<i>In Silico</i>Analysis of Dengue Virus Serotype 2 Mutations Detected at the Intrahost Level in Patients with Different Clinical Outcomes

Torres, María Celeste; Karl, Ana Luiza Martins; Silva, Matheus Müller Pereira da; Dardenne, Laurent E.; Filippis, Ana María Bispo de

doi:10.1128/spectrum.00256-21

Cited by 3 publications

(4 citation statements)

References 97 publications

(182 reference statements)

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“…How, DENV adapt in the different hosts is an important question and the answer perhaps lies in the gene mutations. Therefore, we used CprM region sequencing and estimated single-nucleotide variants in these virus strains of different serotypes [40; 41]. This allowed us to determine the mutations to the collective fitness of the viruses [39].…”

Section: Discussionmentioning

confidence: 99%

“…It is well known that; beneficial mutations generally map to intrinsically disordered domains of the virus which are clustered to a specific part in the genome [2; 49]. Several studies demonstrated that, the continuous influx of several mutations in the direction of virus adaptation [22; 40]. Further, it is important to note that, phenotypically redundant adaptive alleles together enhance the host-specific DENV adaptation [50].…”

Section: Discussionmentioning

confidence: 99%

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Assessment of genetic diversity patterns of different serotypes of dengue virus, prevalent in patients from Kerala, India: a strain specific mutation study and its relevance to pathogenesis

Niranjan

Sankari

Manoj

et al. 2023

Preprint

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The mutations are the key mechanisms responsible for virus survival and its fitness in the host. This process of mutation is implicated in the development of pathogenesis of the dengue viral disease. We report that, all the four serotypes were found to be circulating in Kerala sate of India. Serotypes 1 and 3 were the predominant type (33.3 %) compared to others. The prevalence of co-infection of serotype 1 and 4 was the highest percentage (11.1 %) compared to serotype 2 and serotype 3 (5.5 %). We further highlighted the immunopathological mechanisms of antibody neutralization, CD4+ T cell response and antibody dependent enhancements (ADE) for the possible cause of disease severity in coinfections. Serotype-1 does not show much variations from the previously reported strains from various regions of India. However, serotype-2 showed variations in the sequences from the other strains of serotype-2 previously reported from various regions of India and formed a distinct clade in the genotype-4. Serotype-3 and serotype-4 showed similarity with previously reported strains from India. Moreover, serotype-1 was grouping in genotype-5. Importantly, the serotype-2 grouped with genoptype-4 but exist separately. Serotype-3 was found to be grouped with the genotype-3. The serotype-4 show the very much similarities from the genotype-1 and shows little difference from the previously reported strains from India. Further, mutation in DENV-3 sequences, at position 235 (C to T) and 322 (G to T) shows an important phenomenon which might be adopted by the virus to survive. As severe dengue is linked with the serotype-2, the genetic variations in this serotype points towards the much specific strategy to be adopted in near future to manage the severe dengue disease. In conclusion, we can say that, genetic diversity in the CprM region is present in the different serotypes circulating in the patients from Kerala India and this information may help in the management of dengue viral disease.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Assessment of genetic diversity patterns of different serotypes of dengue virus, prevalent in patients from Kerala, India: a strain specific mutation study and its relevance to pathogenesis

Niranjan

Sankari

Manoj

et al. 2023

Preprint

View full text Add to dashboard Cite

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“…Due to the ability of DENV-2 to mutate and morph, this ability allows this serotype to bypass the human host's immune system in some cases, which poses a complication to the development of vaccines and therapeutics [37]. This ability of the DENV-2 to mutate and morph is also the reason why the only licensed tetravalent dengue vaccine, Dengvaxia ® (CYD-TDV), has shown lower efficacy against DENV-2 than the other serotypes [38].…”

