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

2021 ◽  
Author(s):  
Yiwen Nie ◽  
Lixia Hui ◽  
Moujian Guo ◽  
Wei Yang ◽  
Rui Huang ◽  
...  
Keyword(s):  
Confocal Microscopy ◽  
Zika Virus ◽  
Actin Filaments ◽  
Protein Domain ◽  
Cell Periphery ◽  
Zikv Infection ◽  
E Protein ◽  
Junction Protein ◽  
Blood Testis Barrier

AbstractIn 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.

scholarly journals Autophagy in Zika Virus Infection: A Possible Therapeutic Target to Counteract Viral Replication

2019 ◽  
Vol 20 (5) ◽  
pp. 1048 ◽  
Author(s):  
Rossella Gratton ◽  
Almerinda Agrelli ◽  
Paola Tricarico ◽  
Lucas Brandão ◽  
Sergio Crovella
Keyword(s):  
Public Health ◽  
Viral Replication ◽  
Zika Virus ◽  
Health Concern ◽  
Mtor Signaling Pathway ◽  
Catabolic Pathway ◽  
Public Health Concern ◽  
Zikv Infection ◽  
Fundamental Process

Zika virus (ZIKV) still constitutes a public health concern, however, no vaccines or therapies are currently approved for treatment. A fundamental process involved in ZIKV infection is autophagy, a cellular catabolic pathway delivering cytoplasmic cargo to the lysosome for degradation—considered as a primordial form of innate immunity against invading microorganisms. ZIKV is thought to inhibit the Akt-mTOR signaling pathway, which causes aberrant activation of autophagy promoting viral replication and propagation. It is therefore appealing to study the role of autophagic molecular effectors during viral infection to identify potential targets for anti-ZIKV therapeutic intervention.

scholarly journals Immunogenicity and Efficacy of Zika Virus Envelope Domain III in DNA, Protein, and ChAdOx1 Adenoviral-Vectored Vaccines

Vaccines ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 307 ◽  
Author(s):  
César López-Camacho ◽  
Giuditta De Lorenzo ◽  
Jose Luis Slon-Campos ◽  
Stuart Dowall ◽  
Peter Abbink ◽  
...  
Keyword(s):  
Immune Responses ◽  
Dengue Virus ◽  
Zika Virus ◽  
Neutralizing Antibodies ◽  
Vaccine Candidate ◽  
Protein Domain ◽  
Virus Envelope ◽  
Zikv Infection ◽  
Domain Iii ◽  
Open Question

The flavivirus envelope protein domain III (EDIII) was an effective immunogen against dengue virus (DENV) and other related flaviviruses. Whether this can be applied to the Zika virus (ZIKV) vaccinology remains an open question. Here, we tested the efficacy of ZIKV-EDIII against ZIKV infection, using several vaccine platforms that present the antigen in various ways. We provide data demonstrating that mice vaccinated with a ZIKV-EDIII as DNA or protein-based vaccines failed to raise fully neutralizing antibodies and did not control viremia, following a ZIKV challenge, despite eliciting robust antibody responses. Furthermore, we showed that ZIKV-EDIII encoded in replication-deficient Chimpanzee adenovirus (ChAdOx1-EDIII) elicited anti-ZIKV envelope antibodies in vaccinated mice but also provided limited protection against ZIKV in two physiologically different mouse challenge models. Taken together, our data indicate that contrary to what was shown for other flaviviruses like the dengue virus, which has close similarities with ZIKV-EDIII, this antigen might not be a suitable vaccine candidate for the correct induction of protective immune responses against ZIKV.

scholarly journals High-throughput fitness profiling of Zika virus E protein reveals different roles for N-linked glycosylation during infection of mammalian and mosquito cells

2017 ◽  
Author(s):  
Danyang Gong ◽  
Tian-hao Zhang ◽  
Dawei Zhao ◽  
Yushen Du ◽  
Travis J. Chapa ◽  
...  
Keyword(s):  
Zika Virus ◽  
Cell Receptor ◽  
Human Cells ◽  
Nucleotide Position ◽  
List Type ◽  
Zikv Infection ◽  
E Protein ◽  
Mosquito Cells ◽  
Viral Mutant ◽  
Replication Fitness

