Functional association of cyclophilin A with HIV-1 virions

  title={Functional association of cyclophilin A with HIV-1 virions},
  author={Markus Thali and Anatoly A. Bukovsky and E Kondo and Brigitte Rosenwlrth and Christopher T Walsh and Joseph G. Sodroski and Heinrich G{\"o}ttlinger},
CYCLOPHILINS are a family of proteins that bind the immunosuppressant cyclosporin A, possess peptidyl–prolylcis–trans isomerase activity, and assist in the folding of proteins1–6. Human cyclophilins A and B are host cell proteins that bind specifically to the HIV-1 Gag polyprotein p55gag in vitro7. Here we report that viral particles formed by p55gag, in contrast to particles formed by the Gag polyproteins of other retroviruses, contain significant amounts of cyclophilin A. Sequences in the… 

Role of cyclophilin A in the uptake of HIV-1 by macrophages and T lymphocytes.

It is reported that HIV-1 infection of primary peripheral blood mononuclear cells can be inhibited by an excess of exogenously added CyPA; a CsA analogue unable to enter the cells; and neutralizing antibodies to CyPA.

Target Cell Cyclophilin A Modulates Human Immunodeficiency Virus Type 1 Infectivity

It is clearly demonstrated that target cell CypA, and not producer cell CyA, is important for HIV-1 CA-mediated function, and inhibition of HIV- 1 infectivity resulting from virion production in the presence of CsA occurs independently of the CA-CypA interaction.

Immunophilins and HIV-1 infection

P24 antigen ELISA and real-time PCR measurements demonstrated that exogenously added immunophilins do not influence HIV-1 infection and may conclude that endogenous CypA exerts its action after reverse transcription but before virus maturation, probably during capsid formation.

Cyclophilin A Interacts with HIV-1 Vpr and Is Required for Its Functional Expression*

This study shows that in addition to the interaction between CypA and HIV-1 capsid occurring during early steps in virus replication, CypA is also important for the de novo synthesis of Vpr and that in the absence of CypA activity, the Vpr-mediated cell cycle arrest is completely lost in HIV- 1-infected T cells.

Cyclosporine A-resistant human immunodeficiency virus type 1 mutants demonstrate that Gag encodes the functional target of cyclophilin A

These experiments demonstrate that, in addition to its ability to package cyclophilin A into virions, gag encodes the functional target of cyclosporine A, indicating that the drug-resistant mutants do not require virion-associated cyclophin A to initiate infection.

Active-site residues of cyclophilin A are crucial for its incorporation into human immunodeficiency virus type 1 virions

In vivo evidence is provided that HIV-1 CA interacts with the active site of CyPA, providing in vivo evidence that active-site residues are also involved in the interaction with HIV- 1 CA.

Transfer of the HIV-1 cyclophilin-binding site to simian immunodeficiency virus from Macaca mulatta can confer both cyclosporin sensitivity and cyclosporin dependence.

This study provides direct in vivo evidence that the exposed loop between helices IV and V of HIV-1 CA not merely constitutes a docking site for CyPA but is a functional target of this cellular protein.

Cyclophilin Interactions with Incoming Human Immunodeficiency Virus Type 1 Capsids with Opposing Effects on Infectivity in Human Cells

It is demonstrated that the presence of CypA in the target and not the virus-producing cell enhances HIV-1 infectivity, and disruption of the CypA-CA interaction with cyclosporine A (CsA) inhibits HIV- 1 infectivity only if the target cell expresses CypA.

Cyclophilin B enhances HIV-1 infection.

Role of cyclophilin A in HIV replication

The binding of CypA to CA increases HIV-1 infectivity in human cells, but promotes an anti-HIV-1 restriction activity in cells from nonhuman primates, which changes the understanding of how CypA modulates HIV- 1 infectivity.



Cyclophilin: a specific cytosolic binding protein for cyclosporin A.

Isolation of cyclophilin from the cytosol of thymocytes suggests that the immunosuppressive activity of cyclosporin A is mediated by an intracellular mechanism, not by a membrane-associated mechanism.

Cellular proteins bound to immunodeficiency viruses: implications for pathogenesis and vaccines.

The specific, selective association of these cellular proteins in a physiologically relevant manner has major implications for the understanding of the infection process and the pathogenesis of immunodeficiency viruses and should be considered in the design of vaccines.

Role of the matrix protein in the virion association of the human immunodeficiency virus type 1 envelope glycoprotein

It is reported here that the HIV-1 capsid-Env glycoprotein association is very sensitive to minor alterations in the MA protein, and the results indicate that most of the MA domain of the Gag precursor, except for its carboxy terminus, is essential for this association.

Inhibition of human immunodeficiency virus type 1 replication by SDZ NIM 811, a nonimmunosuppressive cyclosporine analog

The potent and selective anti-HIV-1 activity of SDZ NIM 811 and its favorable pharmacokinetic behavior together with its lower nephrotoxicity than that of cyclosporine make this compound a promising candidate for development as an anti-hIV drug.

Peptidyl-prolyl cis-trans isomerase is the cyclosporin A-binding protein cyclophilin

It is proposed that the peptidyl-prolyl cis-trans isomerizing activity of PPIase may be involved in events, such as those occurring early in T-cell activation, that are suppressed by cyclosporin A.

Cyclophilin and peptidyl-prolyl cis-trans isomerase are probably identical proteins

The results indicate that this enzyme is probably identical to cyclophilin, a recently discovered mammalian protein which binds tightly to cyclosporin A (CsA), which is thought to be linked to the immunosuppressive action of CsA.

Functional domains of the capsid protein of human immunodeficiency virus type 1

Results indicate that CA domain sequences N terminal to the MHR are essential for the morphogenesis of the mature cone-shaped core of the human immunodeficiency virus type 1 Gag polyprotein.