The mechanisms used by viruses to invade and replicate in cells are of fundamental interest, both in terms of improved understanding of infection and pathogenesis, with implications for health and economic wellbeing, but also because viruses are extraordinary tools for revealing how cells work.
We focus on understanding how membrane-containing enveloped viruses interact with cellular membrane systems, how these interactions facilitate or restrict the transmission of viruses from cell to cell and how they impact on viral pathogenesis. We are exploiting our current knowhow to develop knowledge-based interventions against viral infections and/or pathogenesis.
Recently, we have concentrated on HIV, and the closely related simian immunodeficiency viruses (SIV), with a view to understanding fundamental aspects of virus replication in macrophages and how highly conserved trafficking signals in the envelope glycoprotein of SIV impact on pathogenesis.
In new programs of work, we will investigate (1) how interferon-induced transmembrane (IFITM) proteins inhibit the entry of a broad range of enveloped viruses, (2) the potential to develop broad-spectrum antivirals that inhibit the entry of viruses that exploit the same endocytic entry mechanisms, and (3) the cell biological processes underlying virus particle formation.
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Lawrence S, et al (2022). A cellular trafficking signal in the SIV envelope protein cytoplasmic domain is strongly selected for in pathogenic infection. PLoS Pathogens 18:e1010507. doi: 10.1371/journal.ppat.1010507.
Yuan Y, et al (2021). Single-molecule super-resolution imaging of T-cell plasma membrane CD4 redistribution upon HIV-1 binding. Viruses; 13:142 https://doi.org/10.3390/v13010142
Bednarska J, et al (2020). Assembly and release of single HIV VLPs by high-speed correlative SICM. Proc. Natl. Acad. Sci. USA; https://doi.org/10.1073/pnas.2008156117
Pereira P, et al (2020). Super-Beacons: Open-source probes with spontaneous tuneable blinking compatible with live-cell super-resolution microscopy. Traffic; 21:375-385. doi: 10.1111/tra.12728
Giese S, et al (2020). The Nef protein of HIV1 strain AD8 counteracts human Bst2/tetherin. Viruses 12: 459; doi: 10.3390/v1204045