Sensitivity to Inhibition by β -chemokines Correlates with Biological Phenotypes of Primary HIV-1 Isolates

• Published in: Proceedings of the National Academy of Sciences - PNAS 1996-12, Vol.93 (26), p.15382-15387
• Main Authors: Jansson, Marianne, Popovic, Mikulas, Karlsson, Anders, Cocchi, Fiorenza, Rossi, Paolo, Albert, Jan, Wigzell, Hans
• Format: Article
• Language: English
• Subjects: Acquired Immunodeficiency Syndrome - virology; AIDS; Amino Acid Sequence; Amino acids; Antigens; Biological Sciences; Cells, Cultured; Chemokine CCL3; Chemokine CCL4; Chemokine CCL5 - pharmacology; Chemokines; Disease Progression; DNA, Viral - chemistry; Giant Cells; HIV; HIV 1; HIV Core Protein p24 - biosynthesis; HIV Core Protein p24 - chemistry; HIV Infections - virology; HIV-1 - drug effects; HIV-1 - isolation & purification; HIV-1 - physiology; Human immunodeficiency virus; human immunodeficiency virus 1; Humans; Infections; Isols; Lymphocytes - immunology; Lymphocytes - virology; Macrophage Inflammatory Proteins - pharmacology; Medical research; Medicin och hälsovetenskap; Molecular Sequence Data; Phenotype; Phenotypes; Polymerase Chain Reaction; Recombinant Proteins - pharmacology; T lymphocytes; Virus Replication - drug effects; Viruses
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.93.26.15382

Primary HIV-1 isolates were evaluated for their sensitivity to inhibition by β -chemokines RANTES (regulated upon activation, normal T-cell expressed and secreted), macrophage inflammatory protein 1α (MIP-1α ), and MIP-1β . Virus isolates of both nonsyncytium-inducing (NSI) and syncytium-inducing (SI) biological phenotypes recovered from patients at various stages of HIV-1 infection were assessed, and the results indicated that only the isolates with the NSI phenotype were substantially inhibited by the β -chemokines. More important to note, these data demonstrate that resistance to inhibition by β -chemokines RANTES, MIP-1α , and MIP-1β is not restricted to T cell line-adapted SI isolates but is also a consistent property among primary SI isolates. Analysis of isolates obtained sequentially from infected individuals in whom viruses shifted from NSI to SI phenotype during clinical progression exhibited a parallel loss of sensitivity to β -chemokines. Loss of virus sensitivity to inhibition by β -chemokines RANTES, MIP-1α , and MIP-1β was furthermore associated with changes in the third variable (V3) region amino acid residues previously described to correlate with a shift of virus phenotype from NSI to SI. Of interest, an intermediate V3 genotype correlated with a partial inhibition by the β -chemokines. In addition, we also identified viruses sensitive to RANTES, MIP-1α , and MIP-1β of NSI phenotype that were isolated from individuals with AIDS manifestations, indicating that loss of sensitivity to β -chemokines inhibition and shift in viral phenotype are not necessarily prerequisites for the pathogenesis of HIV-1 infection.