Genome invasion: understanding the evolutionary and functional roles of mutation and recombination at the earliest stages of retroviral endogenization

• Applicant: Professor Alex Greenwood, Ph.D.
• Subject Area: Virology ; Evolutionary Cell and Developmental Biology (Zoology) ; Microbial Ecology and Applied Microbiology ; Ecology and Biodiversity of Animals and Ecosystems, Organismic Interactions
• Term: from 2018 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 390597785

Vertebrate genomes are generally considered to be composed of genes and non-coding sequences that are either evolving under various forms of natural selection or are evolving neutrally. However, a very large component of the vertebrate genome (8% in humans) is composed of sequences deriving from retroviruses The overall objective of this proposal is to understand the role envelope altering mutations and recombination play in altering receptor tropism and virulence during the conversion of exogenous retroviruses to endogenous retroviruses (ERVs) using the Koala retrovirus (KoRV)/gibbon ape leukemia virus (GALV) viral clade as a model. This will allow us to understand how almost 10% of vertebrate genomes have been formed by infectious agents, using two viral groups containing some of the youngest known and not fully endogenized ERVs. This will entail identifying, as comprehensively as possible, GALV and KoRV virus diversity across their potential host range, identifying variation in functional motifs involved in viral entry (receptor) and replication and testing identified differences functionally in cell culture based systems.Objective 1: The rodent genus Melomys of Indonesia, Papua New Guinea and Australia are the only non gibbon or Koala species found to carry GALV/KoRV like viruses, though only 3 of 24 species have been tested. The genus will be fully screened for KoRV and GALV. Objective 2: The Wallace Line is a geographical barrier between Southeast Asia and much of Indonesia, Papau New Guinea and Australia. We will screen mammals that have successfully crossed the Wallace Line for GALV and KoRV like sequencesObjective 3: Identify functional significance of non-synonymous GAG and ENV differences in a heterologous retroviral expression system.

• DFG Programme: Research Grants