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

Previous evidence showed that intrahost genetic diversity in arboviruses may be linked to viral pathogenesis and that one or a few amino acid replacements within a single protein are enough to modify a biological feature of an RNA virus. To assess 2 dengue virus determinants potentially involved in pathogenesis, we previously analyzed the intrahost genetic diversity of the virus in patients with different clinical outcomes and identified a set of 141 mutations that deserved further study. Thus, through a molecular modeling approach, we showed that disruptive variants were identified primarily among cases with mild dengue fever, while potential immune-escape variants were mainly associated with cases of greater severity.

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Identification of natural product compounds as NS5 RDRP inhibitor for dengue virus serotype 1-4 through in silico analysis

10.1063/5.0005236 ◽

2020 ◽

Author(s):

Hersal Hermana Putra ◽

Mutiara Saragih ◽

Yulianti ◽

Usman Sumo Friend Tambunan

Keyword(s):

Dengue Virus ◽

Natural Product ◽

In Silico ◽

In Silico Analysis ◽

Virus Serotype ◽

Serotype 1 ◽

Natural Product Compounds ◽

Silico Analysis ◽

Dengue Virus Serotype 1

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Dengue Virus Serotype 2 Intrahost Diversity in Patients with Different Clinical Outcomes

Viruses ◽

10.3390/v13020349 ◽

2021 ◽

Vol 13 (2) ◽

pp. 349

Author(s):

Maria Celeste Torres ◽

Marcos Cesar Lima de Mendonça ◽

Cintia Damasceno dos Santos Rodrigues ◽

Vagner Fonseca ◽

Mario Sergio Ribeiro ◽

...

Keyword(s):

Genetic Diversity ◽

Clinical Outcome ◽

Dengue Virus ◽

Warning Signs ◽

Viral Population ◽

Severe Dengue ◽

Clinical Samples ◽

Pathogenic Potential ◽

Virus Serotype ◽

Dengue Virus Serotype 2

Intrahost genetic diversity is thought to facilitate arbovirus adaptation to changing environments and hosts, and it might also be linked to viral pathogenesis. Dengue virus serotype 2 (DENV-2) has circulated in Brazil since 1990 and is associated with severe disease and explosive outbreaks. Intending to shed light on the viral determinants for severe dengue pathogenesis, we sought to analyze the DENV-2 intrahost genetic diversity in 68 patient cases clinically classified as dengue fever (n = 31), dengue with warning signs (n = 19), and severe dengue (n = 18). Unlike previous DENV intrahost diversity studies whose approaches employed PCR, here we performed viral whole-genome deep sequencing from clinical samples with an amplicon-free approach, representing the real intrahost diversity scenario. Striking differences were detected in the viral population structure between the three clinical categories, which appear to be driven mainly by different infection times and selection pressures, rather than being linked with the clinical outcome itself. Diversity in the NS2B gene, however, showed to be constrained, irrespective of clinical outcome and infection time. Finally, 385 non-synonymous intrahost single-nucleotide variants located along the viral polyprotein, plus variants located in the untranslated regions, were consistently identified among the samples. Of them, 124 were exclusively or highly detected among cases with warning signs and among severe cases. However, there was no variant that by itself appeared to characterize the cases of greater severity, either due to its low intrahost frequency or the conservative effect on amino acid substitution. Although further studies are necessary to determine their real effect on viral proteins, this heightens the possibility of epistatic interactions. The present analysis represents an initial effort to correlate DENV-2 genetic diversity to its pathogenic potential and thus contribute to understanding the virus’s dynamics within its human host.

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