Inhibition of autophagy limits vertical transmission of Zika virus in pregnant mice
Bin Cao et al., J Exp Med. (2017) 214:2303-2313
 

Speaker: Hsiao-Jung Chiu (邱筱容)                Time: 15:10～16:00, May. 16, 2018

Commentator: Dr. Hsiao-Sheng Liu (劉校生 教授)   Place: Room 601

Abstract:

　　Zika virus (ZIKV) is a global emerging mosquito-transmitted flavivirus. ZIKV infection was known to cause self-limiting illness characterized by rash, myalgia, conjunctivitis, and headache. Besides the syndromes above, recent studies show that maternal infection during pregnancy may lead to placental insufficiency, fetal demise, microcephaly, and other congenital malformations in fetuses and new born infants [1]. With a broad cell tropism which includes villous placental trophoblasts and other cells in placenta [2], ZIKV is thought to be able to disseminate into the intrauterine space and infect the fetus. The placenta, which forms a barrier between maternal and fetus, uses autophagy mechanism to protect fetus from maternal-fetal transmission of pathogens. However, some pathogens have evolve mechanisms to evade, inhibit or hijack the autophagy machinery to facilitate infection and survival [3]. To determine the effects of autophagy on ZIKV infection in placenta and its impact on vertical transmission, authors perform ZIKV infection in both human trophoblasts and pregnant mice. Result show that ZIKV infection activates autophagic activities in human trophoblasts and in the mouse placenta. On the other hand, inhibition of autophagy pathway in human trophoblasts and autophagy essential gene Atg16l1 in mice reduces ZIKV infection in placentas and fetuses, and resulted in improved fetal outcomes. Collectively, these results suggest that inhibition of autophagy might be a choice to treat ZIKV-infected pregnant patients. Thus, authors test the effect of hydroxychloroquine (HCQ), an autophagy inhibitor which has approved for use in pregnant women, in pregnant mice. Consistent with the above findings, HCQ reduces ZIKV vertical transmission and attenuates the damages caused by ZIKV infection in both maternal placenta and fetus.                

References:

1. Chibueze EC. et al., Reprod Health. (2017) 14:28
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   Miner et al., Cell (2016) 165:1081-1091; Quicke et al., Cell Host Microbe. (2016) 20:83-90; Tabata et al., Cell Host Microbe. (2016) 20:155-166 2016; Aagaard KM et al., Sci Rep. (2017) 7:41389
3. Cemma M et al., Curr Biol. (2012) 22:R540-5.