Virus by Passage in Human HeLa Cells

Targeting the RdRp of Emerging RNA Viruses: The Structure-Based Drug Design Challenge

Contact Info

Product

Resources

About