Genome-endogenated viruses Flashcards
How do endogenous retroviruses gain access to cellular DNA
via transport of pre-integration complex into nucleus
How does the pre-integration complex edit the hosts genome
i. Integrasecuts the DNA of the cell chromosome in two and insert the provirus gene in between.
ii. Integration of provirus gene with cell DNA is mediated by cell DNA repair machinery.
iii. Integration could result in productive infection (immediate virus gene expression) or latent infection (delayed virus gene expression).
iv. When host cells with latent infection divide, the provirus gene is retained along with cell genome in each daughter cell.
How are ERVs identified
- Sequencing of the genome of vertebrate animals has enabled the identification of endogenatedretrovirus (ERV) genes.
- For example, sequencing of the human genome have shown the presence of about 100,000 human endogenatedretrovirus (HERV) sequences.
- Most of the incorporated genome of endogenatedretroviruses are defectiv
ERVs vs Exogenous retroviruses
- ERVs have been observed to show similarity in genome sequences to the exogenatedretroviruses (retroviruses infecting new host cells from the external environment).
- For example, genome sequencing have shown high level similarity between ERV sequences in micewith that of the genome of mouse mammary tumor virus.
Orgin of ERVs
- ERVs originated from exogenatedretroviruses infecting germ line cells (egg and/or sperm cells): Speculation was based on sequence similarity between ERVs and exogenatedretroviruses coupled with the high number of ERVs in vertebrate genome.
- The high number of ERVs in vertebrate genome could be due to the presence of a copy of the provirus gene in each of the cells in the offspring’s body arising from reproductive process involving the germ line infected with the provirus
Retrotransposition
- A process whereby ERV genes are copied to other locations in the genome over time resulting in families of related ERVs.
- The process of gene copying is controlled by ERVs and other genome elements referred to as retrotransposons.
Stimulation of ERVs
- Infectious agents: most ERVs remain inactive in host genome for most times, but could be activated by other infectious agents.
- Activation of ERVs could result to transcription and translation into virionproteins.
What happens when ERVs are activated
- Presence of full complement of the retroviral gene: may result in an ERV particle if the full complement of the retroviral gene is available during ERV activation.
- Supply of an essential ERV gene by a second ERV or an exogenous retrovirus: Also, an ERV particle may result if the missing gene is supplied by another ERV or by an exogenous retrovir
Replication of ERVs in animal models
- Some ERVs don’t replicate in cells of the same animal species which they occur, but can in other animal species during tissue transplant.
- For instance, some pig ERVs and mouse ERVs have the capacity to replicate in human cells.
- This observation suggests that pig retroviruses can be transmitted to humans if infected animal cells and tissues are transplanted into humans during a transplant
Beneficial ERV proteins
•Research evidence suggests that vertebrate animals might have harnessed some ERV proteins for their benefit. For instance, the ability of ERV envelope proteins to fuse membranes have been shown to be exploited in the development of the placenta in some mammalian specie