Host influence in the genomic composition of flaviviruses: A multivariate approach

Simón, Diego; Fajardo, Álvaro; Sóñora, Martín; Delfraro, Adriana; Musto, Héctor

doi:10.1016/j.bbrc.2017.06.088

Cited by 19 publications

(21 citation statements)

References 34 publications

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“…Codon usage is among the determinant factors that influence gene expression levels (Chaney and Clark 2015;Zhou et al 2016). Because viruses do not have tRNAs, and rely on host cell machinery for replication, co-evolution between a certain RNA virus and its susceptible hosts at codon usages have been observed (Franzo et al 2017;Rahman et al 2017;Simón et al 2017). However, ambiguity remains in the co-evolution patterns of different viruses.…”

Section: Discussionmentioning

confidence: 99%

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The adaptation of codon usage of +ssRNA viruses to their hosts

Tian

Shen

Murphy

et al. 2018

Infection, Genetics and Evolution

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Viruses depend on their host's cellular structure to survive. Most of them do not have tRNAs, their translation relies on hosts' tRNA pools. Over the course of evolution, viruses needed to optimally exploit cellular processes of their host. Thus, codon usage of a virus should coevolve with its host to efficiently and rapidly replicate. Some viruses can invade a broad spectrum of hosts (BSTVs), while others can invade a narrow spectrum only (NSTVs). Consequently, we test the hypothesis that similarity of codon usage preference and the degree of matching between BSTVs and their hosts will be lower than that of NSTVs, which only need to coevolve with few hosts. We compare the patterns of codon usage in 255 virus genomes to test this hypothesis. Our results show that NSTVs have a higher degree of matching to their hosts' tRNA pools than BSTVs. Further, analysis of the effective number of codons (ENC) infers that codon usage bias of NSTVs is relatively stronger than that of BSTVs. Thus, codon usage of NSTVs tends to better match their host than that of BSTVs. This supports the hypothesis that viruses adapt to the expression system of their host(s).

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Section: Discussionmentioning

confidence: 99%

“…Efficient replication seemingly requires that a virus and host have similar codon usage patterns to share a tRNA pool. Co-evolution between a certain RNA virus and its susceptible hosts at codon usages have been observed in many viruses (Franzo et al 2017;Rahman et al 2017;Simón et al 2017).…”

Section: Introductionmentioning

confidence: 99%

The adaptation of codon usage of +ssRNA viruses to their hosts

Tian

Shen

Murphy

et al. 2018

Infection, Genetics and Evolution

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“…Previous analysis [24] showed that the host environment differently affects the nucleotide, codon and dinucleotide composition in viruses of the Flaviviridae family. In particular, APOIV and other flaviviruses with no known insect vector show an under-representation of CpG, possibly a result of the ZAP-related vertebrate immune response targeting CpG-rich viruses.…”

Section: Resultsmentioning

confidence: 99%

“…To test the uses of the SDU we have collected polyprotein coding sequences of vertebrate- and invertebrate-specific viruses of the Flaviviridae family, analysed in previous research [24]. Our analysis focuses on two representatives of the dataset: the insect-specific Aedes flavivirus (AEFV, Genbank accession: AB488408.1) that usually affects Aedes spp.…”

Section: Methodsmentioning

confidence: 99%

Synonymous Dinucleotide Usage: A Codon-Aware Metric for Quantifying Dinucleotide Representation in Viruses

