Retrovirus Projects
Retroviruses are a unique group of RNA viruses that replicate through a process of reverse transcription, integrating their genetic material into the host genome. This integration allows them to persist as proviruses, blurring the line between infectious agents and endogenous elements within the host's genetic material. Retroviruses, such as human immunodeficiency virus (HIV) and human T-lymphotropic virus (HTLV), are best known for their role in causing significant human diseases. However, their study extends beyond traditional virology, as they exist at the interface of infectious agents and genetic elements, reflecting their dual nature as both viruses and molecular components of host genomes. Their capacity for long-term integration enables retroviruses to drive genetic evolution, influencing gene expression and the genomic architecture of host organisms.
This interface between infection and host biology positions retroviruses as a focal point not only in the study of viral pathogenesis but also in understanding fundamental biological processes. Endogenous retroviruses (ERVs), which are the remnants of ancient retroviral infections, comprise a significant portion of vertebrate genomes, contributing to host evolution and playing important roles in immunity, reproduction, and gene regulation. Retroviral research bridges virology and whole-organism biology, providing insights into viral-host co-evolution, the origins of genomic innovations, and the mechanisms underlying viral persistence and immune evasion. The study of retroviruses, therefore, encompasses both their role as pathogens and as long-term genomic elements, making them critical to fields ranging from molecular evolution to cancer biology and gene therapy
Retroviruses have long been the central focus of research in the Gifford Lab, and the motivation for developing GLUE was in large part driven by the need for a systematic approach to organising and analyze endogenous retrovirus (ERV) data. Recognizing the overlap between the techniques required for ERV studies and those used in broader viral analyses, such as genomic epidemiology, informed the design of GLUE. This vision for GLUE embraces the synergy between different areas of virus research, seeking to enable collaborative use of data and analysis techniques across diverse scientific contexts. By fostering a flexible framework for shared methodologies, GLUE facilitates the study of retroviruses in a comparative genomics context, while extending its utility to support broader virology and evolutionary biology investigations.
This page provides a comprehensive list of GLUE projects developed for retroviruses in the Gifford Lab:
- Lentiviruses: Lentivirus-GLUE
- Deltaretroviruses: Deltaretrovirus-GLUE
Lentivirus-GLUE is a specialized resource designed to support the support comparative genomic and evolutionary analysis of lentiviruses. Lentiviruses are complex retroviruses that cause chronic diseases in humans and animals, with HIV being the most well-known example. Their high variability and ability to evade the immune system make them particularly challenging to manage and treat.
Lentivirus GLUE was first developed as an HIV project, and later expanded to encompass all lentiviruses, including ERVs.
The HIV and primate lentivirus components were developed as part of the research activities of the Centre for HIV RNA Studies (CRNA) from 2017-2022.
The small ruminant lentivirus (SRLV) extension was developed in association with an investigation into the origin and emergence of pandemic SRLV infection, published in 2023.
The ERV components were compiled in association with the discovery of Springhare endogenous lentivirus, a lentiviral ERV identified in the genome of a rodent. This study included comprehensive mapping of lentivirus ERVs in published whole genome sequence (WGS) assemblies.
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Comprehensive Genomic Database: Integrates data from all known lentivirus sequences, including species-specific NCBI extension projects that add all lentivirus sequences in GenBank, providing a robust foundation for comparative genomics research.
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Genotyping: MLCA-based assignment of genotypes and subtypes.
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Translation Engine: Models ribosomal frameshifting, supporting accurate translation for all retrovirus species, including lentiviruses, to ensure precise protein-level analysis.
| Property | Description |
|---|---|
| Scope | Lentiviruses (genus Lentivirus) |
| Development Period | 2018-2024 |
| Lead Developers | Robert J. Gifford |
| Main Objectives | Comparative genomics, Molecular epidemiology |
| Data Sources | NCBI |
| Associated Tools | BLAST+, MAFFT, RAXML |
| Offline Project | GitHub |
| Online Access | None as yet |
| Status | Mature. Actively being developed |
| User Guide | GitHub Wiki |
Lentivirus-GLUE can be extended with additional layers, openly available via GitHub, including:
- Lentivirus-GLUE-Primates: adds all NCBI sequence data for primate lentiviruses, including HIV-1 and HIV-2.
- Lentivirus-GLUE-SRLV: small ruminant lentiviruses (SRLVs), adds all NCBI sequence data plus curated metatdata and analysis logic.
- Lentivirus-GLUE-EIAV: equine infectious anemia virus (EIAV), adds all NCBI sequence data.
- Lentivirus-GLUE-FIV: feline immunodeficiency viruses (FIVs), adds all NCBI sequence data.
- Lentivirus-GLUE-ERV: adds lentivirus sequences that occur as endogenous retroviruses (ERVs).
Deltaretroviruses are a group of retroviruses that primarily infect mammals, including humans. They are characterized by their ability to establish lifelong infections, often leading to severe diseases such as leukemia and lymphoma. Notable deltaretroviruses include Human T-lymphotropic virus type 1 (HTLV-1), which causes adult T-cell leukemia/lymphoma (ATLL), and Bovine Leukemia Virus (BLV), which induces leukemia in cattle.
Deltaretrovirus-GLUE was originally developed to support paleovirological investigations of Deltaretrovirus-derived ERVs. It was later expanded to incorporate all published deltaretrovirus sequences.
- Comprehensive Genomic Database: Integrates data from all known lentivirus sequences, including species-specific NCBI extension projects that add all lentivirus sequences in GenBank, providing a robust foundation for comparative genomics research.
| Property | Description |
|---|---|
| Scope | Deltaretroviruses (genus Deltaretrovirus) |
| Development Period | 2018-2024 |
| Lead Developers | Robert J. Gifford |
| Main Objectives | Comparative genomics, Molecular epidemiology |
| Data Sources | NCBI |
| Associated Tools | BLAST+, MAFFT, RAXML |
| Offline Project | GitHub |
| Online Access | None as yet |
| Status | Mature. Not currently being developed |
| User Guide | None yet |
GLUE by Robert J. Gifford Lab.
For questions, issues, or feedback, please open an issue on the GitHub repository.