The Gupta lab has worked extensively in HIV drug resistance, both at molecular and population levels, and contributed to the appreciation of the scale of drug resistance globally. The group’s work extends to studies on HIV reservoirs in cells, particularly macrophages. This understanding is relevant to both anatomical compartments where HIV virus replication occurs in macrophages, as well as design of strategies to cure HIV. The Gupta lab works between the UK and the Africa Health Research Institute in Durban South Africa. Listen to Prof Gupta’s Positively Alive Podcast.
Having completed his medical undergraduate studies at Cambridge and Oxford Universities, Ravi Gupta pursued a Masters in Public Health at Harvard as a Fulbright scholar. Upon return he trained in infectious diseases in Oxford and London (UCLH, Hospital for Tropical Diseases) and completed his PhD at UCL on Lentiviral evasion of antiretrovirals and innate immune responses. He established his research group at UCL in 2011 working on genetics and biology of HIV resistance and reservoirs and as promoted to full professor in 2016. Ravi Gupta has been Professor of Clinical Microbiology at the Cambridge Institute for Therapeutic Immunology and Infectious Diseases since 2019. In 2020 he was named as one of the 100 Most influential people by TIME.
COVID-19 related work
In Spring 2020 the team validated and introduced the SAMBA II point of care test into clinical practice at Addenbrookes for rapid diagnosis of COVID-19. During the latter half of 2020 the lab started to study evolution of the virus within patients in response to antibody based therapies, as a paradigm of how new variants with multiple mutations have arisen. The team is also characterising the virology of key spike protein mutations in new variants and their impact on natural and vaccine induced immunity.
Ravi Gupta is a co-opted member of NERVTAG. The New and Emerging Respiratory Virus Threats Advisory Group (NERVTAG) advises the government on the threat posed by new and emerging respiratory viruses.
Please see below for pre-prints:
COVID-19: What can we learn from the HIV/Aids Pandemic? Guardian Podcast
Below are key publications from the Gupta lab.
Collier DA, De Marco A, Ferreira IATM, Meng B, Datir R, Walls AC, Kemp S SA, Bassi J, Pinto D, Fregni CS, Bianchi S, Tortorici MA, Bowen J, Culap K, Jaconi S, Cameroni E, Snell G, Pizzuto MS, Pellanda AF, Garzoni C, Riva A, Elmer A, Kingston N, Graves B, McCoy LE, Smith KG, Bradley JR, Temperton N, Ceron-Gutierrez L L, Barcenas-Morales G, Harvey W, Virgin HW, Lanzavecchia A, Piccoli L, Doffinger R, Wills M, Veesler D, Corti D, Gupta RK. Sensitivity of SARS-CoV-2 B.1.1.7 to mRNA vaccine-elicited antibodies. Nature 2021 DOI: https://www.nature.com/articles/s41586-021-03412-7
Kemp SA, Collier DA, Datir R, Ferreira I, Gayed S, Jahun A, Hosmillo M, Rees-Spear C, Mlcochova P, Lumb IU, Roberts DJ, Chandra A, Temperton N, Sharrocks K, Blane E, Briggs J, van Gils MJ, Smith K, Bradley JR, Smith C, Doffinger R, Ceron-Gutierrez L, Barcenas-Morales G, Pollock DD, Goldstein RA, Smielewska A, Skittrall JP, Gouliouris T, Goodfellow IG, Gkrania-Klotsas E, Illingworth C, McCoy LE, Gupta RK. SARS-CoV-2 evolution during treatment of chronic infection. Nature 2021. https://www.nature.com/articles/s41586-021-03412-7
Siedner MJ, MoorhouseMA, SimmonsB, deOliveiraT, LessellsR, GiandhariJ, KempSA, ChimukangaraB, AkpomiemieG, SerenataCM, VenterWDF, HillA, Gupta RK. Reduced efficacy of HIV-1 integrase inhibitors in patients with drug resistance mutations in reverse transcriptase. Nature Communications 2020 11:5922 https://www.nature.com/articles/s41467-020-19801-x
