B cell follicle sanctuary permits persistent productive simian immunodeficiency virus infection in elite controllers

Yoshinori Fukazawa, Richard Lum, Afam Okoye, Haesun Park, Kenta Matsuda, Jin Young Bae, Shoko I. Hagen, Rebecca Shoemaker, Claire Deleage, Carissa Lucero, David Morcock, Tonya Swanson, Alfred W. Legasse, Michael Axthelm, Joseph Hesselgesser, Romas Geleziunas, Vanessa M. Hirsch, Paul T. Edlefsen, Michael Piatak, Jacob Estes & 2 others Jeffrey D. Lifson, Louis Picker

Research output: Contribution to journalArticle

230 Citations (Scopus)

Abstract

Chronic-phase HIV and simian immunodeficiency virus (SIV) replication is reduced by as much as 10,000-fold in elite controllers (ECs) compared with typical progressors (TPs), but sufficient viral replication persists in EC tissues to allow viral sequence evolution and induce excess immune activation. Here we show that productive SIV infection in rhesus monkey ECs, but not TPs, is markedly restricted to CD4 + follicular helper T (T FH) cells, suggesting that these EC monkeys' highly effective SIV-specific CD8 + T cells can effectively clear productive SIV infection from extrafollicular sites, but their relative exclusion from B cell follicles prevents their elimination of productively infected T FH cells. CD8 + lymphocyte depletion in EC monkeys resulted in a dramatic re-distribution of productive SIV infection to non-T FH cells, with restriction of productive infection to T FH cells resuming upon CD8 + T cell recovery. Thus, B cell follicles constitute 'sanctuaries' for persistent SIV replication in the presence of potent anti-viral CD8 + T cell responses, potentially complicating efforts to cure HIV infection with therapeutic vaccination or T cell immunotherapy.

Original languageEnglish (US)
Pages (from-to)132-139
Number of pages8
JournalNature Medicine
Volume21
Issue number2
DOIs
StatePublished - 2015

Fingerprint

Simian Immunodeficiency Virus
Virus Diseases
Viruses
B-Lymphocytes
T-cells
Cells
Controllers
T-Lymphocytes
Virus Replication
Haplorhini
Lymphocyte Depletion
Lymphocytes
Macaca mulatta
Immunotherapy
HIV Infections
Vaccination
Chemical activation
HIV
Tissue
Recovery

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

B cell follicle sanctuary permits persistent productive simian immunodeficiency virus infection in elite controllers. / Fukazawa, Yoshinori; Lum, Richard; Okoye, Afam; Park, Haesun; Matsuda, Kenta; Bae, Jin Young; Hagen, Shoko I.; Shoemaker, Rebecca; Deleage, Claire; Lucero, Carissa; Morcock, David; Swanson, Tonya; Legasse, Alfred W.; Axthelm, Michael; Hesselgesser, Joseph; Geleziunas, Romas; Hirsch, Vanessa M.; Edlefsen, Paul T.; Piatak, Michael; Estes, Jacob; Lifson, Jeffrey D.; Picker, Louis.

In: Nature Medicine, Vol. 21, No. 2, 2015, p. 132-139.

Research output: Contribution to journalArticle

Fukazawa, Y, Lum, R, Okoye, A, Park, H, Matsuda, K, Bae, JY, Hagen, SI, Shoemaker, R, Deleage, C, Lucero, C, Morcock, D, Swanson, T, Legasse, AW, Axthelm, M, Hesselgesser, J, Geleziunas, R, Hirsch, VM, Edlefsen, PT, Piatak, M, Estes, J, Lifson, JD & Picker, L 2015, 'B cell follicle sanctuary permits persistent productive simian immunodeficiency virus infection in elite controllers', Nature Medicine, vol. 21, no. 2, pp. 132-139. https://doi.org/10.1038/nm.3781
Fukazawa, Yoshinori ; Lum, Richard ; Okoye, Afam ; Park, Haesun ; Matsuda, Kenta ; Bae, Jin Young ; Hagen, Shoko I. ; Shoemaker, Rebecca ; Deleage, Claire ; Lucero, Carissa ; Morcock, David ; Swanson, Tonya ; Legasse, Alfred W. ; Axthelm, Michael ; Hesselgesser, Joseph ; Geleziunas, Romas ; Hirsch, Vanessa M. ; Edlefsen, Paul T. ; Piatak, Michael ; Estes, Jacob ; Lifson, Jeffrey D. ; Picker, Louis. / B cell follicle sanctuary permits persistent productive simian immunodeficiency virus infection in elite controllers. In: Nature Medicine. 2015 ; Vol. 21, No. 2. pp. 132-139.
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abstract = "Chronic-phase HIV and simian immunodeficiency virus (SIV) replication is reduced by as much as 10,000-fold in elite controllers (ECs) compared with typical progressors (TPs), but sufficient viral replication persists in EC tissues to allow viral sequence evolution and induce excess immune activation. Here we show that productive SIV infection in rhesus monkey ECs, but not TPs, is markedly restricted to CD4 + follicular helper T (T FH) cells, suggesting that these EC monkeys' highly effective SIV-specific CD8 + T cells can effectively clear productive SIV infection from extrafollicular sites, but their relative exclusion from B cell follicles prevents their elimination of productively infected T FH cells. CD8 + lymphocyte depletion in EC monkeys resulted in a dramatic re-distribution of productive SIV infection to non-T FH cells, with restriction of productive infection to T FH cells resuming upon CD8 + T cell recovery. Thus, B cell follicles constitute 'sanctuaries' for persistent SIV replication in the presence of potent anti-viral CD8 + T cell responses, potentially complicating efforts to cure HIV infection with therapeutic vaccination or T cell immunotherapy.",
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