Possible clearance of transfusion-acquired nef/LTR-deleted attenuated HIV-1 infection by an elite controller with CCR5 Δ32 heterozygous and HLA-B57 genotype
Year: 2019
Type: article
Study design: Case Report
Abstract: 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. 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. 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. 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.
Source: Journal of Virus Eradication
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
Institutions: UNSW Sydney, St Vincent's Hospital Sydney, Kirby Institute, The University of Sydney, Australian Red Cross Lifeblood, RMIT University, Ingham Institute, Westmead Institute for Medical Research, Université Paris-Est Créteil, Institut de Recherche Vaccinale, China National GeneBank, Concord Repatriation General Hospital
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,950
OpenAlex ID: W3023952797