Conservation of the central proline-rich (PxxP) motifs of human immunodeficiency virus type 1 Nef protein during the disease progression in two hemophiliac patients

• Published in: FEBS letters 1999-10, Vol.459 (3), p.399-404
• Main Authors: Asamitsu, Kaori, Morishima, Takashi, Tsuchie, Hideaki, Kurimura, Takashi, Okamoto, Takashi
• Format: Article
• Language: English
• Subjects: AIDS; AIDS, acquired immunodeficiency syndrome; AIDS/HIV; Amino Acid Sequence; CD4 Antigens - metabolism; Conserved Sequence; Disease Progression; Down-Regulation; Evolution, Molecular; Gene Products, nef - chemistry; Gene Products, nef - classification; Gene Products, nef - genetics; Gene Products, nef - metabolism; Genetic Variation; Hemophilia A - complications; Hemophilia A - metabolism; Hemophilia A - virology; Histocompatibility Antigens Class I - metabolism; HIV Infections - complications; HIV Infections - virology; HIV-1; HIV-1 - genetics; HIV-1 - metabolism; HIV-1, human immunodeficiency virus type 1; Humans; Molecular evolution; Molecular Sequence Data; nef; nef Gene Products, Human Immunodeficiency Virus; PBMC, peripheral blood mononuclear cells; PCR, polymerase chain reaction; Peptides - chemistry; Peptides - genetics; PHA, phytohaemagglutinin; Phylogeny; Proline-Rich Protein Domains; Protein Conformation; Sequence Analysis; Sequence Homology, Amino Acid; SH3 ligand; SH3, Src homology region 3; Time Factors
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/S0014-5793(99)01288-0

The nef gene is considered to play a crucial role in the development of acquired immunodeficiency syndrome (AIDS). In this study, we analyzed the sequence of nef quasispecies obtained from replication-competent HIV-1 isolates from two Japanese hemophiliac patients infected with HIV-1. At least 10 nef clones were isolated at each time point and a total of 75 individual nef quasispecies were sequenced. We observed a gradual increase in genetic diversity of the nef gene over time. Among the various functional regions of Nef protein, myristoylation site and the central PXXP (SH3 ligand) motifs were well conserved. The scattered regions responsible for downregulation of CD4 and class I MHC were also conserved. These data suggest that these functions of Nef may be involved throughout the disease process.