Áine McKnight

Title: Professor

MSc, PhD

Professor of Viral Pathology

Centre: Centre for Immunology and Infectious Disease.

Recent and ongoing research projects:

Áine’s group currently focus on novel host cell restriction factors that inhibit HIV replication contemporaneously with reverse transcription and before the virus has the opportunity to integrate its genome into host DNA.

Her group also continues to investigate neutralisation of HIV. In east London she has recruited over 500 patients infected with viruses from all over the world. So far she has shown that the diversity of HIV may not be the major obstacle, once thought, for development of a vaccine because neutralisation is not clade specific. Among this cohort of infected patients we also have a small cohort of viraemic controllers and we are currently investigating if neutralising antibodies could have a role.

Bio

Áine was educated in Dublin, Ireland. Throughout her academic career, she 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 and Robin Weiss). In 2000, she won a fellowship by The Wellcome Trust to develop an independent research group to focus on non-co receptor determinants of HIV replication in cells at The Wohl Virion Centre, University College London. She was subsequently awarded a Medical Research Council (MRC) Senior Non-clinical Fellowship. She moved to Barts & The London Medical School in 2006 to take up a position of Professor of Viral Pathology.

Research

The interests of Áine’s group focus mainly on the interface between HIV and the immune system with regard to adaptive humoral and innate immunity.

She described an innate immune mechanism (Lv-2) that inhibits HIV replication after cellular entry resulting in abortive infection. Her group mapped two viral genes to be involved in overcoming this antiviral effect. One determinant mapped to the viral capsid (CA). This was not unexpected because the restriction factor, TRIM5α, to HIV and SIV, also targets CA. However, surprisingly, a second determinant mapped to the viral envelope protein (Env) which remains on the outside of the cell after fusion. How could it affect events after fusion? To explain this anomaly we showed that a virus with an appropriate Env could sidestep the Lv2 restriction by using an alternative pathway to enter the cell.

Her group showed that the viral ‘trick’ to change entry route to avoid resistance factors may not be confined to Lv2 or to HIV but Murine and Feline retrovirus Envs also have this ability. Her group is currently mapping the host gene(s) involved in Lv2. cDNA cloning failed so she took a ‘broad sweep’ approach applying a high throughput whole genome siRNA screen. AP2 and Dynamin endocytic factors were identified to lead to Lv2. The screen revealed a further 114 factors that inhibit HIV prior to integration.

Publications

Key Publications

Publications last 5 years:

Katherine C. Groves, David F. Bibby, Duncan Clark, Are Isaksen, Jane R. Deayton, Jane Anderson, Chloe Orkin, Andrew J. Stagg, Áine McKnight. Disease Progression in Human Immunodeficiency Virus-1 Infected Viremic Controllers Disease Progression in HIV-1 Controllers. 2012 JAIDS, Accepted 16^th August

Li Liu, Nidia MM Oliveira, Kelly M Cheney, Corinna Pade, Hanna Dreja, Ann-Marie H Bergin, Viola Borgdorff, David H Beach, Cleo L Bishop, Matthias T Dittmar and Áine McKnight. Genome wide screen identifies the PAF1 complex as a surveillance system that inhibits Human Immunodeficiency Virus Type 1 infection. Retrovirology. 2011; 8: 94.

Marlén M. I. Aasa-Chapman, Stéphane Hué , Kelly M. Cheney and Áine McKnight. Evidence in vivo for a Reservoir of HIV-1 Highly Sensitive to Neutralizing Antibodies. 2011, PLoS One.; 6(8).

Ian. P. Harrison and Áine McKnight. Cellular entry via an actin and clathrin dependent route is required for Lv2 restriction of HIV-2. Virology, 2011, 415, 1 (47).

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).

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, 7:81.

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.

Kathryn H Richards, Marlén MI Aasa-Chapman, Áine McKnight, and Paul R Clapham. Modulation of HIV-1 macrophage-tropism among R5 envelopes occurs before detection of neutralizing antibodies. Retrovirology. 2010; 7: 48.