AbstractZika virus (ZIKV) infection causes Guillain-Barré syndrome and severe birth defects. ZIKV envelope (E) protein is the major viral protein involved in cell receptor binding and entry and therefore considered one of the major determinants in ZIKV pathogenesis. Here, we report a gene-wide mapping of functional residues of ZIKV E protein using a mutant library with changes covering every nucleotide position. By comparing the replication fitness of every viral mutant between mosquito and human cells, we identified that mutations affecting N-linked glycosylation at N154 position display the most divergence. Through characterizing individual mutants, we show that, while ablation of N-linked glycosylation selectively benefits ZIKV infection of mosquito cells by enhancing cell entry, it either had little impact on ZIKV infection on certain human cells or decreased infection through entry factor DC-SIGN. In conclusion, we define the roles of individual residues of ZIKV envelope protein, which contribute to ZIKV replication fitness in human and mosquito cells.HighlightsGene-wide mapping of functional residues of E protein in human and mosquito cells.Mutations affecting N-linked glycosylation display the most dramatic difference.N-linked glycosylation decreases ZIKV entry into mosquito cells.N-linked glycosylation is important for DC-SIGN mediated infection of human cells.

scholarly journals Syncytiotrophoblast of Placentae from Women with Zika Virus Infection Has Altered Tight Junction Protein Expression and Increased Paracellular Permeability

Cells ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 1174 ◽  
Author(s):  
Jael Miranda ◽  
Dolores Martín-Tapia ◽  
Yolotzin Valdespino-Vázquez ◽  
Lourdes Alarcón ◽  
Aurora Espejel-Nuñez ◽  
...  
Keyword(s):  
Zika Virus ◽  
Maternal Blood ◽  
Paracellular Permeability ◽  
Ruthenium Red ◽  
Paracellular Pathway ◽  
Zikv Infection ◽  
Chorionic Villi ◽  
Intervillous Space ◽  
Junction Protein ◽  
Trophoblast Cell Line

The cytotrophoblast of human placenta transitions into an outer multinucleated syncytiotrophoblast (STB) layer that covers chorionic villi which are in contact with maternal blood in the intervillous space. During pregnancy, the Zika virus (ZIKV) poses a serious prenatal threat. STB cells are resistant to ZIKV infections, yet placental cells within the mesenchyme of chorionic villi are targets of ZIKV infection. We seek to determine whether ZIKV can open the paracellular pathway of STB cells. This route is regulated by tight junctions (TJs) which are present in the uppermost portion of the lateral membranes of STB cells. We analyzed the paracellular permeability and expression of E-cadherin, occludin, JAMs –B and –C, claudins -1, -3, -4, -5 and -7, and ZO-1, and ZO-2 in the STB of placentae from ZIKV-infected and non-infected women. In ZIKV-infected placentae, the pattern of expression of TJ proteins was preserved, but the amount of claudin-4 diminished. Placentae from ZIKV-infected women were permeable to ruthenium red, and had chorionic villi with a higher mean diameter and Hofbauer hyperplasia. Finally, ZIKV added to the basolateral surface of a trophoblast cell line reduced the transepithelial electrical resistance. These results suggest that ZIKV can open the paracellular pathway of STB cells.

scholarly journals Dengue, chikungunya and zika virus coinfection: results of the national surveillance during the zika epidemic in Colombia

2019 ◽  
Vol 147 ◽  
Author(s):  
Marcela Mercado-Reyes ◽  
Jorge Acosta-Reyes ◽  
Edgar Navarro-Lechuga ◽  
Sherill Corchuelo ◽  
Angélica Rico ◽  
...  
Keyword(s):  
Polymerase Chain Reaction ◽  
Zika Virus ◽  
Medical Records ◽  
National Surveillance ◽  
Chain Reaction ◽  
Zikv Infection ◽  
Tissue Samples ◽  
Epidemiologic Surveillance ◽  
Polymerase Chain

AbstractOur objective was to determine the frequency of zika (ZIKV), chikungunya (CHIKV) and dengue (DENV) virus coinfection and describe the mortality cases that occurred during the epidemiologic surveillance of the ZIKV epidemic in Colombia. We analysed all cases of suspected ZIKV infection that were reported to the National Institute of Health (October 2015–December 2016). DENV, CHIKV and ZIKV RNA were detected in serum or tissue samples using polymerase chain reaction assay. Medical records of the fatal cases were reviewed. We identified that 23 871 samples were processed. The frequency of viral agents was 439 (1.84%) for DENV, 257 (1.07%) for CHIKV and 10118 (42.38%) for ZIKV. Thirty-four (0.14%) cases of coinfection were identified. The CHIKV–ZIKV coinfection was present in 28 cases (82.3%), DENV–CHIKV in three (8.8%) and DENV–ZIKV in three (8.8%). Seven (20.6%) coinfection cases were fatal (two DENV–CHIKV cases and five CHIKV–ZIKV cases). Two cases were foetal deaths and the others were related to neurological syndrome and sepsis. In conclusion, the frequency of arbovirus coinfection during epidemic of ZIKV was low, and CHIKV–ZIKV coinfection was the most common. Mortality was high among coinfection patients. The role of each virus in the mortality cases of coinfection warrants further studies.

