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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
Polymorphisms in Nef associated with different clinical outcomes in HIV type 1 subtype C-infected children
AIDS Research and Human Retroviruses, Volume 23, No. 2, Year 2007
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Description
The human immunodeficiency virus type 1 (HIV-1) negative factor, or Nef, has a variety of functions that are important in viral pathogenesis. Sequence analysis has identified nef mutations that are linked to the rate of disease progression in adults and children infected with HIV-1 subtype B. Here we have sequenced and analysed HIV-1 subtype C nef sequences from 34 children with rapid (RP) or slow progressing (SP) disease and identified polymorphisms associated with disease stage including motifs involved in specific pathogenic functions. Unlike subtype B, insertions and deletions in the N-terminal variable region were observed exclusively in SP children (8 out of 25). Strong positive selection pressures were found in sites of known functional importance among SP sequences, whereas RP had strong negative selection across the gene. A lineage analysis of selection pressures indicated weaker pressure across the nef gene in SP sequences bearing a deletion in region 8-12, suggesting this deletion has functional importance in vivo. Together these results suggest a differential adaptation of certain Nef functions related to disease progression, some of which may be attributable to immune-imposed pressures. These data broadly reflect previous studies on subtype B, corroborate the decreased cytopathicity of SP viruses, but also highlight potential subtype differences that require further investigation. © Mary Ann Liebert, Inc.
Authors & Co-Authors
Walker, Polly R.
United Kingdom, Oxford
University of Oxford
South Africa, Johannesburg
National Institute for Communicable Diseases
Ketunuti, Melissa
United States, Stanford
Stanford University School of Medicine
Choge, Isaac A.
South Africa, Johannesburg
National Institute for Communicable Diseases
Meyers, Tammy M.M.
South Africa, Johannesburg
University of the Witwatersrand
Gray, Glenda E.
South Africa, Johannesburg
Chris Hani Baragwanath Hospital
Holmes, Edward C.
United States, University Park
Pennsylvania State University
Morris, Lynn
South Africa, Johannesburg
National Institute for Communicable Diseases
Statistics
Citations: 26
Authors: 7
Affiliations: 6
Identifiers
Doi:
10.1089/aid.2006.0080
ISSN:
08892229
Research Areas
Genetics And Genomics
Infectious Diseases
Maternal And Child Health