Multiple groups of endogenous epsilon-like retroviruses conserved across primates

Several types of cancer in fish are caused by retroviruses, including those responsible for major outbreaks of disease, such as walleye dermal sarcoma virus and salmon swim bladder sarcoma virus. These viruses form a phylogenetic group often described as the epsilonretrovirus genus. Epsilon-like retroviruses have become endogenous retroviruses (ERVs) on several occasions, integrating into germ line cells to become part of the host genome, and sections of fish and amphibian genomes are derived from epsilon-like retroviruses. However, epsilon-like ERVs have been identified in very few mammals. We have developed a pipeline to screen full genomes for ERVs, and using this pipeline, we have located over 800 endogenous epsilon-like ERV fragments in primate genomes. Genomes from 32 species of mammals and birds were screened, and epsilon-like ERV fragments were found in all primate and tree shrew genomes but no others. These viruses appear to have entered the genome of a common ancestor of Old and New World monkeys between 42 million and 65 million years ago. Based on these results, there is an ancient evolutionary relationship between epsilon-like retroviruses and primates. Clearly, these viruses had the potential to infect the ancestors of primates and were at some point a common pathogen in these hosts. Therefore, this result raises questions about the potential of epsilonretroviruses to infect humans and other primates and about the evolutionary history of these retroviruses. IMPORTANCE: Epsilonretroviruses are a group of retroviruses that cause several important diseases in fish. Retroviruses have the ability to become a permanent part of the DNA of their host by entering the germ line as endogenous retroviruses (ERVs), where they lose their infectivity over time but can be recognized as retroviruses for millions of years. Very few mammals are known to have epsilon-like ERVs; however, we have identified over 800 fragments of endogenous epsilon-like ERVs in the genomes of all major groups of primates, including humans. These viruses seem to have circulated and infected primate ancestors 42 to 65 million years ago. We are now interested in how these viruses have evolved and whether they have the potential to infect modern humans or other primates

Characterisation of endogenous retroviruses in the saltwater crocodile (Crocodylus porosus)

Amanda CHONG Characterisation of endogenous retroviruses in the saltwater crocodile (Crocodylus porosus) Endogenous retroviruses (ERVs) are a diverse group of vertebrate transposable elements, and are derived from germline infections by exogenous retroviruses. Very few studies have been carried out investigating the diversity of ERVs in non-mammalian vertebrates despite evidence that these species harbour a diverse and divergent ERV complement. This project constitutes the first comprehensive investigation of endogenous retroviruses (ERVs) in crocodilians. The research presented herein encompasses the characterisation of crocodilian ERVs from key crocodilian species, and explores the evolutionary dynamics of these ERVs within their host genomes. It also offers insights into the evolution of ERVs and exogenous retroviruses. Overall, this project has demonstrated that crocodilians, and likely other non-mammalian vertebrates, are a rich source of novel ERV diversity, and may provide unique insights into the evolution of modern exogenous retroviruses and their hosts. It has also highlighted the relative merits of a wide variety of ERV detection techniques, both molecular and bioinformatic, and how these may be adapted for studies of previously uncharacterised taxa. This project will provide a useful resource to facilitate further investigations into the significance of ERVs in crocodilian biology, and offers insights into how these approaches may be translated to studies of other vertebrate taxa

Endogenous retroviruses in primates

Numerous endogenous retroviruses (ERVs) are found in all mammalian genomes and represent retroviruses which have, by chance, integrated into the germline and are transmitted vertically from parents to offspring. In many non-human primates these insertions have not been well-studied. ERVs provide a snapshot of the retroviruses a host has been exposed to during its evolutionary history, including retroviruses which are no longer circulating. Accurate annotation and characterisation of ERV regions is an important step in interpreting the huge amount of genetic information available for increasing numbers of organisms. This project represents an extensive study into the diversity of ERVs in the genomes of primates and related ERVs in rodents, lagomorphs and tree shrews. The focus is on groups of ERVs for which previous analyses are patchy or outdated, particularly in terms of their evolutionary history and possible transmission routes. A pipeline has been developed to comprehensively and rapidly screen genomes for ERVs and phylogenetic analysis has been performed in order to characterise these ERVs. Laboratory study was used to complement the bioinformatics analysis. Almost 200,000 ERV fragments, many of which have not previously been characterised, were identified. A novel endogenous member of the lentivirus genus of retroviruses, which are rarely found in an endogenous form, was identified in the bushbaby Galago moholi. This ERV may represent an ancient ancestor of modern human immunodeficiency virus (HIV). Another retrovirus, gibbon ape leukaemia virus, previously thought to be a common pathogen in gibbons, was found to not exist in contemporary gibbons and a route through which a single cross species transmission event may have resulted in all known cases of this disease worldwide was identified. Endogenous epsilonretroviruses, usually considered to be viruses of fish and amphibians, were identified in all screened species of primates

