The role of innate APOBEC3G and adaptive AID immune responses in HLA-HIV/SIV immunized SHIV infected macaques

Yufei Wang, Trevor Whittall, Durdana Rahman, Evelien M Bunnik, Robert Vaughan, Jørgen Schøller, Lesley A. Bergmeier, David Montefiori, Mahavir Singh, Hanneke Schuitemaker, Thomas Lehner

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

The AID/APOBEC family (activation induced deaminase/apolipoprotein B mRNA editing cytokine deaminase) in B cells play important roles in adaptive and innate immunity. Whereas APOBEC3G has been studied in CD4+ T cells and myeloid cells its functional potential in B cells has received little attention. AID combines two critical functions of antibodies, class switching and affinity maturation and may serve as a functional surrogate of protection. These functions were studied following systemic immunization of rhesus macaques with recombinant HLA constructs, linked with HIV and SIV antigens and HSP70 to dextran. The results showed significant upregulation of AID in CD20+ B cells, APOBEC 3G in CD27+ memory B cells and CD4+ effector memory T cells. After immunization the upregulated APOBEC 3G and AID were directly correlated in B cells (p<0.0001). Following challenge with SHIV SF162.P4 the viral load was inversely correlated with AID in B cells and APOBEC 3G in B and T cells, suggesting that both deaminases may have protective functions. Investigation of major interactions between DC, T cells and B cells showed significant increase in membrane associated IL-15 in DC and CD40L in CD4+ T cells. IL-15 binds the IL-15 receptor complex in CD4+ T and B cells, which may reactivate the DC, T and B cell interactions. The overall results are consistent with AID inhibiting pre-entry SHIV by eliciting IgG and IgA antibodies, whereas APOBEC 3G may contribute to the post-entry control of SHIV replication and cellular spread.

Original languageEnglish (US)
Article numbere34433
JournalPLoS One
Volume7
Issue number4
DOIs
StatePublished - Apr 13 2012
Externally publishedYes

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Macaca
Adaptive Immunity
B-lymphocytes
B-Lymphocytes
Cells
HIV
T-cells
T-lymphocytes
T-Lymphocytes
Immunization
Interleukin-15
Interleukin-15 Receptors
immunization
HIV Antigens
Immunoglobulin Class Switching
B-Lymphocyte Subsets
adaptive immunity
Data storage equipment
CD40 Ligand
Antibody Affinity

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

The role of innate APOBEC3G and adaptive AID immune responses in HLA-HIV/SIV immunized SHIV infected macaques. / Wang, Yufei; Whittall, Trevor; Rahman, Durdana; Bunnik, Evelien M; Vaughan, Robert; Schøller, Jørgen; Bergmeier, Lesley A.; Montefiori, David; Singh, Mahavir; Schuitemaker, Hanneke; Lehner, Thomas.

In: PLoS One, Vol. 7, No. 4, e34433, 13.04.2012.

Research output: Contribution to journalArticle

Wang, Y, Whittall, T, Rahman, D, Bunnik, EM, Vaughan, R, Schøller, J, Bergmeier, LA, Montefiori, D, Singh, M, Schuitemaker, H & Lehner, T 2012, 'The role of innate APOBEC3G and adaptive AID immune responses in HLA-HIV/SIV immunized SHIV infected macaques', PLoS One, vol. 7, no. 4, e34433. https://doi.org/10.1371/journal.pone.0034433
Wang, Yufei ; Whittall, Trevor ; Rahman, Durdana ; Bunnik, Evelien M ; Vaughan, Robert ; Schøller, Jørgen ; Bergmeier, Lesley A. ; Montefiori, David ; Singh, Mahavir ; Schuitemaker, Hanneke ; Lehner, Thomas. / The role of innate APOBEC3G and adaptive AID immune responses in HLA-HIV/SIV immunized SHIV infected macaques. In: PLoS One. 2012 ; Vol. 7, No. 4.
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