Possible clearance of transfusion-acquired nef/LTR-deleted attenuated HIV-1 infection by an elite controller with CCR5 Δ32 heterozygous and HLA-B57 genotype.

Abstract

BACKGROUND:

Subject C135 is one of the members of the Sydney Blood Bank Cohort, infected in 1981 through transfusion with attenuated nef/3' long terminal repeat (LTR)-deleted HIV-1, and has maintained undetectable plasma viral load and steady CD4 cell count, in the absence of therapy. Uniquely, C135 combines five factors separately associated with control of viraemia: nef/LTR-deleted HIV-1, HLA-B57, HLA-DR13, heterozygous CCR5 Δ32 genotype and vigorous p24-stimulated peripheral blood mononuclear cell (PBMC) proliferation. Therefore, we studied in detail viral burden and immunological responses in this individual.

METHODS:

PBMC and gut and lymph node biopsy samples were analysed for proviral HIV-1 DNA by real-time and nested PCRs, and nef/LTR alleles by nested PCR. HIV-specific antibodies were studied by Western blotting, and CD4+ and CD8+ T lymphocyte responses were measured by proliferation and cytokine production in vitro.

RESULTS:

PBMC samples from 1996, but not since, showed amplification of nef alleles with gross deletions. Infectious HIV-1 was never recovered. Proviral HIV-1 DNA was not detected in recent PBMC or gut or lymph node biopsy samples. C135 has a consistently weak antibody response and a substantial CD4+ T cell proliferative response to a previously described HLA-DR13-restricted epitope of HIV-1 p24 in vitro, which augmented a CD8+ T cell response to an immunodominant HLA-B57-restricted epitope of p24, while his T cells show reduced levels of CCR5.

CONCLUSIONS:

Subject C135's early PCR and weak antibody results are consistent with limited infection with a poorly replicating nef/LTR-deleted strain of HIV-1. With his HLA-B57-restricted gag-specific CD8 and helper HLA-DR13-restricted CD4 T cell proliferative responses, C135 appears to have cleared his HIV-1 infection 37 years after transfusion.

• Authors: John Zaunders, Wayne B Dyer, Melissa Churchill, C Mee Ling Munier, Philip H Cunningham, Kazuo Suzuki, Kristin McBride, Will Hey-Nguyen, Kersten Koelsch, Bin Wang, Bonnie Hiener, Sarah Palmer, Paul R Gorry, Michelle Bailey, Yin Xu, Mark Danta, Nabila Seddiki, David A Cooper, Nitin K Saksena, John S Sullivan, Sean Riminton, Jenny Learmont, Anthony D Kelleher
• Journal: Journal of virus eradication (J Virus Erad) Vol. 5 Issue 2 Pg. 73-83 (Apr 01 2019) ISSN: 2055-6640 [Print] England
• PMID: 31191910 (Publication Type: Editorial)