Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Jul 15;34(9):1325-1330.
doi: 10.1097/QAD.0000000000002559.

An HIV-1 Nef genotype that diminishes immune control mediated by protective human leucocyte antigen alleles

Francis Mwimanzi  1 , Isaac Ngare  1 , Mako Toyoda  1 , Masahiko Mori  2 , Jaclyn Mann  3 , Thumbi Ndung'u  3 , Phillip Goulder  2 , Takamasa Ueno  1
Affiliations

An HIV-1 Nef genotype that diminishes immune control mediated by protective human leucocyte antigen alleles

Francis Mwimanzi et al. AIDS. .

Abstract

Objectives: Certain human leucocyte antigen (HLA)-B alleles (protective alleles) associate with durable immune control of HIV-1, but with substantial heterogeneity in the level of control. It remains elusive whether viral factors including Nef-mediated immune evasion function diminish protective allele effect on viral control.

Design: The naturally occurring non-Ser variant at position 9 of HIV-1 subtype C Nef has recently exhibited an association with enhanced HLA-B downregulation function and decreased susceptibility to recognition by CD8 T cells. We therefore hypothesized this Nef genotype leads to diminished immune control mediated by protective HLA alleles.

Methods: Nef sequences were isolated from HIV-1 subtype C-infected patients harboring protective alleles and several Nef functions including downregulation of HLA-A, HLA-B, CD4, and SERINC5 were examined. Association between Nef non-Ser9 and plasma viral load was examined in two independent South African and Botswanan treatment-naïve cohorts.

Results: Nef clones isolated from protective allele individuals encoding Nef non-Ser9 variant exhibited greater ability to downregulate HLA-B when compared with the Ser9 variant, while other Nef functions including HLA-A, CD4, and SERINC5 downregulation activity were unaltered. By analyzing a cohort of South African participants chronically infected with subtype C HIV-1, Nef non-Ser9 associated with higher plasma viral load in patients harboring protective alleles. Corroboratively, the Nef non-Ser9 correlated with higher plasma viral load in an independent cohort in Botswana.

Conclusion: Taken together, our study identifies the Nef genotype, non-Ser9 that subverts host immune control in HIV-1 subtype C infection.

PubMed Disclaimer

References

    1. O’Brien WA, Hartigan PM, Martin D, Esinhart J, Hill A, Benoit S, et al. Changes in plasma HIV-1 RNA and CD4+ lymphocyte counts and the risk of progression to AIDS. Veterans affairs cooperative study group on AIDS. N Engl J Med 1996; 334:426–431.
    1. Thiebaut R, Matheron S, Taieb A, Brun-Vezinet F, Chene G, Autran B. Long-term nonprogressors and elite controllers in the ANRS CO5 HIV-2 cohort. AIDS 2011; 25:865–867.
    1. Pereyra F, Jia X, McLaren PJ, Telenti A, de Bakker PI, Walker BD, et al. The major genetic determinants of HIV-1 control affect HLA class I peptide presentation. Science 2010; 330:1551–1557.
    1. Fellay J, Shianna KV, Ge D, Colombo S, Ledergerber B, Weale M, et al. A whole-genome association study of major determinants for host control of HIV-1. Science 2007; 317:944–947.
    1. Kiepiela P, Leslie AJ, Honeyborne I, Ramduth D, Thobakgale C, Chetty S, et al. Dominant influence of HLA-B in mediating the potential co-evolution of HIV and HLA. Nature 2004; 432:769–775.

Publication types

Substances