Genetic determinants of Nef-mediated CD4 and HLA class I down-regulation differences between HIV-1 subtypes B and C

• Published in: Virology journal Vol. 12; no. 1; p. 200
• Main Authors: Mann, Jaclyn K, Omarjee, Saleha, Khumalo, Phumzile, Ndung'u, Thumbi
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 25.11.2015; BioMed Central
• Subjects: Acquired immune deficiency syndrome; AIDS; AIDS vaccines; Amino Acid Substitution; Amino acids; CD4 Antigens - analysis; CD4-Positive T-Lymphocytes - chemistry; CD4-Positive T-Lymphocytes - virology; Cell Line; Cloning; DNA Mutational Analysis; Down-Regulation; Experiments; Flow Cytometry; Genotype; Histocompatibility Antigens Class I - analysis; HIV; HIV (Viruses); HIV-1 - classification; HIV-1 - genetics; HIV-1 - physiology; Host-Pathogen Interactions; Human immunodeficiency virus; Humans; Laboratories; Molecular Sequence Data; Mutagenesis; Mutagenesis, Site-Directed; Mutation; nef Gene Products, Human Immunodeficiency Virus - metabolism; Proteins; RNA, Viral - genetics; Sequence Analysis, DNA; Short Report; Studies; T cells
• ISSN: 1743-422X; 1743-422X
• DOI: 10.1186/s12985-015-0429-7

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. 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. 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.