Lytras

Hughes

2020

Preprint

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9Distinct patterns of dinucleotide representation, such as CpG and UpA suppression, are characteristic 10 of certain viral genomes. Recent research has uncovered vertebrate immune mechanisms that select 11 against specific dinucleotides in targeted viruses. This evidence highlights the importance of 12 systematically examining the dinucleotide composition of viral genomes. We have developed a novel 13 metric, called Synonymous Dinucleotide Usage (SDU), for quantifying dinucleotide representation in 14 coding sequences. Our method compares the abundance of a given dinucleotide to the null 15 hypothesis of equal synonymous codon usage in the sequence. We present a Python3 package, 16DinuQ, for calculating SDU and other relevant metrics. We have applied this method on two sets of 17 invertebrate-and vertebrate-specific flaviviruses and rhabdoviruses. The SDU shows that the 18 vertebrate viruses exhibit consistently greater under-representation of CpG dinucleotides in all three 19 codon positions in both datasets. In comparison to existing metrics for dinucleotide quantification, the 20 SDU allows for a biologically informed interpretation of its values by comparing representation to an 21 expectation based on the codon table. Here we apply the method to viruses, but coding sequences 22 of other living organisms can be analysed in the same way. 23 24 Introduction 25 Certain dinucleotides, two nucleotides adjacent in a sequence, are known to be over-or under-26 represented in the genomes of living organisms, creating distinct compositional patterns [1]. 27Organisms with methylated genomes such as vertebrates and plants have low levels of CpG 28 dinucleotides. This is not the case for methylase-absent organisms like invertebrates, bacteria and 29 fungi [2,3]. The cause of CpG suppression lies in the DNA methylation mechanisms of vertebrates 30 and plants, where cytosine is frequently converted to thymine by DNA methyltransferases [4,5]. UpA 31 deprivation is consistently present in most living organisms, including prokaryotes. This bias is 32 suspected to be due to UpA-rich mRNA being unstable and more prone to degradation by cytoplasmic 33 RNAses [6,7].34 Similar patterns of dinucleotide composition have been observed in RNA and DNA viruses, and 35 appear to have a functional role in the infection and propagation of the viruses [8]. Studies have 36 shown that experimentally increasing UpA and CpG levels in RNA viruses leads to a decrease in 37 replication and subsequent viral attenuation, while decreasing their abundance has the opposite 38 effect [9-11]. Influenza CpG-/UpA-rich sequences have also been shown to have reduced replication 39 in vivo, causing a more powerful immune response, and in the case of CpG increase, showing 40 reduced clinical severity [12]. A similar decrease in replication and virulence has been observed in 41 CpG-/UpA-increased yellow fever virus [13]. 42Recently, a host immune mechanism of vertebrates which acts on viral genomes on the dinucleotide 43 level, has been uncovered. The Zinc-finge...

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“…Zika virus (ZIKV) is a positive-sense single-stranded RNA virus that is a member of the genus Flavivirus [5]. Currently, the genus Flavivirus consists of fifty-three documented species along with a growing number of tentative species [6]. These viruses produce a single polyprotein that is processed to produce three structural proteins (C, prM, and E) and seven nonstructural proteins [5].…”

Section: Introductionmentioning

confidence: 99%

Codelivery of improved immune complex and virus-like particle vaccines containing Zika virus envelope domain III synergistically enhances immunogenicity

Diamos

Pardhe

Sun

et al. 2020

Vaccine

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a b s t r a c tZika virus (ZIKV) reemergence poses a significant health threat especially due to its risks to fetal development, necessitating safe and effective vaccines that can protect pregnant women. Zika envelope domain III (ZE3) has been identified as a safe and effective vaccine candidate, however it is poorly immunogenic. We previously showed that plant-made recombinant immune complex (RIC) vaccines are a robust platform to improve the immunogenicity of weak antigens. In this study, we altered the antigen fusion site on the RIC platform to accommodate N-terminal fusion to the IgG heavy chain (N-RIC), and thus a wider range of antigens, with a resulting 40% improvement in RIC expression over the normal C-terminal fusion (C-RIC). Both types of RICs containing ZE3 were efficiently assembled in plants and purified to >95% homogeneity with a simple one-step purification. Both ZE3 RICs strongly bound complement receptor C1q and elicited strong ZE3-specific antibody titers that correlated with ZIKV neutralization. When either N-RIC or C-RIC was codelivered with plant-produced hepatitis B core (HBc) virus-like particles (VLP) displaying ZE3, the combination elicited 5-fold greater antibody titers (>1,000,000) and more strongly neutralized ZIKV than either RICs or VLPs alone, after only two doses without adjuvant. These findings demonstrate that antigens that require a free N-terminus for optimal antigen display can now be used with the RIC system, and that plant-made RICs and VLPs are highly effective vaccines targeting ZE3. Thus, the RIC platform can be more generally applied to a wider variety of antigens.

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Host influence in the genomic composition of flaviviruses: A multivariate approach

Cited by 19 publications

References 34 publications

The adaptation of codon usage of +ssRNA viruses to their hosts

The adaptation of codon usage of +ssRNA viruses to their hosts

Synonymous Dinucleotide Usage: A Codon-Aware Metric for Quantifying Dinucleotide Representation in Viruses

Codelivery of improved immune complex and virus-like particle vaccines containing Zika virus envelope domain III synergistically enhances immunogenicity

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