HIV-specific T-cell responses reflect substantive in vivo interactions with infected cells despite long-term therapy
HIV-specific T-cell responses reflect substantive in vivo interactions with infected cells despite long-term therapy
Abstract Antiretroviral therapies (ART) durably suppress HIV replication to undetectable levels – however, infection persists in the form of long-lived reservoirs of infected cells with integrated proviruses, that re-seed systemic replication if ART is interrupted. A central tenet of our current understanding of this persistence is that infected cells are shielded from immune recognition and elimination through a lack of antigen expression from proviruses. Efforts to cure HIV infection have therefore focused on reactivating latent proviruses to enable immune-mediated clearance, but these have yet to succeed in driving reductions in viral reservoirs. Here, we revisited the question of whether HIV reservoirs are predominately immunologically silent from a new angle, by querying the dynamics of HIV-specific T-cell responses over long-term ART for evidence of ongoing recognition of HIV-infected cells. We show that T-cell responses to autologous reservoir viruses persist over years, and that the maintenance of HIV-Nef-specific responses was uniquely associated with residual frequencies of infected cells. These responses disproportionately exhibited a cytotoxic, effector functional profile, indicative of recent in vivo recognition of HIV-infected cells. These results indicate substantial visibility of the HIV reservoir to T-cells on stable ART, presenting both opportunities and challenges for the development of therapeutic approaches to curing HIV infection.
Gramatica Andrea、Stevenson Eva M.、Ward Adam R.、Truong Ronald、Thomas Allison S.、Bui John K.、Gandhi Rajesh T.、McMahon Deborah K.、Bosch Ronald J.、Macatangay Bernard、Cyktor Joshua C.、Eron Joseph J.、Jones R. Brad、Lalama Christina M.、Mellors John W.、Danesh Ali、Dilling Thomas R.、for the ACTG A5321 Team、Huang Szu-Han、Terry Sandra、Alberto Winiffer D. Conce、Mota Talia M.、Lee Guinevere Q.、Khadka Pragya
Division of Infectious Diseases, Weill Cornell MedicineDivision of Infectious Diseases, Weill Cornell MedicineDivision of Infectious Diseases, Weill Cornell Medicine||Department of Microbiology, Immunology, and Tropical Medicine, George Washington University||PhD Program in Epidemiology, George Washington UniversityDepartment of Microbiology, Immunology, and Tropical Medicine, George Washington UniversityDepartment of Microbiology, Boston University School of MedicineDivision of Infectious Diseases, Weill Cornell MedicineDivision of Infectious Diseases, Massachusetts General HospitalDepartment of Medicine, University of Pittsburgh School of MedicineCenter for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public HealthDepartment of Medicine, University of Pittsburgh School of MedicineDepartment of Medicine, University of Pittsburgh School of MedicineDepartment of Medicine, University of North Carolina at Chapel HillDivision of Infectious Diseases, Weill Cornell Medicine||Department of Microbiology, Immunology, and Tropical Medicine, George Washington UniversityCenter for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public HealthDepartment of Medicine, University of Pittsburgh School of MedicineDivision of Infectious Diseases, Weill Cornell MedicineDivision of Infectious Diseases, Weill Cornell MedicineDivision of Infectious Diseases, Weill Cornell Medicine||Department of Microbiology, Immunology, and Tropical Medicine, George Washington UniversityDivision of Infectious Diseases, Weill Cornell MedicineDivision of Infectious Diseases, Weill Cornell MedicineDivision of Infectious Diseases, Weill Cornell MedicineDivision of Infectious Diseases, Weill Cornell MedicineDivision of Infectious Diseases, Weill Cornell Medicine
医药卫生理论医学研究方法基础医学
Gramatica Andrea,Stevenson Eva M.,Ward Adam R.,Truong Ronald,Thomas Allison S.,Bui John K.,Gandhi Rajesh T.,McMahon Deborah K.,Bosch Ronald J.,Macatangay Bernard,Cyktor Joshua C.,Eron Joseph J.,Jones R. Brad,Lalama Christina M.,Mellors John W.,Danesh Ali,Dilling Thomas R.,for the ACTG A5321 Team,Huang Szu-Han,Terry Sandra,Alberto Winiffer D. Conce,Mota Talia M.,Lee Guinevere Q.,Khadka Pragya.HIV-specific T-cell responses reflect substantive in vivo interactions with infected cells despite long-term therapy[EB/OL].(2025-03-28)[2025-06-19].https://www.biorxiv.org/content/10.1101/2020.08.28.272625.点此复制
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