Читать книгу Principles of Virology, Volume 2 - Jane Flint, S. Jane Flint - Страница 76

A primary route by which a virus can be vertically transmitted from mother to offspring is to cross the placenta. Thus, in pregnant females, viremia may result in infection of the developing fetus. Maternal immune cells do not traverse the placental barrier, though these immune cells could bring virus into proximity with the placenta. Transplacental infections are distinct from perinatal infections, in which the virus is acquired via contact with maternal blood as the baby is delivered through the birth canal.

While some perinatal infections can be avoided by Caesarian delivery, in utero infections cannot. Historically, the primary transplacental viral infections of concern were rubella, cytomegalovirus, and herpes simplex virus. These viruses, along with the parasite Toxoplasma, comprised the four pathogens once defined by the acronym TORCH. Infection by any of these pathogens poses a substantial threat to the fetus. For example, the risk of fetal infection in mothers who are infected with rubella virus during the first trimester is approximately 80%. Similarly, intrauterine transmission of human cytomegalovirus occurs in approximately 40% of pregnant women with primary infection.

The recent Zika virus outbreak and appearance of birth defects in children born following in utero infection focused greater attention on transplacental virus infections (Fig. 2.10). The placenta is the sole barrier and conduit between the maternal and fetal blood supply and is responsible for gas, waste, and nutrient exchange throughout pregnancy, and its morphology and constitution change throughout pregnancy. Syncytiotrophoblasts lie at the maternal-fetal blood interface and are in direct contact with maternal blood; they are therefore crucial for protecting the fetus from circulating pathogens. Indeed, the syncytiotrophoblast layer is highly resistant to viral infections, including by teratogenic viruses such as rubella, cytomegalovirus, and Zika virus. The mechanisms by which teratogenic viruses cross the placenta are largely unknown, and there may be multiple mechanisms of trans mission to the fetus. Some pathways that have been proposed to allow for viral vertical transmission include traversing the syncytiotrophoblast layer by antibody-dependent transcytosis, increased tropism for placental cell types that are more permissive to virus infections, and maternal immune-mediated damage to the syncytiotrophoblast layer, thus allowing for breaches in the placental barrier. Alternatively, herpes simplex virus may spread from the ascending intravaginal route to infect the fetus, thereby bypassing the syncytiotrophoblast layer altogether.

Figure 2.10 Transplacental virus infections. Several viruses, including Zika virus, rubella virus, cytomegalovirus, and herpes simplex virus, can cross from mother to fetus. How these vertically transmitted infections might occur is dependent on multiple variables including virus type and fetal age. Syncytiotrophoblasts are crucial cells that lie at the maternal-fetal interface and are resistant to infection by many viruses. Routes of vertical transmission across the placenta could include breaks in the syncytial cell layer, targeting other cell types such as cytotrophoblasts or extravillous trophoblasts, or bypassing this by mechanisms such as direct antibody-mediated transcytosis.

Although the portals described above are all anatomical “gateways” by which viruses (and other pathogens) may cross barriers to initiate an infection, human cognition and intuition may also influence the viral pathogens to which we may be exposed (Box 2.6).