Cambridge Institute of Therapeutic Immunology & Infectious DiseaseThe 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 , and in 2021 he was elected to Fellowship of the Academy of Medical Sciences UK
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.
Media
HIV Drug Resistance – commissioned by WHO to give a holistic perspective on the threat of resistant HIV infection
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
People who changed the world – Professor Ravi Gupta
Publications
Below are key publications from the Gupta lab.
Ferreira IATM, Lee CYC, Foster WS, Abdullahi A, Dratva LM, Tuong ZK, Stewart BJ, Ferdinand JR, Guillaume SM, Potts MOP, Perera M, Krishna BA, Peñalver A, Cabantous M, Kemp SA, Ceron-Gutierrez L, Ebrahimi S; CITIID-NIHR BioResource COVID-19 Collaboration; Lyons P, Smith KGC, Bradley J, Collier DA, McCoy LE, van der Klaauw A, Thaventhiran JED, Farooqi IS, Teichmann SA, MacAry PA, Doffinger R, Wills MR, Linterman MA, Clatworthy MR, Gupta RK. Atypical B cells and impaired SARS-CoV-2 neutralization following heterologous vaccination in the elderly. Cell Reports. 2023 Aug 16;42(8):112991. doi: 10.1016/j.celrep.2023.112991
Abdullahi A, Oladele D, Owusu M, Kemp SA, Ayorinde J, Salako A, Fink D, Sylverken A, Ige F, Onwuamah C, Boadu KO, Osuolale Q, Frimpong JO, Abubakar R, Okuruawe A, Liboro G, Agyemang LD, Ayisi-Boateng N, Odubela O, Ohihoin G, Ezechi O, Kamasah J, Ameyaw E, Arthur J, Kyei D, Owusu D, Usman O, Mogaji S, Dada A, Agyei G, Ebrahimi S, Gutierrez LC, Aliyu S, Rainer Doffinger R, Audu R, Adegbola R, Mlcochova P, Phillips R, Solako BL and Gupta RK. SARS-CoV-2 Antibody Responses to AZD1222 Vaccination in West Africa, Nature Communications 2022. https://www.nature.com/articles/s41467-022-33792-x
Meng B, Datir R, Choi J; CITIID-NIHR Bioresource COVID-19 Collaboration, Bradley JR, Smith KGC, Lee JH, Gupta RK. SARS-CoV-2 spike N-terminal domain modulates TMPRSS2-dependent viral entry and fusogenicity. Cell Reports. 2022 Aug 16;40(7):111220. doi: 10.1016/j.celrep.2022.111220.
Meng B, Abdullahi A, Ferreira IATM, Goonawardane N, Saito A, Kimura I, Yamasoba D, Gerber PP, Fatihi S, Rathore S, Zepeda SK, Papa G, Kemp SA, Ikeda T, Toyoda M, Tan TS, Kuramochi J, Mitsunaga S, Ueno T, Shirakawa K, Takaori-Kondo A, Brevini T, Mallery DL, Charles OJ; CITIID-NIHR BioResource COVID- Collaboration; Genotype to Phenotype Japan (GP-Japan) Consortium members; Ecuador-COVID19 Consortium, Bowen JE, Joshi A, Walls AC, Jackson L, Martin D, Smith KGC, Bradley J, Briggs JAG, Choi J, Madissoon E, Meyer K, Mlcochova P, Ceron-Gutierrez L, Doffinger R, Teichmann SA, Fisher AJ, Pizzuto MS, de Marco A, Corti D, Hosmillo M, Lee JH, James LC, Thukral L, Veesler D, Sigal A, Sampaziotis F, Goodfellow IG, Matheson NJ, Sato K, Gupta RK. Altered TMPRSS2 usage by SARS-CoV-2 Omicron impacts tropism and fusogenicity. Nature. 2022 Feb 1. doi: 10.1038/s41586-022-04474-x.
Mlcochova P, Kemp S, Dhar MS, Papa G, Meng B, Ferreira IATM, Datir R, Collier DA, Albecka A, Singh S, Pandey R, Brown J, Zhou J, Goonawardane N, Mishra S, Whittaker C, Mellan T, Marwal R, Datta M, Sengupta S, Ponnusamy K, Radhakrishnan VS, Abdullahi A, Charles O, Chattopadhyay P, Devi P, Caputo D, Peacock T, Wattal DC, Goel N, Satwik A, Vaishya R, Agarwal M; Indian SARS-CoV-2 Genomics Consortium (INSACOG); Genotype to Phenotype Japan (G2P-Japan) Consortium; CITIID-NIHR BioResource COVID-19 Collaboration, Mavousian A, Lee JH, Bassi J, Silacci-Fegni C, Saliba C, Pinto D, Irie T, Yoshida I, Hamilton WL, Sato K, Bhatt S, Flaxman S, James LC, Corti D, Piccoli L, Barclay WS, Rakshit P, Agrawal A, Gupta RK. SARS-CoV-2 B.1.617.2 Delta variant replication, sensitivity to neutralising antibodies and vaccine breakthrough. Nature 2021 Sep 6. doi: 10.1038/s41586-021-03944-y. Online ahead of print.
Collier DA, Ferreira IATM, Kotagiri P, Datir R, Lim E, Touizer E, Meng B, Abdullahi A; CITIID-NIHR BioResource COVID-19 Collaboration, Elmer A, Kingston N, Graves B, Le Gresley E, Caputo D, Bergamaschi L, Smith KGC, Bradley JR, Ceron-Gutierrez L, Cortes-Acevedo P, Barcenas-Morales G, Linterman MA, McCoy L, Davis C, Thomson E, Lyons PA, McKinney E, Doffinger R, Wills M, Gupta RK. Age-related immune response heterogeneity to SARS-CoV-2 vaccine BNT162b2. Nature. 2021 Jun 30. doi: 10.1038/s41586-021-03739-1. Online ahead of print. https://www.nature.com/articles/s41586-021-03739-1
Meng B, Kemp SA, Papa G, Datir R, Ferriera IATM, Harvey WT, Lytras S, Mohamed A, Gallo G, Thakur N, Collier DA, Mlcochova P, Marelli S, The COVID-19 Genomics UK (COG-UK) Consortium, Matheson NJ, Carabelli A, Kenyon JC , Lever AM, De Marco A, Saliba C, Katja C, Cameroni E, Piccoli L, Corti C, James LC, Robertson DL, Bailey D, Gupta RK. Recurrent emergence of SARS-CoV-2 spike deletion H69/V70 and its role in the B.1.1.7 lineage. In press Cell Reports 2021 https://doi.org/10.1016/j.celrep.2021.109292
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.