Collier DA, Assennato SM, Warne B, Sithole N, Sharrocks K, Ritchie A, Ravji P, Routledge M, Sparkes D, Skittrall J, Smielewska A, Ramsey I, Goel N, Curran M, Enoch D, Tassell R, Lineham M, Vaghela D, Leong C, Mok HP, Bradley J, Smith KGC, Mendoza V, Demiris N, Besser M, Dougan G, Lehner PJ, Siedner MJ, Zhang H, Waddington CS, Lee H, Gupta RK; CITIID-NIHR COVID BioResource Collaboration. Point of Care Nucleic Acid Testing for SARS-CoV-2 in Hospitalized Patients: A Clinical Validation Trial and Implementation Study. Cell Reports Medicine; 2020; Jul 15:100062. doi: 10.1016/j.xcrm.2020.100062
Mlcochova P, Collier D, Ritchie A, Assennato SM, Hosmillo M, Goel N, Meng B, Chatterjee K, Mendoza V, Temperton N, Kiss L, James LC, Ciazynska KA, Xiong X, Briggs JA, Nathan JA, Mescia F, Bergamaschi L, Zhang H, Barmpounakis P, Demeris N, Skells R, Lyons PA, Bradley J, Baker S, Allain JP, Smith KG, Bousfield R, Wilson M, Sparkes D, Amoroso G, Gkrania-Klotsas E, Hardwick S, Boyle A, Goodfellow I, Gupta RK; CITIID-NIHR COVID BioResource Collaboration. Combined point of care nucleic acid and antibody testing for SARS-CoV-2 following emergence of D614G Spike Variant. Cell Reports Medicine; 2020 Sep 1:100099. doi:10.1016/j.xcrm.2020.100099
Datir RP, Kemp S, El Bouzidi K, Mlcochova P, Goldstein RA, Breuer J, Towers GJ, Jolly C, Quinones-Mateu ME, Dakum PS, Ndembi N, Gupta RK. In Vivo Emergence of a Novel Protease Inhibitor Resistance Signature in HIV-1 Matrix. In press, MBio; 2020
Gupta-Wright A, Fielding K, van Oosterhout J, Alufandika M, Grint D, Chimbayo E, Heaney J; Byott M, Nastouli E; Mwandumba H, Corbett E, Gupta RK. Virological failure, HIV-1 drug resistance and early mortality in adults admitted to hospital in Malawi: a nested observational cohort study. In press, The Lancet HIV; 2020
MlcochovaP, Winstone H, Zuliani-Alvarez L, Gupta RK.TLR4-Mediated Pathway Triggers Interferon-Independent G0 Arrest and Antiviral SAMHD1 Activity in Macrophages. Cell Reports; 2020; 30 (12), 3972-3980
Gupta RK, Dimitra Peppa, Alison L Hill Cristina Gálvez Maria Salgado5Matthew Pace, Laura E McCoySarah A Griffith, John Thornhill, Aljawharah Alrubayyi, Laura EP Huyveneers, Eleni Nastouli, Paul Grant, Simon G Edwards S , Andrew J Innes, John Frater, Monique Nijhuis, Anne Marie J, Wensing Prof Martinez-Picado J, Eduardo Olavarria. Evidence for HIV-1 Cure After CCR5Δ32/Δ32 Allogeneic Haemopoietic Stem-Cell Transplantation 30 Months Post Analytical Treatment Interruption. The Lancet HIV; 2020; S2352-3018(20)30069-2.
Gupta RK, Abdul-Jawad S, McCoy LE, Mok HP, Peppa D, Salgado M, Martinez-Picado J, Nijhuis M, Wensing AMJ, Lee H, Grant P, Nastouli E, Lambert J, Pace M, Salasc F, Monit C, Innes A, Muir L, Waters L, Frater J, Lever AML, Edwards SG, Gabriel IH, Olavarria E. HIV-1 remission following CCR5Δ32/Δ32 haematopoietic stem-cell transplantation. Nature; 2019 Mar 5. doi: 10.1038/s41586-019-1027-4. [Epub ahead of print]
MlcochovaP, Caswell S, Taylor I, TowersGJ, Gupta RK. DNA damage induced by topoisomerase inhibitors activates SAMHD1 and blocks HIV-1 infection of macrophages. EMBO Journal.; 2018; 37:50–62
Gupta RK, Gregson J, Parkin N, Haile-Selassie H, Tanuri A, Andrade Forero L, Kaleebu P , Watera C, Aghokeng A, Mutenda N, Dzangare J, Hone S, Hang ZZ, Garcia J, Garcia Z, Marchorro P, Beteta E, Roman M, Giron A, Hamers R, InzaukeS, Frenkel LM, Chung MH,de Oliveira T, Pillay D, Naidoo K, Kharsany A, Kugathasan R, Cutino T, Hunt G, Avila Rios S, Doherty M, Jordan MR, Bertagnolio S. HIV-1 drug resistance prior to initiation or re-initiation of first-line antiretroviral therapy in low- and middle-income countries – a meta regression analysis. Lancet Infectious Diseases; 2018 Mar;18(3):346-355
