Human placental trophoblasts confer viral resistance to recipient cells

Delorme-Axford, Elizabeth; Donker, Rogier B.; Mouillet, Jean-François; Chu, Tianjiao; Bayer, Avraham; Ouyang, Yi‐Bing; Wang, Tianyi; Stolz, Donna B.; Sarkar, Saumendra N.; Morelli, Adrián E.; Sadovsky, Yoel; Coyne, Carolyn B.

doi:10.1073/pnas.1304718110

Cited by 425 publications

(453 citation statements)

References 51 publications

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“…PHTu and PHTd from term placentas are highly resistant to infection by viruses, including the flaviviruses ZIKV and DENV (23,24), an observation consistent with the high expression of a full range of viral defense genes described above. Here we describe the effects of two strains of ZIKV-the African Lineage strain MR766 (ZIKV U ) (50) and the Asian Lineage strain Cambodia FSS13025 (ZIKV C ) (51)-on ESCu and on ESC after their differentiation to trophoblast (ESCd).…”

Section: Relative Susceptibilities Of Esc and Esc-derived Trophoblastsupporting

confidence: 79%

“…Cultures of primary term human placental cytotrophoblast (CTB) recovered and allowed to differentiate into STB in vitro are resistant to infection by a range of diverse viruses, including vesicular stomatitis virus (Rhabdoviridae; Vesiculovirus), poliovirus (Picornaviridae; Enterovirus; enterovirus C), vaccinia virus (Poxviridae; Chordopoxvirinae; Orthopoxvirus), human cytomegalovirus (Herpesviridae; Betaherpesvirinae; Cytomegalovirus) (23), and, as shown more recently, to two strains of ZIKV and DENV2 (Flaviviridae; Flavivirus) (24). Whether placental STB from earlier in gestation is comparably resistant to ZIKV and related viruses remains unclear.…”

Section: Significancementioning

confidence: 99%

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Vulnerability of primitive human placental trophoblast to Zika virus

Sheridan

Yunusov

Balaraman

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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157

155

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Infection of pregnant women by Asian lineage strains of Zika virus (ZIKV) has been linked to brain abnormalities in their infants, yet it is uncertain when during pregnancy the human conceptus is most vulnerable to the virus. We have examined two models to study susceptibility of human placental trophoblast to ZIKV: cytotrophoblast and syncytiotrophoblast derived from placental villi at term and colonies of trophoblast differentiated from embryonic stem cells (ESC). The latter appear to be analogous to the primitive placenta formed during implantation. The cells from term placentas, which resist infection, do not express genes encoding most attachment factors implicated in ZIKV entry but do express many genes associated with antiviral defense. By contrast, the ESC-derived trophoblasts possess a wide range of attachment factors for ZIKV entry and lack components of a robust antiviral response system. These cells, particularly areas of syncytiotrophoblast within the colonies, quickly become infected, produce infectious virus and undergo lysis within 48 h after exposure to low titers (multiplicity of infection > 0.07) of an African lineage strain (MR766 Uganda: ZIKVU) considered to be benign with regards to effects on fetal development. Unexpectedly, lytic effects required significantly higher titers of the presumed more virulent FSS13025 Cambodia (ZIKVC). Our data suggest that the developing fetus might be most vulnerable to ZIKV early in the first trimester before a protective zone of mature villous trophoblast has been established. Additionally, MR766 is highly trophic toward primitive trophoblast, which may put the early conceptus of an infected mother at high risk for destruction.

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Section: Relative Susceptibilities Of Esc and Esc-derived Trophoblastsupporting

confidence: 79%

Section: Significancementioning

confidence: 99%

Vulnerability of primitive human placental trophoblast to Zika virus

Sheridan

Yunusov

Balaraman

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

157

155

View full text Add to dashboard Cite

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“…This has been demonstrated for trophoblasts, which are largely resistant to infection by various viruses, including HIV, probably contributing to in vivo fetus protection. EVs produced by these cells in vitro carry host miRNAs and deliver them to virus-susceptible cells, making them resistant to virus infection (62).…”

Section: To Be or Not To Be Infected: Evs In Pro-and Antiviral Stratementioning

confidence: 99%

Extracellular vesicles and viruses: Are they close relatives?

Hoen

Cremer

Gallo

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

425

390

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Extracellular vesicles (EVs) released by various cells are small phospholipid membrane-enclosed entities that can carry miRNA. They are now central to research in many fields of biology because they seem to constitute a new system of cell–cell communication. Physical and chemical characteristics of many EVs, as well as their biogenesis pathways, resemble those of retroviruses. Moreover, EVs generated by virus-infected cells can incorporate viral proteins and fragments of viral RNA, being thus indistinguishable from defective (noninfectious) retroviruses. EVs, depending on the proteins and genetic material incorporated in them, play a significant role in viral infection, both facilitating and suppressing it. Deciphering the mechanisms of EV-cell interactions may facilitate the design of EVs that inhibit viral infection and can be used as vehicles for targeted drug delivery.

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“…Much akin to miRNAs, exosomes were traditionally believed to be a mechanism of cellular waste/disposal transport, but miRNAs, specifically C19MC, are abundantly released from primary human trophoblasts. 111 Exosomes containing the C19MC miRNA cluster infer viral resistance to recipient cells through autophagy, 113 and may help immunologically protect the developing fetus. These recent studies illustrate that exosomes may play an important role in maternal-fetal exchange, 111,114 as well as in embryo implantation through maternal-fetal cross-talk.…”

Section: Microrna Regulation In the Placentamentioning

confidence: 99%

MicroRNAs, immune cells and pregnancy

et al. 2014

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MicroRNAs (miRNAs) are a recently discovered class of non-coding RNAs that are expressed in many cell types, where they regulate the expression of complementary RNAs, thus modulating the stability and translation of mRNAs. miRNAs are predicted to regulate the expression of ,50% of all protein coding genes in mammals. Therefore, they participate in virtually all cellular processes investigated so far. Altered miRNAs expressions are associated with both physiological (pregnancy) and pathological processes (cancer). As the dynamic maternal-fetal interface plays a critical role in the maintenance of successful pregnancy, it is not surprising that the miRNAs that are unique to reproductive tissues are abundantly expressed. Research in this field has demonstrated the presence and dysregulation of a distinct set of pregnancy-associated miRNAs; however, most studies have centered on localizing various miRNAs in reproductive microdomains associated with normal or complicated pregnancies. Although several independent miRNA regulatory mechanisms associated with endometrial receptivity, immune cells, angiogenesis and placental development have been studied, miRNA-mediated regulation of pregnancy remains poorly understood. This review provides a summary of the current data on miRNA regulation as well as functional profiles of miRNAs that are found in the uterus, in immune cells associated with maternal tolerance to the fetus, and those involved in angiogenesis and placental development.

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Human placental trophoblasts confer viral resistance to recipient cells

Cited by 425 publications

References 51 publications

Vulnerability of primitive human placental trophoblast to Zika virus

Vulnerability of primitive human placental trophoblast to Zika virus

Extracellular vesicles and viruses: Are they close relatives?

MicroRNAs, immune cells and pregnancy

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