George Kassiotis

Retroviral Immunology

Infectious diseases cause a quarter of all deaths worldwide and one in five cancers. Certain viruses cause acute infections in humans, which can be rapidly fatal within days, for example influenza A and smallpox viruses. In contrast, other viruses are able to persist chronically in infected individuals, despite induction of an immune reaction (e.g. HIV, hepatitis and herpes viruses). Almost all humans are chronically infected by one or more persistent viruses. Our understanding of the pathogenic processes of viral infection remains incomplete.

In addition to facing a multiplicity of infection with exogenous viruses, all mammals, including humans, have a long-standing symbiotic relationship with a considerable number of microbial species, such as the microbiota and endogenous retroviruses (ERVs).

Recent evidence suggests that ERVs and other transposable elements actively shape gene transcriptional networks, responsible for cell identity. These networks can be responsive to environmental factors, exemplified by the response of immune cells to infection. Correspondingly, ERV activity is also responsive to external factors, providing a potential link with disease development.

Figure 1

Figure 1. Heatmap of ERV expression induced by either the nucleoside analogue BrdU or the bacterial constituent LPS in murine dendritic ce.

Figure 2

Figure 2. Numerous retroviral particles (pseudocoloured) in the extracellular spaces of a lymphoma resected from a lymphocyte-deficient Rag1-/-mouse. (Click to view larger image)

Selected publications

Donnarumma T, Young GR, Merkenschlager J, Eksmond U, Bongard N, Nutt SL, Boyer C, Dittmer U, Le-Trilling VT, Trilling M, Bayer W, Kassiotis G. (2016)
Opposing Development of Cytotoxic and Follicular Helper CD4 T Cells Controlled by the TCF-1-Bcl6 Nexus.
Cell Rep 17,1571-1583. PubMed abstract

Mavrommatis B, Baudino L, Levy P, Merkenschlager J, Eksmond U, Donnarumma T, Young G, Stoye J, Kassiotis G. (2016)
Dichotomy between T Cell and B Cell Tolerance to Neonatal Retroviral Infection Permits T Cell Therapy.
J Immunol 197(9),3628-3638. PubMed abstract

Merkenschlager J, Ploquin MJ, Eksmond U, Andargachew R, Thorborn G, Filby A, Pepper M, Evavold B, Kassiotis G. (2016)
Stepwise B-cell-dependent expansion of T helper clonotypes diversifies the T-cell response.
Nat Commun 7,10281. PubMed abstract

Young, G.R., Eksmond, U., Salcedo, R., Alexopoulou, L., Stoye, J.P. and Kassiotis, G. (2012)
Resurrection of endogenous retroviruses in antibody-deficient mice.
Nature 49, 774-778. PubMed abstract

Young, G.R., Ploquin, M.J., Eksmond, U., Wadwa, M., Stoye, J.P. and Kassiotis, G. (2012)
Negative selection by an endogenous retrovirus promotes a higher-avidity CD4 T cell response to retroviral infection.
PLoS Pathogens 8(5), e1002709. PubMed abstract

Marques R, Williams A, Eksmond U, Wullaert A, Killeen N, Pasparakis M, Kioussis D, Kassiotis G. (2009)
Generalized immune activation as a direct result of activated CD4 T cell killing.
J Biol  8(10),93. PubMed abstract

Antunes I, Tolaini M, Kissenpfennig A, Iwashiro M, Kuribayashi K, Malissen B, Hasenkrug K, Kassiotis G. (2008)
Retrovirus-specificity of regulatory T cells is neither present nor required in preventing retrovirus-induced bone marrow immune pathology.
Immunity 29(5),782-794. PubMed abstract

George Kassiotis

george.kassiotis@crick.ac.uk
+44 (0)20 379 61483

  • Qualifications and history
  • 2000 PhD in Immunology, Hellenic Pasteur Institute, Athens, Greece
  • 2000 Post-doctoral Fellow, Medical Research Council National Institute for Medical Research (MRC NIMR), London, UK
  • 2005 Programme Leader Track, MRC NIMR, London, UK
  • 2011 Programme Leader, MRC NIMR, London, UK
  • 2015 Group Leader, the Francis Crick Institute, London, UK