Evaluation of potential MHC-I allele-specific epitopes in Zika virus proteins and the effects of mutations on peptide-MHC-I interaction studied using in silico approaches

The disease caused by the Zika virus (ZIKV) has positioned itself as one of the main public health problems in Mexico. One of the main reasons is it causes microcephaly and other birth defects. The transmission of ZIKV is through Aedes aegypti and Ae. albopictus mosquitoes, which are found in a larger space of the national territory. In addition, it can also be transmitted via blood transfusion, sexual relations, and maternal-fetal route. So far, there are no vaccines or specific treatments to deal with this infection. Currently, some new therapeutics such as small interfering RNAs (siRNAs) are able to regulate or suppress transcription in viruses. Therefore, in this project, an in silico siRNA was designed for the 3′UTR region of ZIKV via bioinformatics tools. The designed siRNA was synthesized and transfected into the C6/36 cell line, previously infected with ZIKV in order to assess the ability of the siRNA to inhibit viral replication. The designed siRNA was able to inhibit significantly (p<0.05) ZIKV replication; this siRNA could be considered a potential therapeutic towards the disease that causes ZIKV and the medical problems generated.

Download Full-text

Prediction of promiscuous T-cell epitopes in the Zika virus polyprotein: An in silico approach

Asian Pacific Journal of Tropical Medicine ◽

10.1016/j.apjtm.2016.07.004 ◽

2016 ◽

Vol 9 (9) ◽

pp. 844-850 ◽

Cited By ~ 26

Author(s):

Hamza Dar ◽

Tahreem Zaheer ◽

Muhammad Talha Rehman ◽

Amjad Ali ◽

Aneela Javed ◽

...

Keyword(s):

T Cell ◽

Zika Virus ◽

In Silico ◽

T Cell Epitopes ◽

Virus Polyprotein

Download Full-text

A Reverse Genetics System for Zika Virus Based on a Simple Molecular Cloning Strategy

Viruses ◽

10.3390/v10070368 ◽

2018 ◽

Vol 10 (7) ◽

pp. 368 ◽

Cited By ~ 16

Author(s):

Maximilian Münster ◽

Anna Płaszczyca ◽

Mirko Cortese ◽

Christopher Neufeldt ◽

Sarah Goellner ◽

...

Keyword(s):

Zika Virus ◽

In Silico ◽

Reverse Genetics ◽

Molecular Mechanisms ◽

Full Length ◽

Cdna Clones ◽

In Silico Prediction ◽

Fluorescent Reporter ◽

Full Length Cdna ◽

Spurious Transcription

The Zika virus (ZIKV) has recently attracted major research interest as infection was unexpectedly associated with neurological manifestations in developing foetuses and with Guillain-Barré syndrome in infected adults. Understanding the underlying molecular mechanisms requires reverse genetic systems, which allow manipulation of infectious cDNA clones at will. In the case of flaviviruses, to which ZIKV belongs, several reports have indicated that the construction of full-length cDNA clones is difficult due to toxicity during plasmid amplification in Escherichia coli. Toxicity of flaviviral cDNAs has been linked to the activity of cryptic prokaryotic promoters within the region encoding the structural proteins leading to spurious transcription and expression of toxic viral proteins. Here, we employ an approach based on in silico prediction and mutational silencing of putative promoters to generate full-length cDNA clones of the historical MR766 strain and the contemporary French Polynesian strain H/PF/2013 of ZIKV. While for both strains construction of full-length cDNA clones has failed in the past, we show that our approach generates cDNA clones that are stable on single bacterial plasmids and give rise to infectious viruses with properties similar to those generated by other more complex assembly strategies. Further, we generate luciferase and fluorescent reporter viruses as well as sub-genomic replicons that are fully functional and suitable for various research and drug screening applications. Taken together, this study confirms that in silico prediction and silencing of cryptic prokaryotic promoters is an efficient strategy to generate full-length cDNA clones of flaviviruses and reports novel tools that will facilitate research on ZIKV biology and development of antiviral strategies.

Download Full-text