Background

Contents

• Overview
• Advances in Parvovirus Discovery
• Comparative Genomics and Parvovirus Research
• Parvovirus-GLUE and Comparative Genomics

Overview

Parvovirus-GLUE is a specialized resource designed to facilitate comparative analysis of parvovirus genomes, built within the GLUE software framework.

Parvoviruses are a diverse group of small, non-enveloped DNA viruses that infect a wide variety of animal species, including many that are of significant medical and veterinary importance. The parvovirus family encompasses numerous pathogens affecting humans and domesticated animals, causing diseases such as canine parvoviral enteritis and parvovirus B19.

Beyond their role as pathogens, parvoviruses are also emerging as next-generation therapeutic tools. One parvovirus, group - the adeno-associated viruses (AAVs) - have been successfully developed as gene therapy vectors and are at the forefront of advancements in human gene therapy. In addition, rodent protoparvoviruses demonstrate natural oncotropism and oncolytic properties, making them promising candidates for cancer treatment.

Comparative genomics plays a crucial role in parvovirus research by enabling scientists to identify genetic variations across different parvovirus strains and species. This approach helps in understanding viral evolution, host specificity, and pathogenicity. By comparing the genomes of parvoviruses, researchers can uncover key genetic features that influence virulence, immune evasion, and tissue tropism—insights that are invaluable both for understanding disease mechanisms and for optimizing the design of gene therapy vectors or oncolytic agents.

The GLUE software framework provides an extensible platform for implementing comparative genomic analysis of viruses in an efficient, standardised and reproducible way. GLUE projects not only integrate key data items such as sequences, alignments, and genome feature annotations, but also establish complex semantic links between these data items using a relational database. This structure prepares sequences and their associated data for computational analysis, minimizing the need for labor-intensive pre-processing and enabling streamlined workflows.

Advances in Parvovirus Discovery

In recent years, high-throughput sequencing and new metagenomic methods have led to the discovery of numerous novel parvovirus species. Furthermore, progress in whole genome sequencing (WGS) has revealed that DNA sequences derived from parvoviruses commonly occur in animal genomes as endogenous viral elements. The availability of sequence data from a wide range of diverse parvovirus species provides unprecedented opportunities to utilise comparative approaches to investigate parvovirus biology.

Some of the species in which novel parvoviruses and endogenous parvoviral elements (EPVs) have been identified.
Top row, left to right: Masai giraffe (Giraffa camelopardalis tippelskirchii), Tasmanian devil (Sarcophilus harrisii), elephants (Elephantidae), chinchilla (Chinchilla lanigera).
Bottom row, left to right: Northern fur seals (Callorhinus ursinus), pit vipers (Crotalinae), Leadbetter's possum (Gymnobelideus leadbeateri), Transcaucasian mole vole (Ellobius lutescens).

Comparative Genomics and Parvovirus Research

Comparative genomics is a powerful approach for understanding the diversity, evolution, and functional biology of viruses. By comparing parvovirus genomes, researchers can gain insights into evolutionary history, host-virus interactions, and mechanisms of pathogenicity.

1. Evolution & Phylogeny: Genome comparisons allow reconstruction of virus evolutionary history, and thereby facilitate understanding of parvovirus distribution and diversity.

2. Host Range & Adaptation: Comparisons can identify viral traits for host specificity and adaptations that allow parvoviruses to infect new species.

3. Tropism & Pathogenesis: By comparing virus strains, researchers can uncover genetic factors determining tissue specificity and pathogenicity.

4. Immune Evasion: Identification of mutation hotspots and antigenic variation can inform vaccine development and understanding of viral evolution under immune pressure.

5. Functional Genomics: Genomic comparisons can highlight functional elements and protein structure-function relationships critical for viral replication.

6. Genomic Conservation: Conserved regions important for viral function are identified for drug or vaccine targeting, while variable regions help understand viral adaptation.

7. Vaccine & Therapeutic Development: Identifying conserved elements aids in developing broad-spectrum vaccines, while optimizing gene therapy vectors (e.g., AAVs) through comparative analysis.

8. Epidemiology: Genomic comparisons help track viral spread, detect emerging strains, and guide outbreak responses and vaccine updates.

9. Paleovirology: EVEs provide a historical record of past infections. Comparisons of EVEs and virus genomes can reveal ancient viral genomes, revealing long-term viral evolution.

Parvovirus-GLUE and Comparative Genomics

Parvovirus-GLUE aims to enable researchers to perform large-scale comparative genomic analyses by providing access to standardized datasets of parvovirus genomes, combined with analysis tools.

Parvovirus-GLUE can be customized to focus on specific genera or species of parvoviruses, allowing researchers to tailor their analyses to particular research questions, such as the evolution of dependoparvoviruses (e.g., AAVs) or amdoparvoviruses (e.g., Aleutian mink disease virus).