Section: Discussionmentioning

confidence: 99%

In Silico Comparative Analysis of Predicted B Cell Epitopes against Dengue Virus (Serotypes 1–4) Isolated from the Philippines

et al. 2022

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Dengue is a viral mosquito-borne disease that rapidly spreads in tropical and subtropical countries, including the Philippines. One of its most distinguishing characteristics is the ability of the Dengue Virus (DENV) to easily surpass the innate responses of the body, thus activating B cells of the adaptive immunity to produce virus-specific antibodies. Moreover, Dengvaxia® is the only licensed vaccine for DENV, but recent studies showed that seronegative individuals become prone to increased disease severity and hospitalization. Owing to this limitation of the dengue vaccine, this study determined and compared consensus and unique B cell epitopes among each DENV (1–4) Philippine isolate to identify potential areas of interest for future vaccine studies and therapeutic developments. An in silico-based epitope prediction of forty (40) DENV 1–4 strains, each serotype represented by ten (10) sequences from The National Center for Biotechnology Information (NCBI), was conducted using Kolaskar and Tongaonkar antigenicity, Emini surface accessibility, and Parker hydrophilicity prediction in Immune Epitope Database (IEDB). Results showed that five (5) epitopes were consensus for DENV-1 with no detected unique epitope, one (1) consensus epitope for DENV-2 with two (2) unique epitopes, one (1) consensus epitope for DENV-3 plus two (2) unique epitopes, and two (2) consensus epitopes and one (1) unique epitope for DENV-4. The findings of this study would contribute to determining potential vaccine and diagnostic marker candidates for further research studies and immunological applications against DENV (1–4) Philippine isolates.

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“…Therefore, it should be further studied whether these variants could have any effect on viral fitness and ultimately on viral transmission from one compartment to the other. Overall, secondary structures described within the UTRs of different arboviruses seemed to be involved in viral replication but also pathogenesis (reviewed in [49,50]).…”

Section: In Silico Analysis Of Missense Mutationsmentioning

confidence: 99%

In Depth Viral Diversity Analysis in Atypical Neurological and Neonatal Chikungunya Infections in Rio de Janeiro, Brazil

Torres

Maio

Brown

et al. 2022

Viruses

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Chikungunya virus (CHIKV) is an arthropod-borne virus (arbovirus) transmitted by Aedes mosquitoes. The human infection usually manifests as a febrile and incapacitating arthritogenic illness, self-limiting and non-lethal. However, since 2013, CHIKV spreading through the tropics and to the Americas was accompanied by an increasing number of cases of atypical disease presentation, namely severe neuropathies and neonatal infection due to intrapartum vertical transmission. The pathophysiological mechanisms underlying these conditions have not been fully elucidated. However, arbovirus intrahost genetic diversity is thought to be linked to viral pathogenesis. To determine whether particular viral variants could be somehow associated, we analyzed the intrahost genetic diversity of CHIKV in three infected patients with neurological manifestations and three mothers infected during the intrapartum period, as well as their babies following vertical transmission. No statistically supported differences were observed for the genetic variability (nucleotide substitutions/gene length) along the genome between the groups. However, the newborn and cerebrospinal fluid samples (corresponding to virus passed through the placenta and/or the blood–brain barrier (BBB)) presented a different composition of their intrahost mutant ensembles compared to maternal or patient serum samples, even when concurrent. This finding could be consistent with the unidirectional virus transmission through these barriers, and the effect of selective bottlenecks during the transmission event. In addition, a higher proportion of defective variants (insertions/deletions and stop codons) was detected in the CSF and maternal samples and those were mainly distributed within the viral non-structural genes. Since defective viral genomes in RNA viruses are known to contribute to the outcome of acute viral infections and influence disease severity, their role in these atypical cases should be further investigated. Finally, with the in silico approach adopted, we detected no relevant non-conservative mutational pattern that could provide any hint of the pathophysiological mechanisms underlying these atypical cases. The present analysis represents a unique contribution to our understanding of the transmission events in these cases and generates hypotheses regarding underlying mechanisms, that can be explored further.

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In SilicoAnalysis of Dengue Virus Serotype 2 Mutations Detected at the Intrahost Level in Patients with Different Clinical Outcomes

Cited by 3 publications

References 97 publications

Assessment of genetic diversity patterns of different serotypes of dengue virus, prevalent in patients from Kerala, India: a strain specific mutation study and its relevance to pathogenesis

Assessment of genetic diversity patterns of different serotypes of dengue virus, prevalent in patients from Kerala, India: a strain specific mutation study and its relevance to pathogenesis

In Silico Comparative Analysis of Predicted B Cell Epitopes against Dengue Virus (Serotypes 1–4) Isolated from the Philippines

In Depth Viral Diversity Analysis in Atypical Neurological and Neonatal Chikungunya Infections in Rio de Janeiro, Brazil

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