scholarly journals An Update on Sexual Transmission of Zika Virus

Pathogens ◽  
2018 ◽  
Vol 7 (3) ◽  
pp. 66 ◽  
Author(s):  
Hercules Sakkas ◽  
Petros Bozidis ◽  
Xenofon Giannakopoulos ◽  
Nikolaos Sofikitis ◽  
Chrissanthy Papadopoulou
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Reproductive System ◽  
Zika Virus ◽  
Rna Virus ◽  
Sexual Transmission ◽  
Limited Disease ◽  
Zikv Infection ◽  
Blood Sucking

Zika virus (ZIKV) is a single-stranded RNA virus belonging to the arthropod-borne flaviviruses (arboviruses) which are mainly transmitted by blood-sucking mosquitoes of the genus Aedes. ZIKV infection has been known to be rather asymptomatic or presented as febrile self-limited disease; however, during the last decade the manifestation of ZIKV infection has been associated with a variety of neuroimmunological disorders including Guillain–Barré syndrome, microcephaly and other central nervous system abnormalities. More recently, there is accumulating evidence about sexual transmission of ZIKV, a trait that has never been observed in any other mosquito-borne flavivirus before. This article reviews the latest information regarding the latter and emerging role of ZIKV, focusing on the consequences of ZIKV infection on the male reproductive system and the epidemiology of human-to-human sexual transmission.

scholarly journals Late Neurological Consequences of Zika Virus Infection: Risk Factors and Pharmaceutical Approaches

2019 ◽  
Vol 12 (2) ◽  
pp. 60 ◽  
Author(s):  
Isis N. O. Souza ◽  
Fernanda G. Q. Barros-Aragão ◽  
Paula S. Frost ◽  
Claudia P. Figueiredo ◽  
Julia R. Clarke
Keyword(s):  
Zika Virus ◽  
Late Onset ◽  
Neurological Complications ◽  
Therapeutic Approaches ◽  
Zikv Infection ◽  
Clinical Surveillance ◽  
Infection Risk Factors

Zika virus (ZIKV) infection was historically considered a disease with mild symptoms and no major consequences to human health. However, several long-term, late onset, and chronic neurological complications, both in congenitally-exposed babies and in adult patients, have been reported after ZIKV infection, especially after the 2015 epidemics in the American continent. The development or severity of these conditions cannot be fully predicted, but it is possible that genetic, epigenetic, and environmental factors may contribute to determine ZIKV infection outcomes. This reinforces the importance that individuals exposed to ZIKV are submitted to long-term clinical surveillance and highlights the urgent need for the development of therapeutic approaches to reduce or eliminate the neurological burden of infection. Here, we review the epidemiology of ZIKV-associated neurological complications and the role of factors that may influence disease outcome. Moreover, we discuss experimental and clinical evidence of drugs that have shown promising results in vitro or in vitro against viral replication and and/or ZIKV-induced neurotoxicity.

scholarly journals Role of Gas6, TAM receptors ligand, in the pathogenesis of Zika virus infection

2019 ◽  
Author(s):  
Leticia Cristina S. Monteiro ◽  
João Luiz da Silva Filho ◽  
Jose Luiz Proença Modena ◽  
Fabio T. M. Costa
Keyword(s):  
Public Health ◽  
Virus Infection ◽  
Zika Virus ◽  
Zikv Infection ◽  
Neurological Sequelae ◽  
Tam Receptors ◽  
The World ◽  
Public Health Challenge

Zika virus (ZIKV) represents a public health challenge to Brazil and the rest of the world, especially because ZIKV infection has been linked to neurological sequelae, such as congenital fetal syndrome. Here, we aim to verify the role of Gas6 in the pathogenesis of ZIKV infection, by evaluating the expression of Gas6 and TAM receptors in patients infected by the virus with different degrees of disease severity, and infection of different human cells in vitro.

scholarly journals Diagnostic performance of anti-Zika virus IgM, IgAM and IgG ELISAs during co-circulation of Zika, dengue, and chikungunya viruses in Brazil and Venezuela

