Rearrangement of Actin Cytoskeleton by Zika Virus Infection Facilitates Blood–Testis Barrier Hyperpermeability

Abstract

In recent years, various serious diseases caused by Zika virus (ZIKV) have made it impossible to be ignored. Confirmed existence of ZIKV in semen and sexually transmission of ZIKV suggested that it can break the blood–testis barrier (BTB), or Sertoli cell barrier (SCB). However, little is known about the underlying mechanism. In this study, interaction between actin, an important component of the SCB, and ZIKV envelope (E) protein domain III (EDIII) was inferred from co-immunoprecipitation (Co-IP) liquid chromatography–tandem mass spectrometry (LC–MS/MS) analysis. Confocal microscopy confirmed the role of actin filaments (F-actin) in ZIKV infection, during which part of the stress fibers, the bundles that constituted by paralleled actin filaments, were disrupted and presented in the cell periphery. Colocalization of E and reorganized actin filaments in the cell periphery of transfected Sertoli cells suggests a participation of ZIKV E protein in ZIKV-induced F-actin rearrangement. Perturbation of F-actin by cytochalasin D (CytoD) or Jasplakinolide (Jas) enhanced the infection of ZIKV. More importantly, the transepithelial electrical resistance (TEER) of an in vitro mouse SCB (mSCB) model declined with the progression of ZIKV infection or overexpression of E protein. Co-IP and confocal microscopy analyses revealed that the interaction between F-actin and tight junction protein ZO-1 was reduced after ZIKV infection or E protein overexpression, highlighting the role of E protein in ZIKV-induced disruption of the BTB. We conclude that the interaction between ZIKV E and F-actin leads to the reorganization of F-actin network, thereby compromising BTB integrity.

Bibliometric and visual analysis of blood-testis barrier research

“…Although these viruses cannot directly cross the BTB, the inflammatory factors they secrete can cause the TJ proteins between supporting cells to degrade, disrupting the structure and function of the BTB and allowing viruses to invade the spermatogenic tubules. The interaction of ZIKV E with F-actin causes the F-actin network to reorganize, jeopardizing BTB integrity ( Nie et al, 2021 ). When Sertoli cells are exposed to inflammatory mediators originating from ZIKV-infected macrophages, the ZO-1 protein is degraded, which is associated with enhanced BTB permeability ( Siemann et al, 2017 ).…”

“…To analyze the citations of the documents, cocitation analysis of the cited references was performed (Figure 5B; Table 5). There were a total of 40,575 cited references; the most highly cited references were Cheng C. Yan (Cheng and Mruk, 2012), Mruk DD (Mruk and Cheng, 2004), Vogl AW (Vogl et al, 2008), Meng J (Meng et al, 2005), Cheng C. Yan (Cheng and Mruk, 2002), Cheng C. Yan (Cheng and Mruk, 2010), Yan HHN (Yan et al, 2008), Mazk DD (Yan et al, 2008), O'donnell Liza (O'Donnell et al, 2011), and Pelletier RM (Pelletier, 2011).…”

Zika Virus Infection of Sertoli Cells Alters Protein Expression Involved in Activated Immune and Antiviral Response Pathways, Carbohydrate Metabolism and Cardiovascular Disease

“…Sertoli cells have reported the roles of a particular protein [70] or its impact on the BTB [71]. However, this is the first study that uses mass spectrometry to understand global proteomic alterations induced by ZIKV infection in HSerC at 3, 5 and 7 dpi.…”

RNA-Seq analysis of duck embryo fibroblast cells gene expression during duck Tembusu virus infection

“…To accomplish viral replication, assembly, and maturation, intracellular complexes of the virus utilize intracellular cytoskeletal components of the host to move from the periphery of the cell to sites of RNA synthesis [ 30 ]. Microtubules and actin are important components of the cellular cytoskeleton that facilitates flavivirus intracellular translocation to the nucleus [ 31 – 33 ]. In our study, we observed that DTMUV-infected DEF included a number of upregulated DEG that regulate the action cytoskeleton signaling pathway, such as FGF (fibroblast growth factor) family members (FGF1/3/4/5/19) and scaffold protein IQGAP2, which play a role in stabilizing microtubules [ 34 – 36 ] (Figure 6 ).…”