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Author Notes:

Corresponding Author. Francois Villinger, New Iberia Research Center, 4401 W Admiral Doyle Drive, New Iberia, LA 70560, Ph. 337 482 0225, Fax: 337 373 0075

Jung Joo Hong was responsible for the concept and design of the study, performing experiments analyzing the data and writing the manuscript.

Praveen K Amancha, Siddappa N Byrareddy, Eduardo L Silveira, and Sanjeev Gumber performed experiments and analyzed the data.

Aftab A Ansari and Kyu-Tae Chang provided scientific input and assisted in manuscript revision.

Francois Villinger was responsible for the concept and design of the study and in revising the manuscript.

The authors would like to thank the staff and veterinarians of the Yerkes National Primate Research Center for their excellent care of the animals, Dr. Gelezunias (Gilead) for the gift of PMPA and FTC, Dr. Hazuda (Merck) for the provision of integrase inhibitor and the NIH ARRRP for the provision of the KK59 Mab.

Subjects:

Research Funding:

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:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Immunology
  • Infectious Diseases
  • Virology
  • antiretroviral drugs
  • germinal center
  • follicular helper T cell
  • SIMIAN IMMUNODEFICIENCY VIRUS
  • T FOLLICULAR HELPER
  • ANTIBODY-MEDIATED REJECTION
  • HIV-1 REPLICATION
  • CELL DEPLETION
  • IN-VIVO
  • RESPONSES
  • THERAPY
  • VIREMIA
  • MACAQUES

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

Tools:

Journal Title:

AIDS

Volume:

Volume 31, Number 13

Publisher:

, Pages 1819-1824

Type of Work:

Article | Post-print: After Peer Review

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.

Copyright information:

© 2017 Wolters Kluwer Health, Inc. All rights reserved.

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