In this study, we demonstrate for the first time, the impact of DC-SIGN natural polymorphisms on its expression in placental cells and interaction with HIV-1 and provide compelling evidence to support an important role of DC-SIGN in IU HIV-1 infection. These findings raise the possibility that similar mechanisms may operate with other human pathogens known to interact with DC-SIGN and warrant further investigation. p24 Ag was measured by ELISA. Where indicated, cells were pre-incubated with anti-DC-SIGN (AZN-D1) or with mannan to inhibit DC-SIGN interaction with HIV-1. HIV-1 capture is shown relative to WT (WT = 100%). (D) HIV-1 transfer to T lymphocytes by DC-SIGN variants. Raji-transfectants were pulsed as in (C) and subsequently co-cultivated with activated human primary CD4 + T lymphocytes from two donors for 5 days. Virus release into the supernatant was measured by ELISA p24. Where indicated, cells were pre-incubated with AZN-D1. HIV-1 transmission is shown relative to WT (WT = 100%). Results are mean 6 SD of duplicates for each donor (D) or three independent experiments (C). Student's t test was used to calculate differences in % capture and transmission among Raji DC-SIGN transfectants L242V, R198Q and WT. doi:10.1371/journal.pone.0040706.g003 pGL2-Basic, the parental vector without a promoter. Expression of the DC-SIGN promoter constructs was calculated relative to the value of pGL2-Basic, which was arbitrarily set as 1. Data are mean 6 SD values of 3 independent experiments performed in triplicates and there were no significant differences in the relative expression between variants and wild-type (WT) as determined with Student's t test. (DOCX) Figure S2 HIV-1 capture by Raji transfectants (a) Dosedependent HIV-1 capture by Raji transfectants. Raji and Raji-H1 transfectants were incubated with 25, 50 and 100 ng of p24equivalent of HIV-1 HXBru-ADA for 2 h at 37uC, washed with cold PBS 1X and lysed in 0,5% Triton X-100. Cell-associated p24 contents were measured by ELISA. (b) Residual cell-associated HIV-1 over time. 3610 5 Raji-transfectants were exposed to 150 ng of p24-equivalent of HIV-1 HXBru-ADA for 2 h at 37uC, washed and incubated in fresh medium at 37uC for different time points (0, 1 h, 2 h, 4 h and 18 h). Cell-associated p24-contents were measured by ELISA after lysis in 0,5% Triton X-100. (c) Capture assay with HIV-1 JR-CSF . 3610 5 cells were incubated with 50 ng of p24-equivalent of HIV-1 JR-CSF for 2 h at 37uC, washed extensively with cold PBS 1X and lysed in 0,5% Triton X-100. Cell-associated p24 contents were measured by ELISA. Where indicated, cells were pre-incubated 30 min at 4uC with 20 mg/ml of anti-DC-SIGN (AZND1) or with mannan (200 mg/ml) to inhibit DC-SIGN interaction with HIV-1 before pulsing with HIV-1 JR-CSF . HIV-1 capture is shown relative to wild-type (WT = 100%). Data are mean 6 SD of 2 independent experiments performed in duplicates. Student's t test was used to calculate differences in % capture between the Raji DC-SIGN transfectants L242V, R198Q and WT. (DOCX) A New Model for Hendra Virus Encephalitis in the Mouse Hendra virus (HeV) infection in humans is characterized by an influenza like illness, which may progress to pneumonia or encephalitis and lead to death. The pathogenesis of HeV infection is poorly understood, and the lack of a mouse model has limited the opportunities for pathogenetic research. In this project we reassessed the role of mice as an animal model for HeV infection and found that mice are susceptible to HeV infection after intranasal exposure, with aged mice reliably developing encephalitic disease. We propose an anterograde route of neuroinvasion to the brain, possibly along olfactory nerves. This is supported by evidence for the development of encephalitis in the absence of viremia and the sequential distribution of viral antigen along pathways of olfaction in the brain of intranasally challenged animals. In our studies mice developed transient lower respiratory tract infection without progressing to viremia and systemic vasculitis that is common to other animal models. These studies report a new animal model of HeV encephalitis that will allow more detailed studies of the neuropathogenesis of HeV infection, particularly the mode of viral spread and possible sequestration within the central nervous system; investigation of mechanisms that moderate the development of viremia and systemic disease; and inform the development of improved treatment options for human patients. Hendra virus (HeV) causes serious systemic infection with pneumonia and encephalitis in humans, horses and various laboratory animals [1, 2, 3, 4] . It is a single-stranded, negative-sense RNA virus belonging to the family Paramyxoviridae and is classified within the genus Henipavirus which it shares with one other virus, Nipah virus (NiV). HeV first emerged in the Brisbane suburb of Hendra in 1994, where it caused the deaths of one human and fourteen horses [5] . Since then a further thirty four HeV outbreaks have been identified along the mid to north-eastern coast of Australia with infection of five more humans (of whom three died) and numerous horses [6, 7, 8, 9] . Pteropid bats have been identified as the reservoir host [10] , however epidemiological evidence does not support direct bat to human transmission. Horses have been an intermediate host in the transmission of disease to humans in all cases. There are as yet no readily available effective therapies or prophylaxis for HeV infection, either for use in humans or other susceptible animals.