Novel monoclonal antibodies to cyclosporine A: Characterization and epitope mapping with cyclosporine analogs and cyclophilin

Cacalano, Nicholas A.; Aggarwal, R.; Quesniaux, Valérie; Cleveland, William L.; Erlanger, Bernard F.

doi:10.1016/0161-5890(92)90162-q

Cited by 6 publications

(2 citation statements)

References 18 publications

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“…It was recently reported that the HIV-1 CA protein and CsA display a common epitope detected by a monoclonal antibody (14). The antibody recognizes N-methyl leucines 9 and 10 of the cyclic undecapeptide CsA (7). Interestingly, the peptide bond between these two residues isomerizes from cis to trans upon binding to cyclophilin (22,47), and it has been proposed that binding of cyclophilin A to HIV-1 Gag may induce similar structural transformations (14).…”

Section: Discussionmentioning

confidence: 99%

The human immunodeficiency virus type 1 capsid p2 domain confers sensitivity to the cyclophilin-binding drug SDZ NIM 811

Dorfman

Göttlinger

1996

J Virol

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Human immunodeficiency virus type 1 (HIV-1) specifically incorporates the host cell peptidyl-prolyl isomerase cyclophilin A into virions via contacts with the capsid (CA) domain of the Gag polyprotein Pr55 gag . The immunosuppressant drug cyclosporin A and the nonimmunosuppressive cyclosporin A analog SDZ NIM 811 bind to cyclophilin A and inhibit its incorporation into HIV-1 virions. Both drugs inhibit the virion association of cyclophilin A and the replication of HIV-1 with a similar dose dependence. In contrast, these compounds are inactive against other primate lentiviruses which do not incorporate cyclophilin A, such as simian immunodeficiency virus (SIV). To locate determinants which confer sensitivity to SDZ NIM 811, we generated chimeric proviruses between HIV-1 and SIV mac . A hybrid SIV mac which has the CA-p2 domain of the Gag polyprotein replaced by the corresponding domain from HIV-1 replicated in an established CD4 ؉ cell line and in human but not macaque peripheral blood mononuclear cells. The transfer of the HIV-1 CA-p2 domain to SIV mac led to the efficient incorporation of cyclophilin A, and SDZ NIM 811 effectively inhibited both the virion association of cyclophilin A and the spread of the hybrid virus in infected cultures.We conclude that the HIV-1 CA-p2 domain contains determinants which confer the necessity to interact with cyclophilin A for efficient virus replication. Furthermore, our data show that the CA-p2 domain can play a crucial role in species tropism.

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Section: Discussionmentioning

confidence: 99%

The human immunodeficiency virus type 1 capsid p2 domain confers sensitivity to the cyclophilin-binding drug SDZ NIM 811

Dorfman

Göttlinger

1996

J Virol

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“…4A) for 1 h at 37ЊC and then incubated with the p24-coated plates for 90 min at 37ЊC. Bound B11 1.4 was then detected in a peroxidase reaction as previously described (1). The specificity of B11 1.4 binding to native p24 was demonstrated by the linear inhibition of binding by cyclosporine (Fig.…”

mentioning

confidence: 99%

Cyclophilin binding to the human immunodeficiency virus type 1 Gag polyprotein is mimicked by an anti-cyclosporine antibody

Franke

Chen

Tatsis

et al. 1995

J Virol

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Human immunodeficiency virus type 1 is unique among retroviruses in that infectivity requires specific incorporation into virions of the cellular protein cyclophilin A through interactions with the Gag polyprotein. Here we show that monoclonal antibody B11 1.4, which recognizes a cyclophilin-binding epitope on cyclosporine, detects denatured or native human immunodeficiency virus type 1 capsid. B11 1.4 does not recognize the capsids of other retroviruses, and binding is inhibited by cyclosporine or by cyclophilin A.

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Do we know the site of action of cyclosporin?

Erlanger

1992

Immunology Today

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Novel monoclonal antibodies to cyclosporine A: Characterization and epitope mapping with cyclosporine analogs and cyclophilin

Cited by 6 publications

References 18 publications

The human immunodeficiency virus type 1 capsid p2 domain confers sensitivity to the cyclophilin-binding drug SDZ NIM 811

The human immunodeficiency virus type 1 capsid p2 domain confers sensitivity to the cyclophilin-binding drug SDZ NIM 811

Cyclophilin binding to the human immunodeficiency virus type 1 Gag polyprotein is mimicked by an anti-cyclosporine antibody

Do we know the site of action of cyclosporin?

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