Endogenous retroviruses in primates

Numerous endogenous retroviruses (ERVs) are found in all mammalian genomes and represent retroviruses which have, by chance, integrated into the germline and are transmitted vertically from parents to offspring. In many non-human primates these insertions have not been well-studied. ERVs provide a snapshot of the retroviruses a host has been exposed to during its evolutionary history, including retroviruses which are no longer circulating. Accurate annotation and characterisation of ERV regions is an important step in interpreting the huge amount of genetic information available for increasing numbers of organisms. This project represents an extensive study into the diversity of ERVs in the genomes of primates and related ERVs in rodents, lagomorphs and tree shrews. The focus is on groups of ERVs for which previous analyses are patchy or outdated, particularly in terms of their evolutionary history and possible transmission routes. A pipeline has been developed to comprehensively and rapidly screen genomes for ERVs and phylogenetic analysis has been performed in order to characterise these ERVs. Laboratory study was used to complement the bioinformatics analysis. Almost 200,000 ERV fragments, many of which have not previously been characterised, were identified. A novel endogenous member of the lentivirus genus of retroviruses, which are rarely found in an endogenous form, was identified in the bushbaby Galago moholi. This ERV may represent an ancient ancestor of modern human immunodeficiency virus (HIV). Another retrovirus, gibbon ape leukaemia virus, previously thought to be a common pathogen in gibbons, was found to not exist in contemporary gibbons and a route through which a single cross species transmission event may have resulted in all known cases of this disease worldwide was identified. Endogenous epsilonretroviruses, usually considered to be viruses of fish and amphibians, were identified in all screened species of primates

TRIM proteins and CXS chemokines : evolutionary dynamics and functional characterization of two large protein families in teleost fish

Two large protein families with roles in the immune system were the subject of this thesis. In part one of the thesis, TRIM proteins were studied, which are part of an ancient intracellular immune system. In mammals, TRIM proteins were recently found to play an important role in the antiviral immune response as they can restrict multiple viruses. To better understand the evolution of the TRIM protein family, TRIM proteins were investigated in teleost fish, which emerged early during vertebrate evolution. A detailed description of the entire TRIM gene family in fish was made and it was discovered that certain TRIM genes have undergone a radical expansion, giving rise to three multigene families. Experimental studies indicated a role for trout TRIM proteins in antiviral immunity and demonstrated that they have E3 ubiquitin ligase activity. As it recently became evident that ubiquitination is an important mode to control the activity of proteins of innate immune pathways, possibly TRIM proteins in fish have a similar activity. In part two of this thesis, inflammatory CXC chemokines were studied, for which limited functional data was available in fish at the start of the thesis project. CXC chemokines are specialized cytokines that direct leukocyte migration during inflammation. In zebrafish and carp, two CXC lineages were identified that resemble mammalian CXCL8, a similar diversification was observed for chemokines that resemble mammalian CXCL9, CXCL10, CXCL11chemokines. A characterization of the functions for cyprinid CXCL8-like and CXCL9-11-like (named CXCb) chemokines was made by in vitro and in vivo gene expression studies. By preparation of recombinant proteins it was demonstrated that carp chemokines of the CXCL8-like and CXCb subsets are both chemotactic for fish leukocytes. Chemokines of the CXCL8-like and CXCb subsets appeared to be functionally distinct, as they have a different effect on phagocyte activation and act during different phases of the inflammatory response. These results indicate that CXC chemokines have already specialized functions in fish. </p