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AIDS Res Hum Retroviruses. 2017 Jun;33(6):558-566. doi: 10.1089/AID.2016.0184. Epub 2017 Jan 31.

Correlation of Antibody Responses to a Peptide Antigen gp120-C5501-512/gp41732-744 with HIV Disease Progression.

Author information

1
1 Bionor Pharma AS , Oslo, Norway .
2
2 St. George's, University of London , Institute of Infection and Immunity, London, United Kingdom .
3
3 Department of Virology, The Norwegian Institute of Public Health , Oslo, Norway .
4
4 Department of Medicine, Institute of Human Virology, University of Maryland School of Medicine , Baltimore, Maryland.
5
5 State Reference Laboratory of HIV Diagnostics, West-Tallinn Central Hospital , Estonia .
6
6 Bionor Laboratories AS , Skien, Norway .
7
7 Celgene Corp./Celgene Global Health , Summit, New Jersey.

Abstract

Antibodies to the carboxy-terminal constant (C5) region 5 of the HIV-1 envelope glycoprotein gp120 have previously been associated with slow disease progression. This is one of the regions on gp120 that interact with the transmembrane glycoprotein, gp41, anchoring it to the viral and infected cell membrane. This study analyzed humoral responses to a novel heterodimeric peptide construct comprising the C5501-512 region and a compatible region on gp41732-744. Antibody levels to C5501-512/gp41732-744 were associated with slow disease progression in a treatment naive historical longitudinal cohort from Norway (n = 32; p = .00001). Elevated anti-C5501-512/gp41732-744 antibody levels correlated with moderate viral load (VL) (50-10,000 copies/ml) in a cohort, including natural viral suppressors (NVS) in the Unites States (n = 58; p = .002). Analysis of HIV-positive sera from treatment naive patients in Estonia (n = 300) showed an inverse correlation between anti-C5501-512/gp41732-744 antibodies and VL when comparing VL 2,000-10,000 copies/ml with VL >10,000 (p = .050). Further mapping using peptide inhibition of antibody binding revealed that responses to the C5501-506 subdomain correlated with preserved CD4 counts (n = 55; p = .0012) irrespective of VL in this cohort. The C5 region encompassing C5501-506 shows sequence similarity to the shared epitope (SE) of certain HLA-DR associated with immune dysfunction. Partial antigenic cross-reactivity between SE and C5 is indicated by partial inhibition of NVS antibody binding using SE 15-mer peptide (median 65% inhibition), the C5501-506 6-mer peptide (79% inhibition), and binding of rheumatoid arthritis patient sera to both SE and C5 peptide sequences. The potential influence of these observations on HIV-1 pathogenesis remains to be determined.

KEYWORDS:

HIV envelope glycoproteins; HIV pathogenesis; antibody; immune activation; immune response

PMID:
28051320
DOI:
10.1089/AID.2016.0184
[Indexed for MEDLINE]

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