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This review describes the diverse array of pathways and molecular targets that are used by viruses to elude immune detection and destruction. These include targeting of pathways for major histocompatibility complex-restricted antigen presentation, apoptosis, cytokine-mediated signaling, and humoral immune responses. The continuous interactions between host and pathogens during their coevolution have shaped the immune system, but also the counter measures used by pathogens. Further study of their interactions should improve our ability to manipulate and exploit the various pathogens.

Human ES cells (hESC) exposed to bone morphogenic protein 4 (BMP4) in the absence of FGF2 have become widely used for studying trophoblast development, but the soundness of this model has been challenged by others, who concluded that differentiation was primarily toward mesoderm rather than trophoblast. Here we confirm that hESC grown under the standard conditions on a medium conditioned by mouse embryonic fibroblasts in the presence of BMP4 and absence of FGF2 on a Matrigel substratum rapidly convert to an epithelium that is largely KRT7+ within 48 h, with minimal expression of mesoderm markers, including T (Brachyury). Instead, they begin to express a series of trophoblast markers, including HLA-G, demonstrate invasive properties that are independent of the continued presence of BMP4 in the medium, and, over time, produce extensive amounts of human chorionic gonadotropin, progesterone, placental growth factor, and placental lactogen. This process of differentiation is not dependent on conditioning of the medium by mouse embryonic fibroblasts and is accelerated in the presence of inhibitors of Activin and FGF2 signaling, which at day 2 provide colonies that are entirely KRT7 + and in which the majority of cells are transiently CDX2 + . Colonies grown on two chemically defined media, including the one in which BMP4 was reported to drive mesoderm formation, also differentiate at least partially to trophoblast in response to BMP4. The experiments demonstrate that the in vitro BMP4/hESC model is valid for studying the emergence and differentiation of trophoblasts.A popular model for examining the early commitment of cells to the trophoblast (TR) lineage is based on the initial observation of Xu et al. (1), who noted that a group of related factors in the TGF-β family, especially bone morphogenic protein 4 (BMP4), was capable of causing human ES cells (hESC) to differentiate efficiently to TRs. This differentiation occurred without extensive generation of mesoderm, endoderm, and ectoderm derivatives, as judged by microarray analysis of transcribed genes, although a low level of expression of genes characteristic of mesoderm and endoderm did occur. This model has become widely used (2-13) to study an aspect of early human development that is not easily addressed otherwise because of lack of access to human embryos. Over the course of these studies it was demonstrated that the key to obtaining differentiation primarily to TR rather than to other lineages when using BMP4 as the triggering agent was to exclude FGF2, a factor required for maintenance of hESC (14-17). When BMP4 is provided simultaneously with FGF2, the morphological transition of the cells is altered (10), and the colonies begin to form a range of mesoderm and endoderm derivatives in addition to TR (18). This effect is probably achieved by FGF2 signaling through the MEK/ERK pathway, thereby preserving NANOG expression (19,20). This body of work suggests that optimal differentiation to TR can be achieved best by maximizing BMP4 signaling while simultaneous...

Preeclampsia is a pregnancy-specific disorder characterized by hypertension and excess protein excretion in the urine. It is an important cause of maternal and fetal morbidity and mortality worldwide. The disease is almost exclusive to humans and delivery of the pregnancy continues to be the only effective treatment. The disorder is probably multifactorial, although most cases of preeclampsia are characterized by abnormal maternal uterine vascular remodeling by fetally derived placental trophoblast cells. Numerous in vitro and animal models have been used to study aspects of preeclampsia, the most common being models of placental oxygen dysregulation, abnormal trophoblast invasion, inappropriate maternal vascular damage and anomalous maternal-fetal immune interactions. Investigations into the pathophysiology and treatment of preeclampsia continue to move the field forward, albeit at a frustratingly slow pace. There remains a pressing need for novel approaches, new disease models and innovative investigators to effectively tackle this complex and devastating disorder.