Bridie A Kelly, Ian Harrison, Áine McKnight, and Curtis B Dobson. Anti-infective activity of apolipoprotein domain derived peptides in vitro: identification of novel antimicrobial peptides related to apolipoprotein B with anti-HIV activity. 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 2010 PLoS One 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: 165.

Áine McKnight and Daniel J Pennington. HIV Vaccine Approaches. Encyclopaedia of life Sciences (ELS), John Wiley & Sons, Ltd (June 2009)

Anna Forsman, Els Beirnaert, Marlén Aasa-Chapman, Bart Hoorelbeke Andrea Gorlani, Karolin Hijazi, Willie Koh, Vanessa Tack, Amos Zhao, Agnieszka Szynol, David Lutje Hulsik, Charles Kelly, Áine McKnight, Theo Verrips, Hans de Haard and Robin Weiss. Llama antibody fragments with cross-subtype HIV-1 neutralising properties and high affinity for HIV-1gp120. Journal of Virology 2008;82(24):12069.

Marlén M. I. Aasa-Chapman and Áine McKnight “HIV vaccines a long road ahead” Ibscientific Journal of Science 2007; Vol 2(3), .41.

Bridie A. Kelly, Stuart J. Neil, Áine McKnight, Joana M. Santos, Photini Sinnis, Edward R. Jack, David A. Middleton and Curtis B. Dobson.Apolipoprotein E-derived anti-microbial peptide analogues with altered membrane. FEBS Journal 2007 (17), 4511.

Áine McKnight and Marlén M.I. Aasa-Chapman. Clade specific neutralising vaccines for HIV: An appropriate target? 2007 Current HIV Research, 5(6), 554.

All publications from PubLists

Groves KC, Bibby DF, Clark DA et al. (2012). Disease Progression in Human Immunodeficiency Virus-1 Infected Viremic Controllers.. J Acquir Immune Defic Syndr Vol., () -.
10.1097/QAI.0b013e318269c414

Harrison IP, McKnight A (2011). Cellular entry via an actin and clathrin-dependent route is required for Lv2 restriction of HIV-2.. Virology Vol.415, (1) 47-55.
10.1016/j.virol.2011.04.001

Liu L, Oliveira NM, Cheney KM et al. (2011). A whole genome screen for HIV restriction factors.. Retrovirology Vol.8, () 94-.
10.1186/1742-4690-8-94

Aasa-Chapman MM, Cheney KM, Hué S et al. (2011). In vivo emergence of HIV-1 highly sensitive to neutralizing antibodies.. PLoS One Vol.6, (8) e23961-.
10.1371/journal.pone.0023961

Dreja H, O'Sullivan E, Pade C et al. (2010). Neutralization activity in a geographically diverse East London cohort of human immunodeficiency virus type 1-infected patients: clade C infection results in a stronger and broader humoral immune response than clade B infection.. J Gen Virol Vol.91, (Pt 11) 2794-2803.
10.1099/vir.0.024224-0

Koh WW, Forsman A, Hué S et al. (2010). Novel subtype C human immunodeficiency virus type 1 envelopes cloned directly from plasma: coreceptor usage and neutralization phenotypes.. J Gen Virol Vol.91, (Pt 9) 2374-2380.
10.1099/vir.0.022228-0

Richards KH, Aasa-Chapman MMI, McKnight A et al. (2010). Modulation of HIV-1 macrophage-tropism among R5 envelopes occurs before detection of neutralizing antibodies. RETROVIROLOGY Vol.7, () 1742-4690 -.
10.1186/1742-4690-7-48

Kelly BA, Harrison I, McKnight A et al. (2010). Anti-infective activity of apolipoprotein domain derived peptides in vitro: identification of novel antimicrobial peptides related to apolipoprotein B with anti-HIV activity. BMC IMMUNOL Vol.11, () 1471-2172 -.
10.1186/1471-2172-11-13

