Roles of TGF-β1 in Viral Infection during Pregnancy: Research Update and Perspectives

Abstract

Transforming growth factor-beta 1 (TGF-β1) is a pleiotropic growth factor playing various roles in the human body including cell growth and development. More functions of TGF-β1 have been discovered, especially its roles in viral infection. TGF-β1 is abundant at the maternal-fetal interface during pregnancy and plays an important function in immune tolerance, an essential key factor for pregnancy success. It plays some critical roles in viral infection in pregnancy, such as its effects on the infection and replication of human cytomegalovirus in syncytiotrophoblasts. Interestingly, its role in the enhancement of Zika virus (ZIKV) infection and replication in first-trimester trophoblasts has recently been reported. The above up-to-date findings have opened one of the promising approaches to studying the mechanisms of viral infection during pregnancy with links to corresponding congenital syndromes. In this article, we review our current and recent advances in understanding the roles of TGF-β1 in viral infection. Our discussion focuses on viral infection during pregnancy, especially in the first trimester. We highlight the mutual roles of viral infection and TGF-β1 in specific contexts and possible functions of the Smad pathway in viral infection, with a special note on ZIKV infection. In addition, we discuss promising approaches to performing further studies on this topic.

Keywords: HIV; SARS-CoV-2; TGF-β1; ToRCH; Zika; influenza; pregnancy; rubella; transforming growth factor; virus.

Figure 1

Viral transmission to pregnant mother and her fetus/baby. (A) Transmission routes to pregnant mother. (B) Vertical transmission routes. (C) Intrauterine transmission-possible mechanisms of virus invasion into the placenta barrier. Abbreviations: RuV, rubella virus; HCMV, human cytomegalovirus; HIV, human immunodeficiency virus; HBV, hepatitis B virus; HSV, herpes simplex virus; IAV, influenza A virus; ZIKV, Zika virus; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; CBT, cytotrophoblast; STB, syncytiotrophoblast; EVT, extravillous trophoblast; EC, endothelial cells; T reg, regulatory T cells.

Figure 2

Trophoblasts, microvillous structure and the published effects of TGF-β1 on viral infection in trophoblasts at the maternal–fetal interface. ❶, TGF-β1 increases the infection and replication of HCMV in STBs through macrophage contact [26]; ❷, enhancement of ZIKV infection and replication in trophoblasts by TGF-β1 [34]; ❸, no effect on HIV construct replication in trophoblasts under TGF-β1 treatment [257]; ❹, increases HBx-transfected trophoblast proliferation and invasion [258]. Abbreviations: HCMV, human cytomegalovirus; HBV, hepatitis B virus; HIV, human immunodeficiency virus; ZIKV, Zika virus; CBT, cytotrophoblast; STB, syncytiotrophoblast; EVT, extravillous trophoblast; T reg, regulatory T cells.

Figure 3

The Smad pathway and possible underlying mechanisms of the published effects of TGF-β1 on ZIKV infection in relation to the virus life cycle.