"Endogenous retroviruses (ERVs) are DNA fragments found dispersed in a wide range of genomes, from invertebrates to mammals, that resemble members of the Retroviridae viral family (termed here exogenous retroviruses or XRVs). Because XRV replication involves integration into the host chromosome, it is generally assumed that ERVs are the result of ancient XRV infections, which have passed into the germ-line of the host and expanded within it. ERVs are classified into three classes, while XRVs are classified into subfamilies and genera. Class-I ERVs and Gammaretroviruses are phylogenetically close. Therefore, Class-I ERVs are suggested to be the million-years archive of the Gammaretrovirus infections. I propose to study the viral and host factors that have affected the cross-species transmission history of Gammaretroviruses by studying the relationships between Gammaretroviruses and Class-I ERVs. I will use a bioinformatics’ approach to mine all the available mammalian genomes and extract all the Class-I ERVs. Then, I will build a phylogenetic tree containing all the available Gammaretroviruses and Class-I ERVs to clarify their relationships. I will use the tree to discriminate between shared invasions and cross-species transmission (CST) events. I will implement statistical and phylogenetic methods to clarify if recombination or integrity of the env gene has enhanced or suppressed CST, respectively. I will also look at the protein receptors known to be used by some Gammaretroviruses and correlate their presence and phylogeny in the hosts with the CST events. Moreover, I will look the development of innate antiretroviral resistance mechanisms in the phylogeny of hosts and correlate this with the presence of Class-I ERVs or Gammaretroviruses. Finally, I will study the adaptation that has occurred following the CST events. The project will provide insights into how retroviruses move between hosts, a phenomenon with important Public Health implications."
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