Sensitivity to inhibition by beta-chemokines correlates with biological phenotypes of primary HIV-1 isolates - PubMed (original) (raw)

Comparative Study

Sensitivity to inhibition by beta-chemokines correlates with biological phenotypes of primary HIV-1 isolates

M Jansson et al. Proc Natl Acad Sci U S A. 1996.

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.

PubMed Disclaimer

Figures

Figure 1

Figure 1

Sensitivity to β-chemokines of primary HIV-1 isolates with either NSI or SI biological phenotype. Percentage of HIV-1 p24 release, in relation to controls, of β-chemokine-exposed virus cultures of (a) NSI phenotype or (b) SI phenotype.

Figure 2

Figure 2

Sensitivity to β-chemokine-mediated replication inhibition of primary HIV-1 isolates with different biological phenotypes obtained sequentially from individual patients. Percentage of p24 release, in relation to controls, of β-chemokine-exposed virus cultures with (a) NSI phenotype or after switch with (b) SI phenotype.

Figure 3

Figure 3

V3 region amino acid sequences obtained from viruses losing β-chemokine sensitivity simultaneously with a switch from NSI to SI phenotype in infected individuals. V3 amino acid residues are numbered according to the HIV-1MN sequence presented in the Los Alamos data base (35). A dash (-) indicates an amino acid identical to that present in the V3 sequence of the early isolate obtained from a corresponding individual, and a gap was introduced to align the sequences and is pointed out by a dot (.). Sequence heterogeneity is indicated by assigning two amino acids at the same position.

Figure 4

Figure 4

Sensitivity to chemokine-mediated replication inhibition of primary HIV-1 isolates with NSI phenotype obtained sequentially from three individual patients with AIDS. Percentage of p24 release, in relation to controls, of chemokine-exposed virus isolates obtained from patients F (a), G (b), and H (c).

Similar articles

Cited by

References

    1. Åsjö B, Morfeldt-Månson L, Albert J, Biberfeld G, Karlsson A, Lidman K, Fenyö E-M. Lancet. 1986;ii:660–662. - PubMed
    1. Fenyö E-M, Morfeldt-Månson L, Chiodi F, Lind B, von Gegerfelt A, Albert J, Olausson E, Åsjö B. J Virol. 1988;62:4414–4419. - PMC - PubMed
    1. Cheng-Mayer C, Seto D, Tateno M, Levy J A. Science. 1988;240:80–82. - PubMed
    1. Tersmette M, de Goede R E Y, Al B J M, Winkel I N, Gruters R A, Cuypers H T, Huisman H G, Miedema F. J Virol. 1988;62:2026–2032. - PMC - PubMed
    1. Schwartz S, Felber B, Fenyö E M, Pavlakis G N. Proc Natl Acad Sci USA. 1989;86:7200–7203. - PMC - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources