Sequence Variations in Human Immunodeficiency Virus Type 1 Nef Are Associated with Different Stages of Disease
AUTOR(ES)
Kirchhoff, Frank
FONTE
American Society for Microbiology
RESUMO
nef alleles derived from a large number of individuals infected with human immunodeficiency virus type 1 (HIV-1) were analyzed to investigate the frequency of disrupted nef genes and to elucidate whether specific amino acid substitutions in Nef are associated with different stages of disease. We confirm that deletions or gross abnormalities in nef are rarely present. However, a comparison of Nef consensus sequences derived from 41 long-term nonprogressors and from 50 individuals with progressive HIV-1 infection revealed that specific variations are associated with different stages of infection. Five amino acid variations in Nef (T15, N51, H102, L170, and E182) were more frequently observed among nonprogressors, while nine features (an additional N-terminal PxxP motif, A15, R39, T51, T157, C163, N169, Q170, and M182) were more frequently found in progressors. Strong correlations between the frequency of these variations in Nef and both the CD4+-cell count and the viral load were observed. Moreover, analysis of sequential samples obtained from two progressors revealed that several variations in Nef, which were more commonly observed in patients with low CD4+-T-cell counts, were detected only during or after progression to immunodeficiency. Our results indicate that sequence variations in Nef are associated with different stages of HIV-1 infection and suggest a link between nef gene function and the immune status of the infected individual.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=112607Documentos Relacionados
- Association of Nef with the Human Immunodeficiency Virus Type 1 Core
- Characterization of Three nef-Defective Human Immunodeficiency Virus Type 1 Strains Associated with Long-Term Nonprogression
- Functional characterization of human immunodeficiency virus type 1 nef genes in patients with divergent rates of disease progression.
- Modulation of Different Human Immunodeficiency Virus Type 1 Nef Functions during Progression to AIDS
- Target Cell Populations of Human Immunodeficiency Virus Type 1 in Peripheral Blood Lymphocytes with Different Chemokine Receptors at Various Stages of Disease Progression