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- Title
Genetic determinants of Nef-mediated CD4 and HLA class I down-regulation differences between HIV-1 subtypes B and C.
- Authors
Mann, Jaclyn K.; Omarjee, Saleha; Khumalo, Phumzile; Ndung'u, Thumbi
- Abstract
Background: HIV-1 subtype C Nef sequences have a significantly lower ability overall to down-regulate CD4 and HLA-I than subtype B Nef sequences. Here we investigated whether Nef amino acids differing in frequency between HIV-1 subtypes B and C explain lower CD4 and HLA-I down-regulation ability of subtype C. Findings: Subtype-specific mutations were introduced into representative subtype B and C Nef sequences and the CD4 and HLA-I down-regulation ability of these mutants was measured by flow cytometry in a CD4+ T cell line. Subtype C consensus 20I and subtype B consensus 20M reduced and increased HLA-I down-regulation respectively, and the S88G immune escape mutation (which is significantly more frequent in subtype C than subtype B) reduced CD4 and HLA-I down-regulation. Conclusions: Our data suggest that these subtype-specific differences may partly contribute to inter-subtype functional differences, and identification of an immune escape mutation – S88G – that impairs Nef function is of relevance to vaccine design.
- Subjects
HIV infections; AMINO acids; VIRAL replication; IMMUNE system; FLOW cytometry
- Publication
Virology Journal, 2015, Vol 12, Issue 1, p1
- ISSN
1743-422X
- Publication type
Article
- DOI
10.1186/s12985-015-0429-7