Collier DA, Iwuji C, Derache A, de Oliveira T, Okesola N, Calmy A, Dabis F, Pillay D, Gupta RK for the ANRS 12249 TasP Study Group. Virological Outcomes of second– line protease inhibitor based treatment for HIV– 1 in a high prevalence rural South African setting – a competing risk prospective cohort analysis. Clinical Infectious Diseases.; 2017 Apr 15;64(8):1006-1016
Petra Mlcochova, Katherine A Sutherland, Sarah A Watters, Cosetta Bertoli, Rob AM de Bruin, Jan Rehwinkel, Stuart J Neil, Gina M Lenzi, Baek Kim, Asim Khwaja, Matthew C Gage, Christiana Georgiou, Alexandra Chittka, Simon Yona, Mahdad Noursadeghi, Greg J Towers, Gupta RK. A G1‐like state allows HIV‐1 to bypass SAMHD1 restriction in macrophages. EMBO Journal; 2017; e201696025. Published online 25.01.2017
Kugathasan R, Collier DA, Haddow LJ, El Bouzidi K, Edwards SG, Cartledge JD, Miller RF, Gupta RK. Diffuse white matter signal abnormalities on MRI are associated with HIV-1 viral escape in the central nervous system among patients with neurological symptoms. Clinical Infectious Diseases.; 2017 Apr 15;64(8):1059-106
Gregson J, Kaleebu P, Marconi VC, van Vuuren C, Ndembi N, Hamers RL, Kanki P, Hoffmann CJ, Lockman S, Pillay D, de Oliveira T, Clumeck N, Hunt G, Kerschberger B, Shafer RW, Yang C, Raizes E, Kantor R, Gupta RK. Occult drug resistance to thymidine analogues and multidrug resistant HIV-1 following failure of first line tenofovir-based antiretroviral regimens in sub Saharan Africa: a retrospective multi-centre cohort study. Lancet Infect Dis; 2016, Volume 17, No. 3, p296–304, March 2017
TenoRes Study Group (*senior author). Global epidemiology of drug resistance following failure of WHO recommended first line regimens for adult HIV-1 infection – a multi-centre retrospective cohort study. Lancet Infect Dis; May 2016; Volume 16, No. 5, p565–575
Smith NMG, Mlcochova P, Watters SA, Aasa-Chapman, Rabin N, Moore S, Edwards SG, Garson JA, Grant PR, Ferns RB, Kashuba A, Mayor NP, Schellekens J, Marsh SGE, McMichael AJ, Perelson AS, Pillay D, Goonetilleke N, Gupta RK. Proof-of-principle for immune control of global HIV-1 reactivation in vivo. Clinical Infectious Diseases; 2015 Mar 16. pii: civ219.
Gupta RK, Sultan BJ, Hill A, Davis DHJ, Gregson J, Sawyer W, Hamers RL, Ndembi N, Pillay D, Jordan MR & Bertagnolio S. Global trends in antiretroviral resistance in untreated HIV-1 infected individuals following ART roll-out in resource-limited settings: a global collaborative study and meta-regression analysis. The Lancet;2012. Oct 6;380(9849):1250-8.
Gupta RK, Mlcochova P, Pelchen-Matthews A, Petit SJ, Mattiuzzo G, Pillay D, Takeuchi Y, Marsh M, Towers GJ. Simian Immunodeficiency Virus envelope glycoprotein counteracts tetherin/BST-2/CD317 by intracellular sequestration. Proceedings of the National Academy of Sciences; USA 2009; Dec8; 106:20889-20894
Gupta RK, Hué S, Schaller T, Verschoor E, Pillay D and Towers GJ. Mutation of a single residue renders human tetherin resistant to HIV-1 Vpu-mediated depletion. PLoS Pathogens; 2009 May;5(5):e1000443.
Gupta RK, Hill A, Sawyer W, Cozzi-Lepri A, von Wyl V, Yerly S, Dias Lima V, Gunthard HF, Gilks C, Pillay D. Virological monitoring and resistance to first-line highly active antiretroviral therapy in adults infected with HIV-1 treated under WHO guidelines: a systematic review and meta-analysis. Lancet Infectious Diseases;2009;9(7):409-17.