Leukemia inhibitory factor inhibits HIV-1 replication and is upregulated in placentae from nontransmitting women.
The placenta may play a critical role in inhibiting vertical transmission of HIV-1. Here we demonstrate that leukemia inhibitory factor (LIF) is a potent endogenous HIV-1-suppressive factor produced locally in placentae. In vitro, LIF exerted a potent, gp130-LIFRbeta-dependent, HIV coreceptor-independent inhibition of HIV-1 replication with IC50 values between 0.1 pg/ml and 0.7 pg/ml, depending on the HIV-1 isolate. LIF also inhibited HIV-1 in placenta and thymus tissues grown in ex vivo organ culture. The level of LIF mRNA and the incidence of LIF protein-expressing cells were significantly greater in placentae from HIV-1-infected women who did not transmit HIV-1 to their fetuses compared with women who transmitted the infection, but they were not significantly different from placentae of uninfected mothers. These findings demonstrate a novel pathway for endogenous HIV suppression that may prove to be an effective immune therapy for HIV infection.
Patterson
B K
BK
Department of Pediatrics, Division of Infectious Diseases, Children's Memorial Hospital/Northwestern University Medical School, 2300 Children's Plaza #51, Chicago, Illinois 60614, USA. bpatterson@childrensmemorial.org
Behbahani
H
H
Kabat
W J
WJ
Sullivan
Y
Y
O'Gorman
M R
MR
Landay
A
A
Flener
Z
Z
Khan
N
N
Yogev
R
R
Andersson
J
J
D000328:Adult; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D058966:Contactins; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D015870:Gene Expression; D006131:Growth Inhibitors / Q000494:pharmacology / Q000502:physiology*; D015658:HIV Infections / Q000635:transmission; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; D008222:Lymphokines / Q000494:pharmacology / Q000502:physiology*; D009000:Monocytes / Q000187:drug effects; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism; D010920:Placenta / Q000276:immunology / Q000378:metabolism* / Q000821:virology; D012333:RNA, Messenger / Q000032:analysis; D018121:Receptors, Cytokine / Q000378:metabolism; D053606:Receptors, OSM-LIF; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation; D019562:Viral Load; D014779:Virus Replication / Q000187:drug effects
D058966:Contactins; D004279:DNA, Viral; D006131:Growth Inhibitors; D015850:Interleukin-6; C507837:LIF protein, human; C507840:LIFR protein, human; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; D008222:Lymphokines; D019006:Neural Cell Adhesion Molecules; D012333:RNA, Messenger; D018121:Receptors, Cytokine; D053606:Receptors, OSM-LIF