Relative efficacy of T cell stimuli as inducers of productive HIV-1 replication in latently infected CD4 lymphocytes from patients on suppressive cART.

Virology
Nadejda Beliakova-BethellCelsa A Spina

Abstract

Quantification of cell-associated replication-competent HIV, in blood samples from patients with undetectable plasma viremia, requires specialized culture conditions that include exogenous pan T cell stimulation. Different research groups have used several stimuli for this purpose; however, the relative efficacies of these T cell stimuli to induce productive HIV replication from latently infected cells ex vivo have not been systematically evaluated. To this end, we compared four commonly used T cell stimuli: 1) irradiated allogeneic cells plus phytohaemagglutinin (PHA); 2) PHA alone; 3) phorbol myristate acetate plus Ionomycin; and 4) immobilized αCD3 plus αCD28 antibodies. End-point dilutions of patient CD4 T cells were performed, using virion RNA production to quantify HIV induction. Our results demonstrated that these activation approaches were not equivalent and that antibody cross-linking of CD3 and CD28 membrane receptors was the most effective means to activate HIV replication from a resting cell state, closely followed by stimulation with irradiated allogeneic cells plus PHA.

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Citations

Apr 13, 2019·PLoS Computational Biology·Daniel I S RosenbloomUNKNOWN Reservoir Assay Validation and Evaluation Network (RAVEN) Study Group
Jun 5, 2019·Pharmaceutics·Nejat Düzgüneş, Krystyna Konopka
Apr 15, 2020·Open Forum Infectious Diseases·Caroline C GarlissJoel N Blankson
Jul 22, 2020·Proceedings of the National Academy of Sciences of the United States of America·Francesco R SimonettiJanet D Siliciano
Nov 26, 2019·Cell Host & Microbe·Jason M HatayeRichard A Koup
Jun 18, 2021·Journal of Virus Eradication·P Nathan EnickMichele D Sobolewski

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