**Zika Virus Infects Human Placental Mast Cells and the HMC-1 Cell Line, and Triggers Degranulation, Cytokine Release and Ultrastructural Changes**

**Kíssila Rabelo 1,\*, Antônio José da Silva Gonçalves 2, Luiz José de Souza 3, Anna Paula Sales 3, Sheila Maria Barbosa de Lima 4, Gisela Freitas Trindade 4, Bianca Torres Ciambarella 1, Natália Recardo Amorim Tasmo 5, Bruno Lourenço Diaz 5, Jorge José de Carvalho 1, Márcia Pereira de Oliveira Duarte 2,\* and Marciano Viana Paes 2,\***


Received: 6 March 2020; Accepted: 5 April 2020; Published: 16 April 2020

**Abstract:** Zika virus (ZIKV) is an emergen<sup>t</sup> arthropod-borne virus whose outbreak in Brazil has brought major public health problems. Infected individuals have different symptoms, including rash and pruritus, which can be relieved by the administration of antiallergics. In the case of pregnan<sup>t</sup> women, ZIKV can cross the placenta and infect the fetus leading to congenital defects. We have identified that mast cells in the placentae of patients who had Zika during pregnancy can be infected. This led to our investigation on the possible role of mast cells during a ZIKV infection, using the HMC-1 cell line. We analyzed their permissiveness to infection, release of mediators and ultrastructural changes. Flow cytometry detection of ZIKV-NS1 expression 24 h post infection in 45.3% of cells showed that HMC-1 cells are permissive to ZIKV infection. Following infection, β-hexosaminidase was measured in the supernatant of the cells with a notable release at 30 min. In addition, an increase in TNF-<sup>α</sup>, IL-6, IL-10 and VEGF levels were measured at 6 h and 24 h post infection. Lastly, different intracellular changes were observed in an ultrastructural analysis of infected cells. Our findings sugges<sup>t</sup> that mast cells may represent an important source of mediators that can activate other immune cell types during a ZIKV infection, which has the potential to be a major contributor in the spread of the virus in cases of vertical transmission.

**Keywords:** flavivirus; immune response; inflammatory mediator
