Late pupal visual system

George Kassiotis group

Antiviral immunity

Viral infections represent a major challenge to the immune system. Certain viruses cause acute infections in humans, which can be rapidly fatal within days (e.g. 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) and 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 progressive immune deficiency, HIV infection is characterized by generalized immune activation, with lymphadenopathy and accelerated turnover of lymphocytes, both infected and uninfected. The origin of immune activation in HIV infection is unknown, but it is thought to arise from increased microbial exposure due to diminishing immunity. Instead, we showed in a virus-free mouse model that conditional ablation of activated CD4+ T cells, the targets of immunodeficiency viruses, reproduces both HIV-associated immune deficiency and activation, attributable to insufficiency in memory and regulatory CD4+ T cells, respectively. This suggests activated CD4+ T cell killing as a common etiology for both immune deficiency and activation in HIV infection.

Lymphadenopathy (lymph node enlargement) in mice with conditional ablation of activated CD4+ T cells (DTA) in comparison with control wild-type (WT) mice.

Lymphocyte activation (expression of CD44) in non-targeted CD8+ T cells isolated from mice with ablation of activated CD4+ T cells (DTA) or control wild-type (WT) mice.

Selected publications

Kassiotis group

Dr George Kassiotis

George Kassiotis
gkassio@nimr.mrc.ac.uk

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