Corti D, Langedijk JPM, Hinz A et al. (2010). Analysis of Memory B Cell Responses and Isolation of Novel Monoclonal Antibodies with Neutralizing Breadth from HIV-1-Infected Individuals. PLOS ONE Vol.5, (1) 1932-6203 -.
10.1371/journal.pone.0008805

Oliveira NM, Trikha R, McKnight Á (2010). A novel envelope mediated post entry restriction of murine leukaemia virus in human cells is Ref1/TRIM5? independent.. Retrovirology Vol.7, () 81-.
10.1186/1742-4690-7-81

Cheney KM, McKnight A (2010). Interferon-Alpha Mediates Restriction of Human Immunodeficiency Virus Type-1 Replication in Primary Human Macrophages at an Early Stage of Replication. PLoS One Vol.5, (10) 1932-6203 e13521-.
10.1371/journal.pone.0013521

Doyle T, Garcia-Diaz A, Booth C et al. (2009). High-risk sexual behaviour and HIV-1 superinfection: an indication for early initiation of antiretroviral therapy?. HIV MED Vol.10, () 1464-2662 54-55.

Groves KC, Bibby D, Isaksen A et al. (2009). Altered T cell homeostasis and activation in HIV-1 elite suppressors with low CD4+T-cell counts. RETROVIROLOGY Vol.6, () 1742-4690 -.

Dibben O, Assa-Chapman M, Lewis J et al. (2009). Investigation of the sensitivity of acute-phase HIV-1 isolates to type I interferons. RETROVIROLOGY Vol.6, () 1742-4690 -.

Dreja H, O'Sullivan E, Pade C et al. (2009). Neutralisation activity in a geographically diverse East London cohort of HIV-1 infected patients. RETROVIROLOGY Vol.6, () 1742-4690 -.

Forsman A, Beirnaert E, Aasa-Chapman MM et al. (2008). Llama antibody fragments with cross-subtype human immunodeficiency virus type 1 (HIV-1)-neutralizing properties and high affinity for HIV-1 gp120.. J Virol Vol.82, (24) 12069-12081.
10.1128/JVI.01379-08

McKnight A, Aasa-Chapman MM (2007). Clade specific neutralising vaccines for HIV: an appropriate target?. Curr HIV Res Vol.5, (6) 554-560.

Kelly BA, Neil SJ, McKnight A et al. (2007). Apolipoprotein E-derived antimicrobial peptide analogues with altered membrane affinity and increased potency and breadth of activity. FEBS J Vol.274, (17) 1742-464X 4511-4525.
10.1111/j.1742-4658.2007.05981.x

Aasa-Chapman MM, Seymour CR, Williams I et al. (2006). Novel envelope determinants for CCR3 use by human immunodeficiency virus.. J Virol Vol.80, (21) 0022-538X 10884-10889.
10.1128/JVI.01030-06

Aasa-Chapman MM, Aubin K, Williams I et al. (2006). Primary CCR5 only using HIV-1 isolates does not accurately represent the in vivo replicating quasi-species.. Virology Vol.351, (2) 0042-6822 489-496.
10.1016/j.virol.2006.04.002

Marchant D, Neil SJ, McKnight A (2006). Human immunodeficiency virus types 1 and 2 have different replication kinetics in human primary macrophage culture.. J Gen Virol Vol.87, (Pt 2) 0022-1317 411-418.
10.1099/vir.0.81391-0

Marchant D, Neil SJ, Aubin K et al. (2005). An envelope-determined, pH-independent endocytic route of viral entry determines the susceptibility of human immunodeficiency virus type 1 (HIV-1) and HIV-2 to Lv2 restriction.. J Virol Vol.79, (15) 0022-538X 9410-9418.
10.1128/JVI.79.15.9410-9418.2005

