Professor Áine McKnight, BSc, MSc, PhDProfessor of Viral PathologyCentre: Genomics and Child HealthEmail: a.mcknight@qmul.ac.ukTelephone: 020 7882 2314Room Number: OE-08Website: https://www.researchgate.net/profile/Aine_McKnightProfileTeachingResearchPublicationsSupervisionProfileÁine 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 neutralising 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 Bart’s & The London medical school in 2006 to take up a position of Professor of Viral Pathology. LinkedIn: /aine-mcknight-4147357aTeaching Qualifications Professor Áine McKnight Educational Fellowship 2019Higher Education Academy of Queen Mary University of LondonAcademic Development, Education, and the Promotion of Teaching (ADEPT) Taught Courses Bachelor of Science, BSc BMD323 Bachelor of Medicine, Bachelor of Surgery (Medicinae Baccalaureus, Baccalaureus Chirurgiae; MMBS) MBBS - Undergraduate Medicine, Fundamentals of Medicine MBBS - Undergraduate Medicine Year 3 Infection, Immunity and Genetics MBBS - Graduate Entry Programme Year 2 Infection, Immunity and Genetics Master of Science, MSc MSc Medical Microbiology MSc Clinical Microbiology Áine loves virology and loves teaching it. Students enter the wonderful world of viruses with introductory lectures that take them on bespoke virological journeys (Bachelor of Medicine, Bachelor of Surgery (MBBS year 1), Bachelor of Science (BSc) and Master of Science (MSc). As a student you will learn where viruses fit in the rest of the living universe. How many types are there? How big are they in relation to the rest of life on earth? Viruses cannot be seen by the naked eye or even ordinary light microscopes. How then, were they first discovered? They are composed of relatively tiny codes of either DNA or RNA. Left on a bench they do nothing. Are they even alive? You will learn how all viruses, RNA or DNA reach the same endpoint of memory RNA (mRNA) generation to direct protein production to make new viruses. You will learn how virus structures are exquisitely adapted with optimum ability to traverse the cytoplasm and gain access to the nucleus and how the viral capsid structure is optimal for assembly- no energy required! How do such miniscule entities wreak such catastrophic plagues across the globe such as the Covid-19 pandemic? Learn how viruses influenced the outcome of wars and perhaps even the world cup 2022! There are many ways that viruses are transmitted; respiratory viruses in droplets propelled by sneezes and coughs; by aerosols that can travel further in the air once generated by singing or shouting; by direct touch person-to-person or animal to person and vice versa (zoonosis). Some viruses can’t survive outside the body for long and are transmitted by blood and sex, for example HIV. Other viruses are transferred from host to host by insects (vector borne transmission). Imagine the evolution and adaptation required for a virus to circumnavigate two such different hosts! Once they reach their host you will learn how viruses enter their target cells and make millions or billions of copies of themselves and spread through the body in preparation for release and further rounds of transmission and infection. You will learn how different viruses cause different diseases. Now enter the world of epidemiology where we track the devastation caused during outbreaks using maths such as R numbers and herd immunity. Most importantly, how do we prevent viruses from infecting? For those students taking more advanced courses (MBBS year 3, Bachelor of Science year 3 (BSc) and Master of Science (MSc) you will learn greater particulars of virus classification including the Baltimore classification system. How classification systems can help you to generate the life cycle of any virus found on earth (so far!). You will understand the molecular details of families of viruses such as Retroviridae, Coronaviridae and many other respiratory viruses. You will learn the details of how they cause disease and why some became pandemic while others did not. What we know about emerging viruses will be explored. Can we ever be able to predict emerging viruses or should we just rely on surveillance? You will learn how viruses spill over from animals to humans through zoonosis and potentially lead to worldwide pandemics. You will consider whether cells or viruses came first in evolution. You will gain an in-depth understanding of the nuances involved in studying the origin of viruses. It's difficult! Unlike animal and plant fossils most viruses do not leave relics enabling us to chart their evolution. The exception is the family of endogenous retroviruses (ERVs). Retroviruses are unique: they integrate their genomes into the host cell’s DNA. When they integrate their genomes into the germ cell DNA they are inherited through the germline in a mendelian fashion. Sequencing genomes reveals pandemics that have lasted 15 million years! Indeed almost 8% of our DNA consists of ERVs. Compare that to only 2% of our DNA coding for proteins! We are more virus than human! Learn how such ‘foreign’ virus DNAs have been ‘put to work’ by our own cells. But retroviruses are a lot of trouble too. You will learn about their central role and the role of other viruses in inducing cancer. Studying viruses has led us to understanding the mechanism of carcinogenesis in general. You will probe if the inducing virus needs to be continuously present or replicating in cells for the cancer to continue to thrive. This is easy to rationalise for retroviruses which integrate their genomes and are replicated along with the cell. When viruses other than Retroviruses induce cancer so do these viruses infect cells and cause cancer in a ‘hit and run’ fashion? Or are there other mechanisms