HIV-specific T-cell responses reflect substantive in vivo interactions with infected cells despite long-term therapy

التفاصيل البيبلوغرافية
العنوان: HIV-specific T-cell responses reflect substantive in vivo interactions with infected cells despite long-term therapy
المؤلفون: Sandra Terry, Deborah McMahon, Thomas R. Dilling, Ali Danesh, Szu-Han Huang, Joshua C. Cyktor, Andrea Gramatica, Allison S. Thomas, Christina M. Lalama, R. Brad Jones, Pragya Khadka, Joseph J. Eron, John K. Bui, Eva M. Stevenson, Bernard J.C. Macatangay, Ronald Truong, Winiffer D. Conce Alberto, Guinevere Q. Lee, Talia M. Mota, Ronald J. Bosch, Rajesh T. Gandhi, Adam R. Ward, John W. Mellors
بيانات النشر: Cold Spring Harbor Laboratory, 2020.
سنة النشر: 2020
مصطلحات موضوعية: Immune recognition, medicine.anatomical_structure, Antigen, Effector, In vivo, T cell, Immunology, Human immunodeficiency virus (HIV), medicine, Cytotoxic T cell, Long term therapy, Biology, medicine.disease_cause
الوصف: 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.
DOI: 10.1101/2020.08.28.272625
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_________::6687ccd2f6faf95cb439b20990a1f426
https://doi.org/10.1101/2020.08.28.272625
Rights: OPEN
رقم الانضمام: edsair.doi...........6687ccd2f6faf95cb439b20990a1f426
قاعدة البيانات: OpenAIRE
الوصف
DOI:10.1101/2020.08.28.272625