George Robert Young

Publications (4) View all

• Article: Resurrection of endogenous retroviruses in antibody-deficient mice.

  George R Young, Urszula Eksmond, Rosalba Salcedo, Lena Alexopoulou, Jonathan P Stoye, George Kassiotis
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  ABSTRACT: The mammalian host has developed a long-standing symbiotic relationship with a considerable number of microbial species. These include the microbiota on environmental surfaces, such as the respiratory and gastrointestinal tracts, and also endogenous retroviruses (ERVs), comprising a substantial fraction of the mammalian genome. The long-term consequences for the host of interactions with these microbial species can range from mutualism to parasitism and are not always completely understood. The potential effect of one microbial symbiont on another is even less clear. Here we study the control of ERVs in the commonly used C57BL/6 (B6) mouse strain, which lacks endogenous murine leukaemia viruses (MLVs) able to replicate in murine cells. We demonstrate the spontaneous emergence of fully infectious ecotropic MLV in B6 mice with a range of distinct immune deficiencies affecting antibody production. These recombinant retroviruses establish infection of immunodeficient mouse colonies, and ultimately result in retrovirus-induced lymphomas. Notably, ERV activation in immunodeficient mice is prevented in husbandry conditions associated with reduced or absent intestinal microbiota. Our results shed light onto a previously unappreciated role for immunity in the control of ERVs and provide a potential mechanistic link between immune activation by microbial triggers and a range of pathologies associated with ERVs, including cancer.
  Nature 10/2012; · 36.28 Impact Factor
• Source

  Available from: PubMed Central

  Article: Negative selection by an endogenous retrovirus promotes a higher-avidity CD4+ T cell response to retroviral infection.

  George R Young, Mickaël J-Y Ploquin, Urszula Eksmond, Munisch Wadwa, Jonathan P Stoye, George Kassiotis
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  ABSTRACT: Effective T cell responses can decisively influence the outcome of retroviral infection. However, what constitutes protective T cell responses or determines the ability of the host to mount such responses is incompletely understood. Here we studied the requirements for development and induction of CD4+ T cells that were essential for immunity to Friend virus (FV) infection of mice, according to their TCR avidity for an FV-derived epitope. We showed that a self peptide, encoded by an endogenous retrovirus, negatively selected a significant fraction of polyclonal FV-specific CD4+ T cells and diminished the response to FV infection. Surprisingly, however, CD4+ T cell-mediated antiviral activity was fully preserved. Detailed repertoire analysis revealed that clones with low avidity for FV-derived peptides were more cross-reactive with self peptides and were consequently preferentially deleted. Negative selection of low-avidity FV-reactive CD4+ T cells was responsible for the dominance of high-avidity clones in the response to FV infection, suggesting that protection against the primary infecting virus was mediated exclusively by high-avidity CD4+ T cells. Thus, although negative selection reduced the size and cross-reactivity of the available FV-reactive naïve CD4+ T cell repertoire, it increased the overall avidity of the repertoire that responded to infection. These findings demonstrate that self proteins expressed by replication-defective endogenous retroviruses can heavily influence the formation of the TCR repertoire reactive with exogenous retroviruses and determine the avidity of the response to retroviral infection. Given the overabundance of endogenous retroviruses in the human genome, these findings also suggest that endogenous retroviral proteins, presented by products of highly polymorphic HLA alleles, may shape the human TCR repertoire that reacts with exogenous retroviruses or other infecting pathogens, leading to interindividual heterogeneity.
  PLoS Pathogens 05/2012; 8(5):e1002709. · 9.13 Impact Factor
• Source

  Available from: PubMed Central

  Article: Emv2, the only endogenous ecotropic murine leukemia virus of C57BL/6J mice.

  George R Young, George Kassiotis, Jonathan P Stoye
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  ABSTRACT: With the proliferation of sequence data, great challenges are posed in the correct annotation of endogenous retroviruses, which together comprise up to ten per cent of the genomes of many organisms. It is therefore essential that all sources of information are carefully considered before drawing conclusions concerning the phylogeny, distribution and biological properties of endogenous retroviruses. We suggest that such due diligence has not been applied in the description of an endogenous ecotropic retrovirus that recently appeared in Retrovirology.
  Retrovirology 03/2012; 9:23. · 6.47 Impact Factor
• Article: The timing of gonadal development and moult in three raptors with different breeding seasons: effects of gender, age and body condition

  GR Young, A Dawson, I Newton, L Walker
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  ABSTRACT: Differences between species in breeding seasons are thought to be mediated through differences in their reproductive physiology. Little is known about how the timing and duration of gonadal maturation varies between raptor species, how the timing of moult relates to the gonadal cycle, whether the timing and degree of sexual maturation varies between juveniles and adults or whether body condition has a significant effect. To address these questions, data on gonadal size and moult for adults and juveniles of both sexes of three raptor species were extracted from the Predatory Bird Monitoring Scheme (based on birds found dead by members of the public). The three species, Sparrowhawk Accipiter nisus, Kestrel Falco tinnunculus and Barn Owl Tyto alba, have different ecologies – diurnal bird predator, diurnal mammal predator and nocturnal mammal predator, respectively. All are single-brooded but have different breeding seasons. The duration of gonadal maturation was markedly different between the species. Barn Owls showed the earliest maturation and the latest gonad regression, and Sparrowhawks the latest maturation and earliest gonad regression. Kestrels were intermediate. In males of all species, the testes remained fully mature throughout their respective breeding seasons. In females, the ovaries remained partially mature throughout the breeding season. Moult started slightly earlier in Sparrowhawks than in Kestrels and coincided with gonadal regression in the two species. Although females of the two species started to moult earlier than males, moult duration was similar between the sexes. Barn Owls showed no distinct annual pattern of moult. In juveniles of all three species, the gonads were smaller than in adults throughout spring and started to mature later. Gonad size in birds that had starved tended to be smaller than in birds dying from other causes, but did not influence the difference in gonad mass between adults and juveniles and between seasons. Body condition had no effect on moult. Whilst ecology has led to the evolution of different breeding seasons, differences between species, and between adults and juveniles, are mediated through adaptive differences in their reproductive physiology.
  Ibis 10/2009; 151(4):654-666. · 2.43 Impact Factor