Institute of Immunity and Transplantation


Virus entry & immune evasion

Find out about Dr Joe Grove's research on virus entry and immune evasion.

Antibody evasion by HCV and HIV.

A virus particle is a molecular machine that enters host cells to deliver the viral genome, which in turn hijacks the cell’s biosynthetic machinery to perform viral replication.

Virus entry pathways are defined by interactions with receptors at the cell surface. For instance human immunodeficiency virus (HIV) particles undergo sequential interaction with CD4 and CCR5/CXCR4 to trigger fusion of the viral and host membranes. Whereas hepatitis C virus (HCV) has a more complex entry programme involving at least six receptors.

Neutralising antibodies (nAbs) are produced by the humoral immune system to control and prevent viral infection. nAbs specifically recognise and bind to structural components of virus particles and frustrate entry by, for instance, preventing receptor interactions. However, viruses such as HIV and HCV have evolved an array of countermeasures to evade nAbs. Strategies include antigenic variation, direct cell-to-cell transmission and conformational masking of critical epitopes.

I am using molecular virology, clinically relevant patient samples and cutting edge super-resolution imaging to disset nAb evasion by HIV and HCV with the ultimate goal of finding interventions that overcome viral countermeasures. Super-resolution reconstructions (pictured) display the nanoscale cell-surface organisation of CCR5 and CD81, receptors for HIV and HCV respectively, and HIV-like particles that have been labelled with a neutralising antibody.