Early initiation of antiretroviral treatment postSIV infection does not resolve lymphoid tissue activation

• Type of Material: Article
• Authors: Jung Joo Hong, Korea Research Institute of Bioscience & Biotechnology; Eduardo L V Silveira, University of São Paulo; Praveen K Amancha, University of Louisiana Lafayette; Siddappa N. Byrareddy, Emory University; Sanjeev Gumber, Emory University; Kyu-Tae Chang, Korea Research Institute of Bioscience & Biotechnology; Aftab A Ansari, Emory University; Francois Villinger, Emory University
• Language: English
• Date: 2017-08-24
• Publisher: Lippincott, Williams & Wilkins
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2017 Wolters Kluwer Health, Inc. All rights reserved.
• Final Published Version (URL): http://dx.doi.org/10.1097/QAD.0000000000001576
• Title of Journal or Parent Work: AIDS
• ISSN: 0269-9370
• Volume: 31
• Issue: 13
• Start Page: 1819
• End Page: 1824
• Grant/Funding Information: This work was supported in part by NIH grants R01 AI078775 and 8R24OD010947 to F Villinger, NIH grant R01 AI098628 to AA Ansari, NIH OD-51OD11132 to the Yerkes NPRC.
• Keywords: RESPONSES; IN-VIVO; VIREMIA; follicular helper T cell; MACAQUES; CELL DEPLETION; ANTIBODY-MEDIATED REJECTION; Life Sciences & Biomedicine; Science & Technology; HIV-1 REPLICATION; T FOLLICULAR HELPER; germinal center; SIMIAN IMMUNODEFICIENCY VIRUS; Infectious Diseases; THERAPY; Virology; Immunology; antiretroviral drugs
• Research Categories: Health Sciences, Pathology; Health Sciences, Pharmacology

Abstract

Objective: Germinal center resident follicular helper T (TFH) cells in lymphoid follicles are a potential sanctuary for HIV/simian immunodeficiency virus (SIV) replication. But the dynamics of germinal centers upon early initiation of antiretroviral therapy (ART) and their potential role in the formation of viral sanctuaries post-SIV infection are not fully understood. Design: Sequential lymph node biopsies (n = 10) were collected from SIVmac239-infected rhesus macaques before infection, at 5 weeks postinfection/pre-ART, 6 and 12 weeks following ART initiation. These tissues and cells were analyzed for frequencies of TFH cells and assignment of germinal center scores. Results: Modest but significant increases in TFH cells and hyperplastic follicles with large germinal centers were noted during the acute phase of SIV infection (week 5/pre-ART). However, 6 weeks after ART initiation, substantial increases in germinal center TFH cells, germinal center B cells, hyperplastic follicles with large germinal centers, and abundant local IL-21 production were observed, whereas levels of SIV RNA and DNA of lymph nodes had decreased to barely detectable values along with barely detectable levels of SIV antibody-producing cells. An additional 6 weeks of ART did not appreciably decrease germinal center TFH or germinal center scores. Conclusion: Thus, although early ART rapidly controls SIV replication, it does not regulate early lymphoid activation, which may contribute to the seeding and magnitude of viral reservoirs.