A Mathematical Analysis of HDV Genotypes: From Molecules to Cells.

Rami Zakh,Marina Parr,Tamir Tuller,Danny Barash,Harel Dahari,Dmitrij Frishman,Alexander Churkin,Ohad Etzion,Michael Roggendorf,Franziska Totzeck

doi:10.3390/math9172063

Abstract

Hepatitis D virus (HDV) is classified according to eight genotypes. The various genotypes are included in the HDVdb database, where each HDV sequence is specified by its genotype. In this contribution, a mathematical analysis is performed on RNA sequences in HDVdb. The RNA folding predicted structures of the Genbank HDV genome sequences in HDVdb are classified according to their coarse-grain tree-graph representation. The analysis allows discarding in a simple and efficient way the vast majority of the sequences that exhibit a rod-like structure, which is important for the virus replication, to attempt to discover other biological functions by structure consideration. After the filtering, there remain only a small number of sequences that can be checked for their additional stem-loops besides the main one that is known to be responsible for virus replication. It is found that a few sequences contain an additional stem-loop that is responsible for RNA editing or other possible functions. These few sequences are grouped into two main classes, one that is well-known experimentally belonging to genotype 3 for patients from South America associated with RNA editing, and the other that is not known at present belonging to genotype 7 for patients from Cameroon. The possibility that another function besides virus replication reminiscent of the editing mechanism in HDV genotype 3 exists in HDV genotype 7 has not been explored before and is predicted by eigenvalue analysis. Finally, when comparing native and shuffled sequences, it is shown that HDV sequences belonging to all genotypes are accentuated in their mutational robustness and thermodynamic stability as compared to other viruses that were subjected to such an analysis.

Highlights

IntroductionSpecific functions of RNA structure motifs have been examined in many viruses (for example, in the hepatitis C virus (HCV) [3,4,5]) by combining computational and experimental approaches
The first component relies on filtering rod-like structures that are dominant in Hepatitis D virus (HDV) because they correspond to virus replication
The following table reports an eigenvalue analysis of all HDV genome sequences in [42] by calculating their second-smallest eigenvalue of the Laplacian matrix corresponding to the tree-graph representation of their folding prediction as illustrated in

Summary

Introduction

Specific functions of RNA structure motifs have been examined in many viruses (for example, in the hepatitis C virus (HCV) [3,4,5]) by combining computational and experimental approaches. A large percentage of viral RNA motifs tend to possess linear secondary structures similar to the ones depicted in [7], which are often stem-loop structures designated by SL for their identification. Stem-loop structural motifs have been investigated in our previous article [9]. This contribution is a continuation of [9] that considers hepatitis delta virus (HDV), which has the smallest human viral genome and uses the envelope of hepatitis B virus (HBV) to generate infectious particles.

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