TY - JOUR
T1 - Proteomic Analyses Associate Cystatin B with Restricted HIV-1 Replication in Placental Macrophages
AU - Luciano-Montalvo, C.
AU - Ciborowski, P.
AU - Duan, F.
AU - Gendelman, H. E.
AU - Meléndez, L. M.
N1 - Funding Information:
We acknowledge the members of Dr. Melendez's laboratory and all NeuroAIDS members at the University of Puerto Rico Medical Sciences Campus, for their support of this project. We thank the NIH AIDS Research and Reference Reagent Program for the HIV-BAL isolate. This work was supported by NIH grants: NINDS 1 U54NS430, NIGMS MBRS-SCORE-SO6GMO822, NCRR-RCMI-CRC P20RR11126, RCMI-G12RR03051, and MBRS-RISE GM61838.
PY - 2008/12
Y1 - 2008/12
N2 - Mononuclear phagocytes (MP; monocytes, tissue macrophages, and dendritic cells) are reservoirs, vehicles of dissemination, and targets for persistent HIV infection. However, not all MP population equally support viral growth. Such differential replication is typified by the greater ability of placental macrophages (PM), as compared to blood borne monocyte-derived macrophages (MDM), to restrict viral replication. Since cytosolic protein patterns can differentiate macrophage subtypes, we used a proteomics approach consisting of surface-enhanced laser desorption ionization time-of-flight (SELDI-TOF), tandem mass spectrometry, and Western blots to identify differences between the uninfected and HIV-infected PM and MDM protein profiles linked to viral growth. We performed proteome analysis of PM in the molecular range of 5-20 kDa. We found that a SELDI-TOF protein peak with an m/z of 11,100, which was significantly lower in uninfected and HIV-infected PM than in MDM, was identified as cystatin B (CSTB). Studies of siRNA against CSTB treatment in MDM associated its expression with HIV replication. These data demonstrate that the low molecular weight placental macrophage cytosolic proteins are differentially expressed in HIV-infected PM and MDM and identify a potential role for CSTB in HIV replication. This work also serves to elucidate a mechanism by which the placenta protects the fetus from HIV transmission.
AB - Mononuclear phagocytes (MP; monocytes, tissue macrophages, and dendritic cells) are reservoirs, vehicles of dissemination, and targets for persistent HIV infection. However, not all MP population equally support viral growth. Such differential replication is typified by the greater ability of placental macrophages (PM), as compared to blood borne monocyte-derived macrophages (MDM), to restrict viral replication. Since cytosolic protein patterns can differentiate macrophage subtypes, we used a proteomics approach consisting of surface-enhanced laser desorption ionization time-of-flight (SELDI-TOF), tandem mass spectrometry, and Western blots to identify differences between the uninfected and HIV-infected PM and MDM protein profiles linked to viral growth. We performed proteome analysis of PM in the molecular range of 5-20 kDa. We found that a SELDI-TOF protein peak with an m/z of 11,100, which was significantly lower in uninfected and HIV-infected PM than in MDM, was identified as cystatin B (CSTB). Studies of siRNA against CSTB treatment in MDM associated its expression with HIV replication. These data demonstrate that the low molecular weight placental macrophage cytosolic proteins are differentially expressed in HIV-infected PM and MDM and identify a potential role for CSTB in HIV replication. This work also serves to elucidate a mechanism by which the placenta protects the fetus from HIV transmission.
KW - Cystatin B
KW - HIV
KW - MDM
KW - Placental macrophages
KW - SOD
KW - siRNA
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U2 - 10.1016/j.placenta.2008.09.005
DO - 10.1016/j.placenta.2008.09.005
M3 - Article
C2 - 18951626
AN - SCOPUS:56249108747
SN - 0143-4004
VL - 29
SP - 1016
EP - 1023
JO - Placenta
JF - Placenta
IS - 12
ER -