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Cambridge Immunology Network

 

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 was Professor of Clinical Microbiology at the Cambridge Institute for Therapeutic Immunology and Infectious Diseases from 2018-2025. In 2025 Gupta was elected to The Hong Kong Jockey Club Chair in Global Health at Cambridge University and is co-director of The Global Health Institute in Hong Kong.

At CITIID Gupta leads on communications and outreach and he has been lead of the NIHR BRC Infection Theme since 2023. His work has spans molecular virology and the study of adaptive immunity to viruses such as HIV and SARS-CoV-2. He has led an active program of work in innate immunity for over a decade, particularly on macrophage defences against viruses and the role of cell cycle transitions in regulation of cellular functions.

Gupta has advised the UK government on COVID-19. In 2020 he appeared in the list of 100 most influential people by TIME; in 2022, 2023 and 2024 Gupta featured in the Clarivate list of the world’s most highly cited scientists. He became a fellow of the UK Academy of Medical Sciences in 2021. In 2023 he received the Translational Microbiology prize from the UK Microbiology Society and in 2024 Gupta’s lab team were finalists in the MRC Impact Prize for open science. He was invited to deliver the prestigious JD Bernal Prize Lecture at the University of London in 2024.

Research

The Gupta lab has worked in HIV drug resistance both at molecular and population levels, and his work showing exponential rises in transmitted HIV resistance in Africa through multi-country collaborations alongside WHO (Gupta et al, Lancet 2012, Gupta et al, Lancet Infectious Diseases 2018) led to change in WHO treatment guidelines for HIV, with recommendation for use of integrate inhibitors as first line core drugs. Gupta also reported the problem of tenofovir resistance in low-middle income settings and defined its emergence and characteristics through establishing the TenoRes collaboration with Bob Shafer at Stanford (Gregson et al, Lancet Infectious diseases 2016; Gregson et al, Lancet Infectious diseases 2017). His drug resistance work also revealed the dynamics of virus evolution under non-suppressive protease inhibitor based ART in South Africa (Kemp et al mBio 2022), and revealed novel resistance determinants to protease inhibitors in a study from Nigeria (Datir et al, mBio 2020). Work in South Africa has elucidated determinants of treatment success for integrase inhibitor based therapy (Siedner et al, Nature Communications 2020) and also led to understanding of HIV transmission clustering in rural KZN where HIV seroprevalence is over 30% (Kemp et al, Nature Communications 2024).

In March 2019 the lab reported HIV cure following an 'unrelated' stem cell transplant in the so-called London Patient. This was only the second case of a patient cured of HIV (Gupta et al, Nature 2019, Gupta et al, Lancet HIV 2020). During his time working on HIV reservoirs, the group elucidated why macrophages are infected in vivo by revealing cell cycle transitions in macrophages that radically changed virus susceptibility via SAMHD1 (Mlcochova et al, EMBO J 2016; Meng et al, Cell Reports 2024). The team went on to show that drugs like etoposide and bacterial LPS could arrest macrophages, rendering them HIV resistant (Mlcochova et al, EMBO J 2017, Mlcochova et al, Cell Reports 2019).

During the COVID-19 pandemic, along with SAMBA II inventor Helen Lee, the team brought the first rapid near patient nucleic acid testing to the clinic (Collier et al, Cell Reports Medicine 2020). This work was internationally recognised and the SAMBA II platform is still used at CUH as well as in a large number of other UK institutions. Gupta's group reported the first evidence for immune escape and infectivity enhancement of SARS-CoV-2 within host, driven by convalescent plasma, thus also defining the process by which new variants likely arise in immune compromised individuals (Kemp et al, Nature 2021). This work informed infection control policies for immune compromised hosts. Follow up work has defined the replication advantages of Alpha (Meng et al, Cell Reports 2021) and Delta variants with highly efficient ability to fuse cells (Mlcochova et al, Nature 2021). The latter work was the first demonstration of breakthrough infection following vaccination with an immune evasive variant. Based on data generated by colleagues in India at INSACOG and our analyses, the US CDC changed its guidelines on masking following vaccination, recommending continued use of masks even after vaccine.

The group also reported the tropism shift of the Omicron variant (Meng et al, Nature 2022). These observations have translated to the clinic, reflecting disease severity of Delta versus Omicron and critically aiding public health policy regarding newly emerging variants at global scale. Finally, Gupta’s lab also defined defects in COVID-19 vaccine responses amongst vulnerable individuals such as the elderly (Collier et al, Nature 2021; Ferreira Cell Reports 2023; Sievers et al, NPJ Vaccines 2025) and those with vasculitis (Kamelian et al, Science Advances 2025). 

 

Current work in the lab involves:

  1. Defining immune landscapes and investigating imprinted immunity to COVID-19 across diverse populations: immune compromised, elderly, those in sub Saharan Africa.
  2. Investigation of functional characteristics of the SARS-CoV-2 spike type I glycoprotein: for example we are interested in defining importance of the N terminal domain and furin cleavage site on infectivity and immune evasion. We are extending work into animal CoV that use ACE2 as their entry receptor to investigate how species jumps may be facilitated by mutations in CoV spikes.
  3. Genomic analyses of chronic COVID-19 infection in immune compromised individuals.
  4. Analysis of Mpox vaccine responses in Nigeria amongst individuals with HIV-1 and investigation of possible occult transmission of Mpox in Nigeria.
  5. HIV drug resistance and transmission characteristics in Nigeria and South Africa.
  6. Macrophage cell cycle transitions and their role in innate immune responses/inflammatiom. We are investigating the relationship between cell cycle and the recently described master regulator of myeloid inflammation (ETS2).

