title: Sensitivity to inhibition by beta-chemokines correlates with biological phenotypes of primary HIV-1 isolates.
abstract: Primary HIV-1 isolates were evaluated for their sensitivity to inhibition by beta-chemokines RANTES (regulated upon activation, normal T-cell expressed and secreted), macrophage inflammatory protein 1 alpha (MIP-1 alpha), and MIP-1 beta. 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 beta-chemokines. More important to note, these data demonstrate that resistance to inhibition by beta-chemokines RANTES, MIP-1 alpha, and MIP-1 beta 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 beta-chemokines. Loss of virus sensitivity to inhibition by beta-chemokines RANTES, MIP-1 alpha, and MIP-1 beta 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 beta-chemokines. In addition, we also identified viruses sensitive to RANTES, MIP-1 alpha, and MIP-1 beta of NSI phenotype that were isolated from individuals with AIDS manifestations, indicating that loss of sensitivity to beta-chemokine inhibition and shift in viral phenotype are not necessarily prerequisites for the pathogenesis of HIV-1 infection.
authors.affiliation: Microbiology and Tumorbiology Center, Karolinska Institute, Stockholm, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Jansson
authors.forename: M
authors.initials: M
authors.lastname: Popovic
authors.forename: A
authors.initials: A
authors.lastname: Karlsson
authors.forename: F
authors.initials: F
authors.lastname: Cocchi
authors.forename: P
authors.initials: P
authors.lastname: Rossi
authors.forename: J
authors.initials: J
authors.lastname: Albert
authors.forename: H
authors.initials: H
authors.lastname: Wigzell
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000821:virology*; D000595:Amino Acid Sequence; D002478:Cells, Cultured; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000494:pharmacology*; D004279:DNA, Viral / Q000737:chemistry; D018450:Disease Progression; D015726:Giant Cells; D016655:HIV Core Protein p24 / Q000096:biosynthesis* / Q000737:chemistry; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects / Q000302:isolation & purification / Q000502:physiology*; D006801:Humans; D008214:Lymphocytes / Q000276:immunology / Q000821:virology*; D019402:Macrophage Inflammatory Proteins / Q000494:pharmacology*; D008969:Molecular Sequence Data; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes; D014779:Virus Replication / Q000187:drug effects
chemical_list: D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D004279:DNA, Viral; D016655:HIV Core Protein p24; D019402:Macrophage Inflammatory Proteins; D011994:Recombinant Proteins