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Differential Expression of Rab5 and Rab7 Small GTPase Proteins in Placental Tissues From Pregnancies Affected by Maternal Coronavirus Disease 2019.
Benarroch, Yoel; Juttukonda, Lillian; Sabharwal, Vishakha; Boateng, Jeffery; Khan, Amir R; Yarrington, Christina; Wachman, Elisha M; Taglauer, Elizabeth.
  • Benarroch Y; Boston University School of Medicine, Boston, MA, USA.
  • Juttukonda L; Boston Combined Residency Program in Pediatrics, Boston Medical Center and Children's Hospital Boston, Boston, MA, USA.
  • Sabharwal V; Department of Pediatrics, Boston Medical Center, Boston, MA, USA.
  • Boateng J; Department of Pediatrics, Boston Medical Center, Boston, MA, USA.
  • Khan AR; Division of Newborn Medicine, Department of Pediatrics, Boston Children's Hospital, Boston, MA, USA; School of Biochemistry and Immunology, Trinity College, Dublin, Ireland.
  • Yarrington C; Department of Obstetrics and Gynecology, Boston Medical Center, Boston, MA, USA.
  • Wachman EM; Department of Pediatrics, Boston Medical Center, Boston, MA, USA.
  • Taglauer E; Department of Pediatrics, Boston Medical Center, Boston, MA, USA; Division of Newborn Medicine, Department of Pediatrics, Boston Children's Hospital, Boston, MA, USA. Electronic address: Elizabeth.Taglauer@bmc.org.
Clin Ther ; 43(2): 308-318, 2021 02.
Article in English | MEDLINE | ID: covidwho-1064961
ABSTRACT

PURPOSE:

The majority of pregnancies affected by maternal coronavirus disease 2019 (COVID-19) do not result in fetal transmission. However, several studies have identified parenchymal changes in their placental tissues, suggesting a placental response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at the maternal-fetal interface. Although many COVID-19 placental studies have focused on the expression of the canonical SARS-CoV-2 entry proteins angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2, further characterization of subcellular molecules involved in viral trafficking have not yet been investigated in these tissues. Of interest are Rab proteins, a family of small GTPase proteins that direct intracellular transport between different endocytic organelles. Rab5 and Rab7 in particular have previously been implicated in HIV and cytomegalovirus invasion of placental trophoblast cells in vitro; the localization of these molecules has not been fully characterized within the human maternal-fetal interface, however, or within placental tissues from SARS-CoV-2-infected pregnancies.

METHODS:

Using fluorescent immunohistochemistry, Rab5 and Rab7 placental localization and comparative fluorescence intensity were explored in a cohort of placental tissues from pregnancies affected by maternal COVID-19 disease (COVID, n = 15) compared with contemporary control subjects (Control, n = 10). Fluorescence intensity was quantified by using corrected total cell fluorescence values.

FINDINGS:

Within placental villi, Rab5 was consistently localized in syncytiotrophoblast and cytotrophoblast cells. Rab5 had significantly higher mean (SEM) fluorescence intensity in the COVID cohort (Control, 1.96 [0.16]; COVID, 2.62 [0.09]; P = 0.0014). In contrast, although Rab7 was also localized within placental villous syncytiotrophoblast and cytotrophoblast cells, mean (SEM) Rab7 fluorescence intensity was significantly downregulated in COVID vs Control placentas (Control, 35.9 [4.1]; COVID, 20.1 [0.52]; P = 0.0001). IMPLICATIONS This differential expression of Rab5 and Rab7 suggests that placental endocytic pathways may be altered at the maternal-fetal interface in pregnancies affected by maternal SARS-CoV-2 infection. As key molecules governing intracellular vesicle transport, including viral trafficking, Rab GTPase proteins may be of interest for ongoing studies examining placental responses to COVID-19 in pregnancy.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Placenta / Pregnancy Complications, Infectious / Trophoblasts / Rab GTP-Binding Proteins / Rab5 GTP-Binding Proteins / COVID-19 Type of study: Cohort study / Observational study / Prognostic study Limits: Female / Humans / Pregnancy Language: English Journal: Clin Ther Year: 2021 Document Type: Article Affiliation country: J.clinthera.2021.01.002

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Placenta / Pregnancy Complications, Infectious / Trophoblasts / Rab GTP-Binding Proteins / Rab5 GTP-Binding Proteins / COVID-19 Type of study: Cohort study / Observational study / Prognostic study Limits: Female / Humans / Pregnancy Language: English Journal: Clin Ther Year: 2021 Document Type: Article Affiliation country: J.clinthera.2021.01.002