Research in the Gupta lab focusses on host-pathogen and drug-pathogen interactions to inform HIV treatment and curative strategies.
HIV drug resistance, HIV persistence and cure, cellular biology of macrophages.
Biography
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.
Research
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. His recent work is aimed at cell cycle dependent changes in macrophage biological activity and viral permissivity. 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 has teams in both the UK and at the Africa Health Research Institute in Durban South Africa. Our work focuses on two areas:
Studying HIV drug resistance to protease / integrase inhibitors and implications for global scale up of antiretroviral therapy. Listen to Prof Gupta’s Positively Alive Podcast
Dissecting the biology of macrophage-virus interactions given myeloid cells are parasitised by HIV and are a difficult-to-treat reservoir.
COVID-19 related work
His group has recently introduced the SAMBA II point of care test into clinical practice at Addenbrookes for rapid diagnosis of COVID19. During the pandemic the lab has also started a basic science program to understand the basis of the second immune mediated part of the disease and evolution of the virus within patients in response to convalescent plasma therapy and the antiviral drug remdesevir.
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:
Pfizer vaccine sera activity against B.1.1.7
Prelim Paper – Responses to SARS-CoV-2 following vaccination
The group is also involved in testing novel materials for anti SARS-CoV-2 activity for PPE as part of the 3D MFM collaboration.
COVID-19: What can we learn from the HIV/Aids Pandemic? Guardian Podcast
COVID Six Months On – BBC and Professor Ravi Gupta
Interview with Nature Reviews Microbiology – Detecting COVID-19 at the bedside
Publications
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. In press Nature 2021.
SiednerMJ, 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. In press, Nature Communications 2020
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 in the ‘London Patient’. 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. The EMBO J.; 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. Clin Infect Dis.; 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. Clin Infect Dis.; 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. Clin Infect Dis; 2015 Mar 16. pii: civ219.
Sutherland KA, Ghosn J , Gregson J, Mbisa JL , Chaix ML, Cohen Codar I, Delfraissy JF, Delaugerre C and Gupta RK. HIV-1 subtype influences susceptibility and response to monotherapy with the protease inhibitor lopinavir/ritonavir. Journal of Antimicrobial Chemotherapy; 2015; 70(1):243-8
Mlcochova P, Watters S, Towers GJ, Noursadeghi M, Gupta RK. Vpx complementation of ‘non-macrophage tropic’ R5 viruses reveals robust entry of infectious HIV-1 cores into macrophages. Retrovirology;2014 Mar 21;11:25. doi: 10.1186/1742-4690-11-25
Gupta RK, Goodall RL, Ranopa M, Kityo C, Munderi P, Lyagoba F, Mugarura L, Gilks CF, Kaleebu P, Pillay D; DART Virology Group and Trial Team. High rate of HIV resuppression after viral failure on first-line antiretroviral therapy in the absence of switch to second-line therapy. Clin Infect Dis.; 2014 Apr;58(7):1023-6. doi: 10.1093/cid/cit933.
Sutherland KA, Mbisa JL, Ghosn J, Chaix ML, Cohen Codar I, Hue S, Delfraissy JF, Delaugerre C, Gupta RK. Phenotypic characterization of virologic failure following lopinavir/ritonavir monotherapy using full-length gag-protease genes. Journal of Antimicrobial Chemotherapy; 2014; 69 (12): 3340-3348
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.
Sauter D, Hué S, Petit SJ, PlantierJC, Towers GJ, Kirchhoff K & Gupta RK. HIV-1 Group P is unable to antagonize human tetherin by Vpu, Env or Nef. Retrovirology; 2011; Dec 15;8(1):103.
Gupta RK, Kohli A, McCormick AL, Towers GJ, Pillay D, Parry CM. Full length HIV-1 Gag determines protease inhibitor susceptibility within in vitro assays. AIDS; 2010; July 24(11):1651-1655
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.
