Abstract
Previous work showed that the thymus can be infected by RNA viruses as HIV and HTLV-1. We thus hypothesized that the thymus might also be infected by the Zika virus (ZIKV). Herein we provide compelling evidence that ZIKV targets human thymic epithelial cells (TEC) in vivo and in vitro. ZIKV-infection enhances keratinization of TEC, with a decrease in proliferation and increase in cell death. Moreover, ZIKV modulates a high amount of coding RNAs with upregulation of genes related to cell adhesion and migration, as well as non-coding genes including miRNAs, circRNAs and lncRNAs. Moreover, we observed enhanced attachment of lymphoblastic T-cells to infected TEC, as well as virus transfer to those cells. Lastly, alterations in thymuses from babies congenitally infected were seen, with the presence of viral envelope protein in TEC. Taken together, our data reveals that the thymus, particularly the thymic epithelium, is a target for the ZIKV with changes in the expression of molecules that are relevant for interactions with developing thymocytes.
Highlights
Zika virus (ZIKV) epidemics in 2015-2016 resulted in devastating effects, causing microcephaly, other related congenital defects at birth and neurodevelopmental delay after two years in children born from mothers infected by the virus during pregnancy[1,2,3,4]
The behavior of the human immune system secondary to a congenital syndrome caused by the ZIKV remains largely unknown, there is evidence that innate and acquired immune cells can be infected by the virus, as ascertained by studies on peripheral blood leukocytes[21,22]
We tackled this issue by investigating whether or not the human thymic epithelium could be infected by ZIKV
Summary
Zika virus (ZIKV) epidemics in 2015-2016 resulted in devastating effects, causing microcephaly, other related congenital defects at birth and neurodevelopmental delay after two years in children born from mothers infected by the virus during pregnancy[1,2,3,4]. Much less is known on the putative infection of primary lymphoid organs, and more in the thymus This central lymphoid organ is responsible for the generation of T lymphocytes under the control of the thymic microenvironment, a three-dimensional cellular network mainly composed by thymic epithelial cells – TEC11. In this respect, it is interesting to note the thymus as a target organ for other RNA viruses, such as HIV12 and HTLV-113,14. Data are provided showing that ZIKV-infection enhances keratinization of TEC, with a decrease in proliferation and increase in cell death. Our data reveal that the thymus is a target for the ZIKV and may function as a reservoir of the virus during congenital infection
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