Placental Mechanics in the Zika-Microcephaly Relationship

Abstract

How the Zika virus (ZIKV) accesses the embryo remains unknown. In this issue, Quicke et al. (2016) use an in vitro model of the human placenta to show that placental macrophages are more permissive to ZIKV infection than trophoblasts, which may be refractory to infection (Bayer et al., 2016).

Experimental Zika Virus Infection in the Pregnant Common Marmoset Induces Spontaneous Fetal Loss and Neurodevelopmental Abnormalities

“…Here we observed extensive ZIKV infection of the placenta and fetus in the absence of overt inflammation and despite induction of a robust host antiviral response. This is consistent with ours and others recently described human placental pathogenesis [35][36][37][38][55][56][57] .…”

“…However, there is clear evidence of injury to the fetal neocortex as visualized by histopathological examination showing neuronal organization, mimicking findings in mice models of ZIKV vertical transmission as well as human cases 7,38 . This notion of the significance of placental mechanics and placental cell infection in the pathogenesis in CZS has been previously brought forward by a number of investigators 29,35,37,39,40,[55][56][57] . It has long been supposed that shuttling of bloodborne ZIKV to the developing human fetus requires establishment of maternal blood in the intervillous space, which occurs approximately at 6-8 weeks post-conception (mean of roughly 42 days) ( Fig.…”

“…8). We speculate that the capacity for the marmoset to better recapitulate human infection is related to ongoing placental development and trophoblast renewal, whereby the virus is permissive to replication in both placental trophoblasts 35 and placental macrophages (Hofbauer cells) 36 without evidence of inflammation [35][36][37][38][55][56][57] . As is likely the case in humans, the placenta may be viewed as an effective "shuttle" to the fetus, functioning first as a reservoir and later as a source of fetal infection of susceptible cell types and tissues, including neuroprogenitor cells 37 .…”

“…For both ZIKV-infected marmosets and humans, fetal infection appears to be established in the absence of localized fetal and placental inflammation [35][36][37][38][55][56][57] . However, there is clear evidence of injury to the fetal neocortex as visualized by histopathological examination showing neuronal organization, mimicking findings in mice models of ZIKV vertical transmission as well as human cases 7,38 .…”

The Role of Secretory Autophagy in Zika Virus Transfer through the Placental Barrier

“…For example, both type I interferons and type III interferons are induced by Zika virus infections (Bayer et al, 2016; Quicke et al, 2016), and interferon-λ restricts Zika virus replication in human trophoblast cells (Bayer et al, 2016). Although, interferons and associated cytokines may generate indirect teratogenic and/or neurotoxic effects to the fetus (Adibi et al, 2016b; Mor, 2016), interferon-α does not apparently increase the risk of miscarriage, major malformation, preterm delivery, or stillbirth (Yazdani Brojeni et al, 2012). Moreover, interferon-α may show some protective effects against pregnancy loss in the case of essential thrombocythemia (Yazdani Brojeni et al, 2012).…”