Home| Professor of Viral Pathology |
Contact details:
| Tel: | +44 20 7882 2314 |
| Fax: | +44 20 7882 2181 |
| Email: | a.mcknight@qmul.ac.uk |
| Address: | Centre for Immunology and Infectious Disease, |
Biography:
Throughout her academic career, Prof McKnight has been interested in HIV/AIDS. In 1987, she joined the team of Robin Weiss at the Institute of Cancer Research, London, to study the role of neutralizing antibodies to HIV-1 and HIV-2 in pathogenesis. She was awarded MSc in Immunology in 1990 by King's College, London, and a PhD in 1996 by University of London (supervised by Paul Clapham). In 2000, she won a fellowship (RCDF) by The Wellcome Trust to develop an independent research group to focus on non-coreceptor determinants of HIV replication in cells at The Wohl Virion Centre, University College London. She is currently a Medical Research Council (MRC) Senior Non-clinical Fellow (awarded in 2005).
Research Activity
he interests of my group focus mainly on the interface between HIV and the immune system with regard to humoral immunity and a novel innate immune mechanism described by us (Lv-2) that inhibits HIV replication after cellular entry resulting in abortive infection. We mapped two viral genes to be involved in overcoming this antiviral effect. We are currently mapping the host gene(s) involved. With regard to humoral immunity to HIV-1 infection my group mainly focuses on the role of neutralizing antibodies in controlling HIV-1 and 2 replication. We have shown that activation of the classical complement pathway by serum antibodies can be implicated in the control of primary HIV-1 viremia. More recently we have shown that in acute infection viruses develop with envelopes that are highly sensitive to serum antibody mediated neutralization but eventually these viruses are replaced in the blood by ones that escape serum neutralizing antibodies.
We also have strong interests in HIV tropism and co-receptor use. HIV infects mainly T-cells and macrophages through the use of CD4 and co-receptors usually either CCR5 or CXCR4 chemokine receptors. Recently we have shown that viral Envs amplifed directly from the plasma almost always additionally use a related chemokine receptor CCR3 just as efficiently as CCR5.
Key Publications:
• K.M. Cheney, Á. McKnight. Interferon-Alpha Mediates Restriction of Human Immunodeficiency Virus Type-1 Replication in Primary Human Macrophages at an Early Post-Entry Stage of Replication. PLoS One. 2010 5(10): e13521. doi: 10.1371
• Nidia MM Oliveira, Roochi Trikha and Áine McKnight. A novel envelope mediated post entry restriction of Murine Leukaemia Virus in human cells is Ref1/TRIM5alpha independent. Retrovirology 2010, 7:81doi:10.1186/1742-4690-7-81
• Hanna Dreja, Eithne M. O'Sullivan, Corinna Pade, Kelli M. Greene, Hongmei Gao, Keith Aubin, James Hand, Are Isaksen, Carl D'Souza, Werner Leber, David Montefiori, Michael S. Seaman, Jane Anderson, Chloe Orkin and Áine McKnight. Neutralisation activity in a geographically diverse East London cohort of HIV-1 infected patients: Clade C infection results in a stronger and broader humoral immune response than clade B infection. J General Virology 2010: 91:2794
• Modulation of HIV-1 macrophage-tropism among R5 envelopes occurs before detection of neutralizing antibodies. Kathryn H Richards, Marlén MI Aasa-Chapman, Áine McKnight, and Paul R Clapham. Retrovirology. 2010; 7: 48.
• Anti-infective activity of apolipoprotein domain derived peptides in vitro: identification of novel antimicrobial peptides related to apolipoprotein B with anti-HIV activity. Bridie A Kelly, Ian Harrison, Áine McKnight, and Curtis B Dobson. BMC Immunol. 2010; 11: 13
• Willie W. L. Koh, Anna Forsman, Stephane Hue, Gisela J. van der Velden, David L. Yirrell, Áine McKnight, Robin A. Weiss and Marlen M. I. Aasa-Chapman. Novel subtype C HIV-1 envelopes cloned directly from plasma: Coreceptor usage and neutralisation phenotypes. J General Virology 2010; 91:2374
• Davide Corti, Hans Landedijk, Andreas Hinz, Mike S. Seaman, Fabrizia Vanzetta, Blanca Fernandez, Chiara Silacci, David Jarrossay, Sunita Balla-Jhagjhoorsingh, Hanna Dreja, Eithne O’Sullivan, Corinna Pade, Chloe Orkin, Betty Willems, Debora Pinna, Simon A. Jeffs, John R. Mascola, David C. Montefiori, Wouter Janssens, Winfried Weissenhorn, Áine McKnight, Federica Sallusto, Robin A. Weiss and Antonio Lanzavecchia. Analysis of Memory B Cell Responses and Isolation of Novel Monoclonal Antibodies with Neutralizing Breadth from HIV-1-Infected Individuals PLoS One 2010 5(1)
• K.M. Cheney, Á. McKnight. HIV-2 Tropism and Disease. Lentiviruses and Macrophages: Molecular and Cellular Interactions. M. Desport, Caister Academic Press. 2010: p165-180
