Zika virus tropism during early infection of the testicular interstitium and its role in viral pathogenesis in the testes

ABSTRACTZika virus (ZIKV) is a positive-sense RNA flavivirus and can cause serious neurological disorders including microcephaly in infected fetus. As a mosquito-borne arbovirus, ZIKV enters bloodstream and is transmitted into the fetus through the placenta in pregnant women. Monocytes are considered one of the earliest blood cell types to be infected by ZIKV. As a first line defence, monocytes are crucial components in innate immunity and host responses and may impact viral pathogenesis in humans. Previous studies have shown that ZIKV infection can activate inflammasomes and induce proinflammatory cytokines in monocytes. In this report, we showed that ZIKV carried out a productive infection, which lead to cell death in human and murine monocytic cells. In addition to the presence of cleaved caspase-3, indicating that apoptosis was involved, we identified the cleaved caspase-1 and gasdemin D (GSDMD) as well as increased secretion of IL-1β and IL-18, suggesting that the inflammasome was activated that may lead to pyroptosis in infected monocytes. The pyroptosis was NLRP3-dependent and could be suppressed in the monocytes treated with shRNA to target and knockdown caspase-1, or an inhibited for caspase-1, indicating that the pyroptosis was triggered via a canonical approach. Our findings in this study demonstrate a concomitant occurrence of apoptosis and pyroptosis in ZIKV-infected monocytes, with multiple mechanisms involved in the cell death, which may have potentially significant impacts on viral pathogenesis in humans.

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Faculty Opinions recommendation of Zika virus tropism and interactions in myelinating neural cell cultures: CNS cells and myelin are preferentially affected.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.727746944.793534307 ◽

2017 ◽

Author(s):

David Rowitch

Keyword(s):

Cell Cultures ◽

Zika Virus ◽

Neural Cell ◽

Virus Tropism

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Zika virus tropism and interactions in myelinating neural cell cultures: CNS cells and myelin are preferentially affected

Acta Neuropathologica Communications ◽

10.1186/s40478-017-0450-8 ◽

2017 ◽

Vol 5 (1) ◽

Cited By ~ 22

Author(s):

Stephanie L. Cumberworth ◽

Jennifer A. Barrie ◽

Madeleine E. Cunningham ◽

Daniely Paulino Gomes de Figueiredo ◽

Verena Schultz ◽

...

Keyword(s):

Cell Cultures ◽

Zika Virus ◽

Neural Cell ◽

Virus Tropism

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Neuroimmune Evasion of Zika Virus to Facilitate Viral Pathogenesis

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2021.662447 ◽

2021 ◽

Vol 11 ◽

Author(s):

Xiaochun Xie ◽

Jianxiong Zeng

Keyword(s):

Immune Responses ◽

Immune Evasion ◽

Zika Virus ◽

Congenital Malformations ◽

Viral Pathogenesis ◽

Embryonic Brain ◽

Zikv Infection ◽

Stem And Progenitor Cells ◽

Developmental Impairment ◽

Effective Drugs

Zika virus (ZIKV), which preferentially targets neural stem and progenitor cells (NSCs) especially in developing brain, is causally associated with fetal microcephaly, intrauterine retardation, and other congenital malformations in humans. However, there are, so far, no effective drugs and vaccines against ZIKV epidemics, warranting an enhanced understanding of ZIKV biology. Immune response is essential for neuronal cells to combat viral invasion. In turn, neurotropic ZIKV has developed a complex strategy of neuroimmune evasion to facilitate viral pathogenesis, especially developmental impairment in embryonic brain. Here, we review not only overall knowledge of ZIKV-related immune responses, but also current advances in our understanding of immune evasion in ZIKV infection. We also review several specific mechanisms underlying ZIKV protein-mediated immune evasion for viral pathogenesis.

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