at play. Finally, you will learn in detail how antivirals and vaccines are designed. First you need to know their life cycle! ResearchResearch Interests:The interests of Áine’s group (Dr Joseph Gibbons, Dr Corinna Pade and Mr. Maximillian Biguet) focus mainly on the interface between viruses and the immune system with regard to adaptive humoral and innate (intrinsic) immunity. Her current focus is on intrinsic immunity and mechanism of action of proteins constitutively expressed in cells that restrict viral infection. She described an innate immune mechanism, lentiviral restriction-2 (Lv2), which inhibits HIV replication after cellular entry resulting in abortive infection. Using a whole genome siRNA screening approach she has identified over 100 proteins involved in intrinsic resistance to HIV infection of cells including, RNA associated Anti-viral Factor (REAF), which is responsible for Lv2 (Lui et al., Marno et al. 2014). Determinants of sensitivity or resistance to REAF reside in the capsid or envelope proteins (Schmitz et al, Marno et al 2017). REAF associates with reverse transcription complexes (Marno et al 2014) which results in the abortion of reverse transcription. It is upregulated in macrophages in response to reverse transcription and HIV induces its degradation counteracting its activity at the viral reverse transcription stage using the virally encoded Vpr protein. In 2019 Áine’s research focus re-directed to the SARS-CoV-2 pandemic. Prompt action by the Medical College of St Bartholomew's Hospital Trust, the Rosetrees Trust and the John Black Charitable foundation to fund Áine’s research enabled her group to develop capability to COVID-19 research. Quickly they were in a position to respond to new waves of variants including Wuhan (D614), alpha, beta, gamma, delta, omicron and so on. In London in March 2020, with colleagues at Bart’s NHS (James Moon, Charlotte Manisty and Thomas Treibel) and UCL (Maddy Noursadeghi) she assembled a consortium of 731 health care workers to study the longitudinal responses to infection against SARS-CoV-2. Thus, we captured a snapshot of participants’ immune status prior to becoming infected and subsequent responses that occurred weekly for four weeks and then monthly for two years. We included cross-sectional longitudinal studies across three dose vaccination. The group examined neutralisation of SARS-CoV-2 and variants regarding their sensitivity, potency, immunogenicity and susceptibility to immune responses induced by natural infection or vaccination or both (Boyton, Altman groups Imperial College London). They determined immunity generated by prior infection with ‘common cold’ coronaviruses (Maini UCL). Also they collaborated in the development of a quantitative, multiplexed, targeted proteomics method for ascertaining variant specific SARS-CoV-2 antibodies (Heywood and Mills). Additionally with UCL (Noursadeghi) they showed that IFI27 transcripts could be a biomarker for early phase SARS-CoV-2 infection useful for screening individuals at high risk of infection. With Upkar Gill and Patrick Kennedy, (QMUL School of Medicine and Dentistry, Blizard institute), they discovered a signaling pathway in cells associated with the production of IgG in COVID-19. With Riddell, Cutino-Moguel and team in the Royal London they studied three patients with HIV-1 and chronic SARS-CoV-2 infection with evidence of selection and persistence of mutations associated with increased transmissibility and neutralisation escape. Áine’s 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. Research Group Joseph Gibbons PublicationsKey Publications Immune boosting by B.1.1.529 (Omicron) depends on previous SARS-CoV-2 exposure.Catherine J. Reynolds†, Corinna Pade†, Joseph M. Gibbons†, Ashley D. Otter†, Kai-Min Lin, Diana Muñoz Sandoval, Franziska P. Pieper, David K. Butler, Siyi Liu, George Joy, Nasim Forooghi, Thomas A. Treibel, Charlotte Manisty, James C. Moon, Amanda Semper, Tim Brooks, Áine McKnight‡, Daniel M. Altmann‡, Rosemary J. Boyton‡. Science (2022) 377. Generation of novel SARS-CoV-2 variants on B.1.1.7 lineage in three patients with advanced HIV disease.Anna Riddell, Beatrix Kele, Kathryn Harris, Jon Bible, Maurice Murphy, Subathira Dakshina, NathaniStorey, Dola Owoyemi, Corinna Pade, Joseph M. Gibbons, David Harrington, Eliza Alexander, Áine McKnight, Teresa Cutino-Moguel. Clin Infect Dis. (2022) 409. Evaluating the efficacy and safety of a novel prophylactic nasal spray in the prevention of SARS-CoV-2 infection: A multi-centre, double blind, placebo-controlled, randomised trial.Damian Balmforth, James A Swales, Laurence Silpa, Alan Dunton, Kay E. Davies, Stephen G. Davies, Archana Kamath, Jayanti Gupta, Sandeep Gupta, M.Abid Masood, Áine McKnight, Doug Rees, Angela J. Russell, Manu Jaggi, Rakesh Uppal. Journal of Clinical Virology (2022) 105248. Discordant neutralizing antibody and T cell responses in asymptomatic and mild SARS-CoV-2 infection.Catherine J. Reynolds, Swadling, L., Gibbons, J. M., Pade, C [truncated], Jensen, M. P., McKnight Á§., Boyton, R§. J. Science Immunology, (2020) 5. HIV-1 Accessory Protein Vpr Interacts with REAF/RPRD2 To Mitigate Its Antiviral Activity.Gibbons, J. M., Marno, K. M., Pike, R., Lee, W. J., Jones, C. E., Ogunkolade, B. W., Pardieu, C., Bryan, A., Fu, R. M., Warnes, G., Rowley, P. A., Sloan, R. D., & Áine McKnight. Journal of Virology, (2019) 94. All PublicationsSupervisionThe PAF1 complex is composed of the proteins Paf1, Ctr9, Cdc73, Rtf1, and Leo1 and associates with RNA polymerase I and II. Mr. Maximillian Biguet is studying the role of the PAF-1 complex in the restriction of HIV infection in collaboration with Dr Miguel Branco (QMUL, Faculty of Medicine and Dentistry, Blizard Institute).