Completed Infection & Immunity Genetics & Molecular Biology

Cellular immunity and genetic restriction of Influenza, Hepatitis C virus infection and Hepatitis B associated heptocellular carcinoma.

In plain English

AI plain-English summary

T cells—the immune system’s frontline soldiers—often fail to control viruses like influenza and hepatitis C, or to stop hepatitis B from triggering liver cancer, because scientists do not fully understand what makes those T cells effective or ineffective. This matters because the quality of a T cell response determines whether an infection is cleared, becomes chronic, or even harms the host. The same confusion surrounds a protein called IFITM3, which blocks at least 15 RNA viruses—including influenza A and HIV—but whose mechanism of action remains unknown. A common genetic variant in IFITM3 disables this block, yet why this happens is also a mystery. If this research succeeds, it could reveal how to deliberately strengthen T cell responses against specific viruses and cancers, and how to restore or mimic IFITM3’s antiviral activity. That could lead to new treatments for chronic hepatitis B, influenza, and hepatitis C, and potentially for liver cancer—without relying on broad-spectrum drugs that viruses easily evade. The work is fundamentally curiosity-driven: it aims to solve basic puzzles about how our immune system and a key antiviral protein actually work. Past discoveries about T cell biology and restriction factors have already yielded vaccines and antiviral therapies; deeper understanding here could open similar doors.

View original technical description
Human infections, cancer development and the course of disease are mainly influenced by T cell responses. While a robust and appropriate T cell response is beneficial to the host, a weak or inappropriate response can be ineffective or even have a detrimental effect. Numerous factors influence the quality of the T cell response to viral infections or cancer development, predominant among them being the microenvironment of the infection site, the type of cells affected and in the case of infection, the variability of the virus. By understanding the key factors required for efficient control by the T cell response in a number of different viral infections and viral associated cancers, in particular HBV associated HCC, we aim to identify targets to augment and control the immune response as a way of improving the outcome of in several important human diseases. While my group's main focus is T cell responses, a subset of the group focus on the important anti-viral restriction factor IFITM3, which is known to restrict >15 RNA viruses including Influenza A virus, HIV and Hepatitis C virus, however the mechanism of restriction is still unknown. Little conclusive data on IFITM3 is published due to its high homology to other IFITM family members. A single nucleotide polymorphism (SNP) within IFITM3 is known to prevent its viral restriction but again the mechanism for this is unknown. This interesting protein leaves us with several unanswered questions and we aim to characterise this protein using novel reagents in order to elucidate the mechanism by which viral restriction occurs.

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Researchers

Tao Dong (Principal Investigator)

Related Research

Grants with similar aims, by meaning.

Characterisation of host virus interactions.
Innate immune responses to human hepatotropic viral infections
Human antigen-specific T cell responses in viral control and immunopathology
MRC amed - interferon stimulated defences that target hepatitis b virus (hbv) and hepatitis d virus (hdv)
Identification of interferon-stimulated antiviral genes that contribute to the HIV-1 transmission bottleneck

Original classification

Intramural

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