2021 ◽  
Vol 15 (4) ◽  
pp. e0009336
Author(s):  
Ivonne Morales ◽  
Kerstin D. Rosenberger ◽  
Tereza Magalhaes ◽  
Clarice N. L. Morais ◽  
Cynthia Braga ◽  
...  
Keyword(s):  
Zika Virus ◽  
Test Performance ◽  
Diagnostic Performance ◽  
Cross Reactivity ◽  
Rt Pcr ◽  
Zikv Infection ◽  
Serological Tests ◽  
Sequential Samples

Background Serological diagnosis of Zika virus (ZIKV) infection is challenging because of the antibody cross-reactivity among flaviviruses. At the same time, the role of Nucleic Acid Testing (NAT) is limited by the low proportion of symptomatic infections and the low average viral load. Here, we compared the diagnostic performance of commercially available IgM, IgAM, and IgG ELISAs in sequential samples during the ZIKV and chikungunya (CHIKV) epidemics and co-circulation of dengue virus (DENV) in Brazil and Venezuela. Methodology/Principal findings Acute (day of illness 1–5) and follow-up (day of illness ≥ 6) blood samples were collected from nine hundred and seven symptomatic patients enrolled in a prospective multicenter study of symptomatic patients recruited between June 2012 and August 2016. Acute samples were tested by RT-PCR for ZIKV, DENV, and CHIKV. Acute and follow-up samples were tested for IgM, IgAM, and IgG antibodies to ZIKV using commercially available ELISAs. Among follow-up samples with a RT-PCR confirmed ZIKV infection, anti-ZIKV IgAM sensitivity was 93.5% (43/48), while IgM and IgG exhibited sensitivities of 30.3% (10/35) and 72% (18/25), respectively. An additional 24% (26/109) of ZIKV infections were detected via IgAM seroconversion in ZIKV/DENV/CHIKV RT-PCR negative patients. The specificity of anti-ZIKV IgM was estimated at 93% and that of IgAM at 85%. Conclusions/Significance Our findings exemplify the challenges of the assessment of test performance for ZIKV serological tests in the real-world setting, during co-circulation of DENV, ZIKV, and CHIKV. However, we can also demonstrate that the IgAM immunoassay exhibits superior sensitivity to detect ZIKV RT-PCR confirmed infections compared to IgG and IgM immunoassays. The IgAM assay also proves to be promising for detection of anti-ZIKV seroconversions in sequential samples, both in ZIKV PCR-positive as well as PCR-negative patients, making this a candidate assay for serological monitoring of pregnant women in future ZIKV outbreaks.

scholarly journals Identification of Novel Natural Products as Effective and Broad-Spectrum Anti-Zika Virus Inhibitors

Viruses ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1019 ◽  
Author(s):  
Gao ◽  
Tai ◽  
Wang ◽  
Li ◽  
Jiang ◽  
...  
Keyword(s):  
Natural Products ◽  
Broad Spectrum ◽  
Zika Virus ◽  
The Other ◽  
Protein Domain ◽  
Mechanistic Study ◽  
Zikv Infection ◽  
Domain Iii ◽  
Almost All

Zika virus (ZIKV) infection during pregnancy leads to severe congenital Zika syndrome, which includes microcephaly and other neurological malformations. No therapeutic agents have, so far, been approved for the treatment of ZIKV infection in humans; as such, there is a need for a continuous effort to develop effective and safe antiviral drugs to treat ZIKV-caused diseases. After screening a natural product library, we have herein identified four natural products with anti-ZIKV activity in Vero E6 cells, including gossypol, curcumin, digitonin, and conessine. Except for curcumin, the other three natural products have not been reported before to have anti-ZIKV activity. Among them, gossypol exhibited the strongest inhibitory activity against almost all 10 ZIKV strains tested, including six recent epidemic human strains. The mechanistic study indicated that gossypol could neutralize ZIKV infection by targeting the envelope protein domain III (EDIII) of ZIKV. In contrast, the other natural products inhibited ZIKV infection by targeting the host cell or cell-associated entry and replication stages of ZIKV. A combination of gossypol with any of the three natural products identified in this study, as well as with bortezomib, a previously reported anti-ZIKV compound, exhibited significant combinatorial inhibitory effects against three ZIKV human strains tested. Importantly, gossypol also demonstrated marked potency against all four serotypes of dengue virus (DENV) human strains in vitro. Taken together, this study indicates the potential for further development of these natural products, particularly gossypol, as the lead compound or broad-spectrum inhibitors against ZIKV and other flaviviruses, such as DENV.

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