HIV-1 Nef breaches placental barrier in rat model

PLoS One. 2012;7(12):e51518. doi: 10.1371/journal.pone.0051518. Epub 2012 Dec 11.


The vertical transmission of HIV-1 from the mother to fetus is known, but the molecular mechanism regulating this transmission is not fully characterized. The fetus is highly protected by the placenta, which does not permit microbial pathogens to cross the placental barrier. In the present study, a rat model was established to observe the effect of HIV-1 protein Nef on placental barrier. Evans blue dye was used to assay permeability of placental barrier and fourteen day pregnant Sprague Dawley rats were injected intravenously with 2% Evans blue dye along with various concentrations of recombinant Nef. After an hour, animals were sacrificed and dye migration was observed through the assimilation of peripheral blood into fetus. Interestingly, traces of recombinant Nef protein were detected in the embryo as well as amniotic fluid and amniotic membrane along with placenta and uterus. Our study indicates that recombinant HIV-1-Nef protein breaches the placental barrier and allows the migration of Evans blue dye to the growing fetus. Further the concentration of Nef protein in blood is directly proportional to the intensity of dye migration and to the amount of Nef protein detected in uterus, placenta, amniotic membrane, amniotic fluid and embryo. Based on this study, it can be concluded that the HIV-1 Nef protein has a direct effect on breaching of the placental barrier in the model we have established in this study. Our observations will be helpful to understand the molecular mechanisms related to this breach of placental barrier by Nef in humans and may be helpful to identify specific Nef inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amniotic Fluid / metabolism
  • Amniotic Fluid / virology
  • Animals
  • Disease Models, Animal
  • Female
  • HIV Infections* / transmission
  • HIV Infections* / virology
  • HIV-1* / genetics
  • HIV-1* / pathogenicity
  • Humans
  • Infectious Disease Transmission, Vertical*
  • Placenta / virology
  • Pregnancy
  • Rats
  • Rats, Sprague-Dawley
  • Uterus / virology
  • nef Gene Products, Human Immunodeficiency Virus* / analysis
  • nef Gene Products, Human Immunodeficiency Virus* / metabolism


  • nef Gene Products, Human Immunodeficiency Virus

Grant support

The first author was supported by a fellowship from the Council of Scientific and Industrial Research, New Delhi. This manuscript is an outcome of the research funds provided by the Council of Scientific and Industrial Research, New Delhi, and grants from Ministry of Health and Alternative Animal Model (NWP034). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.