Abstract
Cyclophilins are a family of proteins that bind cyclosporin A (CsA) and possess peptidyl-prolyl cis-trans isomerase activity. In addition, they are secreted by activated cells and act in a cytokine-like manner, presumably via signaling through a cell surface cyclophilin receptor. More recently, host- derived cyclophilin A (CyPA) has been shown to be incorporated into HIV-1 virions and its incorporation essential for viral infectivity. Here we present evidence supporting a role for viral-associated CyPA in the early events of HIV-1 infection. We report that HIV-1 infection of primary peripheral blood mononuclear cells can be inhibited by: (i) an excess of exogenously added CyPA; (ii) a CsA analogue unable to enter the cells; (iii) neutralizing antibodies to CyPA. Taken together with our observations that recombinant CyPA-induced mobilization of calcium in immortalized, as well as primary, CD4+ T lymphocytes, and that incubation of T cells with iodinated CyPA, followed by chemical cross-linking, resulted in the formation of a high molecular mass complex on the cell surface, these results suggest that HIV- 1-associated CyPA mediates an early event in viral infection via interaction with a cellular receptor. This interaction may present a target for anti-HIV therapies and vaccines.
| Original language | English |
|---|---|
| Pages (from-to) | 1758-1763 |
| Number of pages | 6 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 95 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Feb 17 1998 |
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ASJC Scopus subject areas
- Genetics
- General
Cite this
Role of cyclophilin A in the uptake of HIV-1 by macrophages and T lymphocytes. / Sherry, Barbara; Zybarth, Gabriele; Alfano, Massimo; Dubrovsky, Larisa; Mitchell, Robert; Rich, Daniel; Ulrich, Peter; Bucala, Richard; Cerami, Anthony; Bukrinsky, Michael.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 95, No. 4, 17.02.1998, p. 1758-1763.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Role of cyclophilin A in the uptake of HIV-1 by macrophages and T lymphocytes
AU - Sherry, Barbara
AU - Zybarth, Gabriele
AU - Alfano, Massimo
AU - Dubrovsky, Larisa
AU - Mitchell, Robert
AU - Rich, Daniel
AU - Ulrich, Peter
AU - Bucala, Richard
AU - Cerami, Anthony
AU - Bukrinsky, Michael
PY - 1998/2/17
Y1 - 1998/2/17
N2 - Cyclophilins are a family of proteins that bind cyclosporin A (CsA) and possess peptidyl-prolyl cis-trans isomerase activity. In addition, they are secreted by activated cells and act in a cytokine-like manner, presumably via signaling through a cell surface cyclophilin receptor. More recently, host- derived cyclophilin A (CyPA) has been shown to be incorporated into HIV-1 virions and its incorporation essential for viral infectivity. Here we present evidence supporting a role for viral-associated CyPA in the early events of HIV-1 infection. We report that HIV-1 infection of primary peripheral blood mononuclear cells can be inhibited by: (i) an excess of exogenously added CyPA; (ii) a CsA analogue unable to enter the cells; (iii) neutralizing antibodies to CyPA. Taken together with our observations that recombinant CyPA-induced mobilization of calcium in immortalized, as well as primary, CD4+ T lymphocytes, and that incubation of T cells with iodinated CyPA, followed by chemical cross-linking, resulted in the formation of a high molecular mass complex on the cell surface, these results suggest that HIV- 1-associated CyPA mediates an early event in viral infection via interaction with a cellular receptor. This interaction may present a target for anti-HIV therapies and vaccines.
AB - Cyclophilins are a family of proteins that bind cyclosporin A (CsA) and possess peptidyl-prolyl cis-trans isomerase activity. In addition, they are secreted by activated cells and act in a cytokine-like manner, presumably via signaling through a cell surface cyclophilin receptor. More recently, host- derived cyclophilin A (CyPA) has been shown to be incorporated into HIV-1 virions and its incorporation essential for viral infectivity. Here we present evidence supporting a role for viral-associated CyPA in the early events of HIV-1 infection. We report that HIV-1 infection of primary peripheral blood mononuclear cells can be inhibited by: (i) an excess of exogenously added CyPA; (ii) a CsA analogue unable to enter the cells; (iii) neutralizing antibodies to CyPA. Taken together with our observations that recombinant CyPA-induced mobilization of calcium in immortalized, as well as primary, CD4+ T lymphocytes, and that incubation of T cells with iodinated CyPA, followed by chemical cross-linking, resulted in the formation of a high molecular mass complex on the cell surface, these results suggest that HIV- 1-associated CyPA mediates an early event in viral infection via interaction with a cellular receptor. This interaction may present a target for anti-HIV therapies and vaccines.
UR - http://www.scopus.com/inward/record.url?scp=13144266687&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=13144266687&partnerID=8YFLogxK
U2 - 10.1073/pnas.95.4.1758
DO - 10.1073/pnas.95.4.1758
M3 - Article
C2 - 9465090
AN - SCOPUS:13144266687
VL - 95
SP - 1758
EP - 1763
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 4
ER -