 

Our industry partners in the above projects include GSK and AZ and we acknowledge funding from Wellcome, NIH, Lister, Rosetrees and most recently the Hong Kong Jockey Club that has been critical for our work.

 

Publications

Key publications: 

 

SARS CoV-2– lead author works

Kimia Kamelian, Benjamin Sievers, Michael Chen-Xu , Sam Turner, Mark Tsz Kin Cheng, Altaf Mazharul, Steven A. Kemp2, Adam Abdullahi2, Kata Csiba1, Dami A. Collier1,2, Petra Mlcochova2, Bo Meng2, Rachel B. Jones3, The CITIID-NIHR BioResource COVID-19 Collaboration, Derek Smith4, Rainer Doffinger5, Rona M. Smith, Gupta RK

Humoral responses to SARS-CoV-2 vaccine in vasculitis-related immune suppression.

Science Advances 2025; 11 (7) DOI: 10.1126/sciadv.adq3342

 

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, 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.

 

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; Aug; 596:417–422. 

 

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 LL, 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 May;593:136-141

 

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 Apr;592:277-282                  

 

Mlcochova P and Gupta RK. Cyclin D3 restricts SARSCoV 2 Envelope incorporation into virions and interferes with viral spread.

EMBO Journal 2022. 41:e111653

 

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, 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 role in the B.1.1.7 Alpha Variant.

Cell Reports 2021. Jun 29;35(13):109292

 

HIV-1 – lead author works

Kemp SA, Kamelian K, Cuadros DF; PANGEA Consortium; Vukuzazi Team; Cheng MTK, Okango E, Hanekom W, Ndung'u T, Pillay D, Bonsall D, Wong EB, Tanser F, Siedner MJ, Gupta RK. HIV transmission dynamics and population-wide drug resistance in rural South Africa

Nature Communications. 2024 Apr 29;15(1):3644. doi: 10.1038/s41467-024-47254-z

 

Siedner MJ, Moorhouse MA, Simmons B, de Oliveira T, Lessells R, Giandhari J, Kemp SA, Chimukangara B, Akpomiemie G, Serenata CM, Venter WDF, Hill A, Gupta RK. Reduced efficacy of HIV-1 integrase inhibitors in patients with drug resistance mutations in reverse transcriptase.

Nature Communications 2020; 1;11(1):5922.

 

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 AJ, Lever AML, Edwards SG, Gabriel IH, Olavarria E. HIV-1 remission following CCR5Δ32/Δ32 haematopoietic stem-cell transplantation.

Nature 2019; Apr;568(7751):244-248

 

Meng B, Zhao N, Wiet N, Ortmann B, Maxwell P, Nathan J, Gupta RK. Hypoxia drives HIF2-dependent reversible macrophage cell cycle entry.

Cell Reports 2024: DOI:https://doi.org/10.1016/j.celrep.2024.114471

 

Mlcochova P, 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

 

Mlcochova P, Caswell S, Taylor I, Towers GJ, Gupta RK. DNA damage induced by topoisomerase inhibitors activates SAMHD1 and blocks HIV-1 infection of macrophages.

The EMBO J 2018; 37:50–62

 

Mlcochova P, Sutherland KA, Watters SA, Bertoli C, de Bruin RAM, Rehwinkel J, Neil SJ, Lenzi GM, Kim B, Khwaja A, Gage MC, Georgiou C, Chittka A, Yona S, Noursadeghi M, Towers GJ, Gupta RK. A G1– like state allows HIV– 1 to bypass SAMHD1 restriction in macrophages.

The EMBO J 2017; Mar 1;36(5):604-616.

 

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.

The Lancet HIV 2020; Sep;7(9):e620-e628.

 

Gupta RK, Peppa D, Hill AL, Gálvez C, Salgado M, Pace M, McCoy LE, Griffith SA, Thornhill J, Alrubayyi A, Huyveneers LEP, Nastouli E, Grant P, Edwards SG , Innes A, Frater J, Nijhuis M,  Wensing AMJ, Martinez-Picado J, Olavarria E. 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, 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, Inzauke S, 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.

The Lancet Infectious Diseases 2018 Mar;18(3):346-355

 

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.

The Lancet Infectious Diseases 2017;17: 296-304.

 

Gregson J, Tang M, Ndembi N…., Shafer RW, Gupta RK on behalf of the TenoRes study group. Global epidemiology of drug resistance following failure of WHO recommended first line regimens for adult HIV– 1 infection – a multi– centre retrospective cohort study.

The Lancet Infectious Diseases 2016. May;16(5):565– 75

 

Gupta RK, Jordan MR, Sultan BJ, Hill A, Davis DHJ, Gregson J, Sawyer W, Hamers RL, Ndembi N, Pillay D, 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; 380(9849):1250– 8.

 

Contact Details

Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus Puddicombe Way, Cambridge CB2 0AW