Production of interferons and beta-chemokines by placental trophoblasts of HIV-1-infected women.
OBJECTIVE
The mechanism whereby the placental cells of a human immunodeficiency virus (HIV)-1-infected mother protect the fetus from HIV-1 infection is unclear. Interferons (IFNs) inhibit the replication of viruses by acting at various stages of the life cycle and may play a role in protecting against vertical transmission of HIV-1. In addition the beta-chemokines RANTES (regulated on activation T cell expressed and secreted), macrophage inflammatory protein-1-alpha (MIP-1alpha), and MIP-1beta can block HIV-1 entry into cells by preventing the binding of the macrophage-trophic HIV-1 strains to the coreceptor CCR5. In this study the production of IFNs and beta-chemokines by placental trophoblasts of HIV-1-infected women who were HIV-1 non-transmitters was examined.


METHODS
Placental trophoblastic cells were isolated from 29 HIV-1-infected and 10 control subjects. Supernatants of trophoblast cultures were tested for the production of IFNs and beta-chemokines by enzyme linked immunosorbent assay (ELISA). Additionally, HIV-1-gag and IFN-beta transcripts were determined by a semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) assay.


RESULTS
All placental trophoblasts of HIV-1-infected women contained HIV-1-gag transcripts. There were no statistical differences in the median constitutive levels of IFN-alpha and IFN-gamma produced by trophoblasts of HIV-1 infected and control subjects. In contrast, trophoblasts of HIV-1-infected women constitutively produced significantly higher levels of IFN-beta protein than trophoblasts of control subjects. Furthermore, the median levels of beta-chemokines produced by trophoblasts of HIV-infected and control women were similar.


CONCLUSIONS
Since there was no correlation between the placental HIV load and the production of interferons or beta-chemokines, the role of trophoblast-derived IFNs and beta-chemokines in protecting the fetus from infection with HIV-1 is not clear.
Lee
B N
BN
Department of Molecular Pathology, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Hammill
H
H
Popek
E J
EJ
Cron
S
S
Kozinetz
C
C
Paul
M
M
Shearer
W T
WT
Reuben
J M
JM
D018791:CD4 Lymphocyte Count; D019742:Chemokines, CC / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015658:HIV Infections / Q000276:immunology / Q000378:metabolism* / Q000635:transmission*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical; D016899:Interferon-beta / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007372:Interferons / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000276:immunology / Q000378:metabolism*; D011256:Pregnancy Outcome; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014327:Trophoblasts / Q000276:immunology / Q000378:metabolism*; D019562:Viral Load; D014779:Virus Replication / Q000235:genetics / Q000276:immunology
D019742:Chemokines, CC; D016899:Interferon-beta; D007371:Interferon-gamma; D007372:Interferons