CD8 lymphocytes mitigate HIV-1 persistence in lymph node follicular helper T cells during hyperacute-treated infection

Omolara O. Baiyegunhi, Jaclyn Mann, Trevor Khaba, Thandeka Nkosi, Anele Mbatha, Funsho Ogunshola, Caroline Chasara, Nasreen Ismail, Thandekile Ngubane, Ismail Jajbhay, Johan Pansegrouw, Krista L. Dong, Bruce D. Walker, Thumbi Ndung’u and Zaza M. Ndhlovu ()
Additional contact information
Omolara O. Baiyegunhi: Africa Health Research Institute (AHRI)
Jaclyn Mann: The Doris Duke Medical Research Institute, University of KwaZulu-Natal
Trevor Khaba: The Doris Duke Medical Research Institute, University of KwaZulu-Natal
Thandeka Nkosi: Africa Health Research Institute (AHRI)
Anele Mbatha: The Doris Duke Medical Research Institute, University of KwaZulu-Natal
Funsho Ogunshola: Africa Health Research Institute (AHRI)
Caroline Chasara: Africa Health Research Institute (AHRI)
Nasreen Ismail: The Doris Duke Medical Research Institute, University of KwaZulu-Natal
Thandekile Ngubane: The Doris Duke Medical Research Institute, University of KwaZulu-Natal
Ismail Jajbhay: Prince Mshiyeni Memorial Hospital
Johan Pansegrouw: Prince Mshiyeni Memorial Hospital
Krista L. Dong: Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University
Bruce D. Walker: Africa Health Research Institute (AHRI)
Thumbi Ndung’u: Africa Health Research Institute (AHRI)
Zaza M. Ndhlovu: Africa Health Research Institute (AHRI)

Nature Communications, 2022, vol. 13, issue 1, 1-13

Abstract: Abstract HIV persistence in tissue sites despite ART is a major barrier to HIV cure. Detailed studies of HIV-infected cells and immune responses in native lymph node tissue environment is critical for gaining insight into immune mechanisms impacting HIV persistence and clearance in tissue sanctuary sites. We compared HIV persistence and HIV-specific T cell responses in lymph node biopsies obtained from 14 individuals who initiated therapy in Fiebig stages I/II, 5 persons treated in Fiebig stages III-V and 17 late treated individuals who initiated ART in Fiebig VI and beyond. Using multicolor immunofluorescence staining and in situ hybridization, we detect HIV RNA and/or protein in 12 of 14 Fiebig I/II treated persons on suppressive therapy for 1 to 55 months, and in late treated persons with persistent antigens. CXCR3+ T follicular helper cells harbor the greatest amounts of gag mRNA transcripts. Notably, HIV-specific CD8+ T cells responses are associated with lower HIV antigen burden, suggesting that these responses may contribute to HIV suppression in lymph nodes during therapy. These results reveal HIV persistence despite the initiation of ART in hyperacute infection and highlight the contribution of virus-specific responses to HIV suppression in tissue sanctuaries during suppressive ART.

Date: 2022
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DOI: 10.1038/s41467-022-31692-8

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