Neil SJ, Aasa-Chapman MM, Clapham PR et al. (2005). The promiscuous CC chemokine receptor D6 is a functional coreceptor for primary isolates of human immunodeficiency virus type 1 (HIV-1) and HIV-2 on astrocytes.. J Virol Vol.79, (15) 0022-538X 9618-9624.
10.1128/JVI.79.15.9618-9624.2005

Neil SJ, McKnight A, Gustafsson K et al. (2005). HIV-1 incorporates ABO histo-blood group antigens that sensitize virions to complement-mediated inactivation.. Blood Vol.105, (12) 0006-4971 4693-4699.
10.1182/blood-2004-11-4267

Aasa-Chapman MM, Holuigue S, Aubin K et al. (2005). Detection of antibody-dependent complement-mediated inactivation of both autologous and heterologous virus in primary human immunodeficiency virus type 1 infection.. J Virol Vol.79, (5) 0022-538X 2823-2830.
10.1128/JVI.79.5.2823-2830.2005

Aasa-Chapman MMI, Hayman A, Newton P et al. (2004). Development of the antibody response in acute HIV-1 infection. AIDS Vol.18, (3) 0269-9370 371-381.
10.1097/01.aids.0000111403.02002.00

Schmitz C, Marchant D, Neil SJ et al. (2004). Lv2, a novel postentry restriction, is mediated by both capsid and envelope.. J Virol Vol.78, (4) 0022-538X 2006-2016.

McKnight A, Weiss RA (2003). Blocking the docking of HIV-1.. Proc Natl Acad Sci U S A Vol.100, (19) 0027-8424 10581-10582.
10.1073/pnas.2035071100

Morner A, Thomas JA, Bjorling E et al. (2003). Productive HIV-2 infection in the brain is restricted to macrophages/microglia. AIDS Vol.17, (10) 0269-9370 1451-1455.
10.1097/01.aids.0000076269.76134.c7

Willey SJ, Reeves JD, Hudson R et al. (2003). Identification of a subset of human immunodeficiency virus type 1 (HIV-1), HIV-2, and simian immunodeficiency virus strains able to exploit an alternative coreceptor on untransformed human brain and lymphoid cells. J VIROL Vol.77, (11) 0022-538X 6138-6152.
10.1128/JVI.77.11.6138-6152.2003

Thomas ER, Shotton C, Weiss RA et al. (2003). CD4-dependent and CD4-independent HIV-2: consequences for neutralization.. AIDS Vol.17, (3) 0269-9370 291-300.
10.1097/01.aids.0000050804.28043.58

Willey S, Roulet V, Reeves JD et al. (2003). Human Leydig cells are productively infected by some HIV-2 and SIV strains but not by HIV-1.. AIDS Vol.17, (2) 0269-9370 183-188.
10.1097/01.aids.0000042968.95433.66

Clapham PR, McKnight A (2002). Cell surface receptors, virus entry and tropism of primate lentiviruses. J GEN VIROL Vol.83, () 0022-1317 1809-1829.
10.1099/vir.0.18313-0

McKnight A, Griffiths DJ, Dittmar M et al. (2001). Characterization of a late entry event in the replication cycle of human immunodeficiency virus type 2.. J Virol Vol.75, (15) 0022-538X 6914-6922.
10.1128/JVI.75.15.6914-6922.2001

Clapham PR, McKnight A (2001). HIV-1 receptors and cell tropism. BRIT MED BULL Vol.58, () 0007-1420 43-59.

Teaching

Topics for PhD supervision:

HIV host cell restriction factors
HIV tropism and neutralization
Innate immunity to viruses

PhD Students:

Current PhD students

Ana Guerrero Alonso

Past PhD students

Elaine Thomas
Sophie Houligue
David Marchant
Nishant Pawa
Katherine Groves (MD)

Contact

Centre for Immunology and Infectious Disease
Blizard Institute
Barts and The London School of Medicine and Dentistry
Blizard Building
4 Newark Street
London E1 2AT

Centre Administrator: Jaya Rajamanie
020 7882 2329
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020 7882 2314

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