scholarly journals Higher Cytopathic Effects of a Zika Virus Brazilian Isolate from Bahia Compared to a Canadian-Imported Thai Strain

Viruses ◽  
2018 ◽  
Vol 10 (2) ◽  
pp. 53 ◽  
Author(s):  
Sergio Alpuche-Lazcano ◽  
Craig McCullogh ◽  
Olivier Del Corpo ◽  
Elodie Rance ◽  
Robert Scarborough ◽  
...  
Keyword(s):  
Zika Virus ◽  
Brazilian Isolate ◽  
Cytopathic Effects

scholarly journals Atlastin Endoplasmic Reticulum-Shaping Proteins Facilitate Zika Virus Replication

2019 ◽  
Vol 93 (23) ◽  
Author(s):  
Blandine Monel ◽  
Maaran Michael Rajah ◽  
Mohamed Lamine Hafirassou ◽  
Samy Sid Ahmed ◽  
Julien Burlaud-Gaillard ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Viral Replication ◽  
Zika Virus ◽  
Antiviral Treatment ◽  
Viral Proteins ◽  
Neurological Complications ◽  
Cytopathic Effects ◽  
Replication Sites ◽  
Infected Cells ◽  
Er Membrane

ABSTRACT The endoplasmic reticulum (ER) is the site for Zika virus (ZIKV) replication and is central to the cytopathic effects observed in infected cells. ZIKV induces the formation of ER-derived large cytoplasmic vacuoles followed by “implosive” cell death. Little is known about the nature of the ER factors that regulate flavivirus replication. Atlastins (ATL1, -2, and -3) are dynamin-related GTPases that control the structure and the dynamics of the ER membrane. We show here that ZIKV replication is significantly decreased in the absence of ATL proteins. The appearance of infected cells is delayed, the levels of intracellular viral proteins and released virus are reduced, and the cytopathic effects are strongly impaired. We further show that ATL3 is recruited to viral replication sites and interacts with the nonstructural viral proteins NS2A and NS2B3. Thus, proteins that shape and maintain the ER tubular network ensure efficient ZIKV replication. IMPORTANCE Zika virus (ZIKV) is an emerging virus associated with Guillain-Barré syndrome, and fetal microcephaly as well as other neurological complications. There is no vaccine or specific antiviral treatment against ZIKV. We found that endoplasmic reticulum (ER)-shaping atlastin proteins (ATL1, -2, and -3), which induce ER membrane fusion, facilitate ZIKV replication. We show that ATL3 is recruited to the viral replication site and colocalize with the viral proteins NS2A and NS2B3. The results provide insights into host factors used by ZIKV to enhance its replication.

scholarly journals Infection with a Brazilian isolate of Zika virus generates RIG‐I stimulatory RNA and the viral NS5 protein blocks type I IFN induction and signaling

2018 ◽  
Vol 48 (7) ◽  
pp. 1120-1136 ◽  
Author(s):  
Jonny Hertzog ◽  
Antonio Gregorio Dias Junior ◽  
Rachel E. Rigby ◽  
Claire L. Donald ◽  
Alice Mayer ◽  
...  
Keyword(s):  
Zika Virus ◽  
Type I ◽  
Type I Ifn ◽  
Brazilian Isolate ◽  
Protein Blocks

scholarly journals The Impact of African and Brazilian Zika virus isolates on neuroprogenitors

2016 ◽  
Author(s):  
Loraine Campanati ◽  
Luiza M. Higa ◽  
Rodrigo Delvecchio ◽  
Paula Pezzuto ◽  
Ana Luiza Valadão ◽  
...  
Keyword(s):  
Zika Virus ◽  
Neuroblastoma Cells ◽  
Brazilian Isolate ◽  
Human Neuroblastoma Cells ◽  
Human Neuroblastoma ◽  
Differentiation Potential ◽  
Neuronal Progenitors ◽  
The Impact ◽  
Virus Isolates

AbstractIn the last few months, an overwhelming number of people have been exposed to the Zika virus (ZIKV) in South and Central America. Here we showed, in vitro, that a Brazilian isolate impacts more severely murine neuronal progenitors and neurons than the African strain MR766. We found that the Brazilian isolate more pronouncedly inhibits neurite extension from neurospheres, alters their differentiation potential and causes neurons to have less and shorter processes. Comparing both lineages using a panel of inflammatory cytokines, we showed, with human neuroblastoma cells, that ZIKV induces the production of several inflammatory and chemotactic cytokines and once again, the Brazilian isolate had a more significant impact. Although much more needs to be studied regarding the association of ZIKV infection and brain damage during development, our study sheds some light into the differences between African and American lineages and the mechanisms by which the virus may be affecting neurogenesis.

scholarly journals Autopsy and Postmortem Studies Are Concordant: Pathology of Zika Virus Infection Is Neurotropic in Fetuses and Infants With Microcephaly Following Transplacental Transmission

2016 ◽  
Vol 141 (1) ◽  
pp. 68-72 ◽  
Author(s):  
David A. Schwartz
Keyword(s):  
Virus Infection ◽  
Brain Damage ◽  
Vertical Transmission ◽  
Zika Virus ◽  
In Vivo Studies ◽  
Cytopathic Effects ◽  
Zika Virus Infection ◽  
Postmortem Studies

Context.—Pathology studies have been important in concluding that Zika virus infection occurring in pregnant women can result in vertical transmission of the agent from mother to fetus. Fetal and infant autopsies have provided crucial direct evidence that Zika virus can infect an unborn child, resulting in microcephaly, other malformations, and, in some cases, death. Objective.—To better understand the etiologic role and mechanism(s) of Zika virus in causing birth defects such as microcephaly, this communication analyzes the spectrum of clinical and autopsy studies reported from fetuses and infants who developed intrauterine Zika virus infection, and compares these findings with experimental data related to Zika virus infection. Design.—Retrospective analysis of reported clinical, autopsy, pathology, and related postmortem studies from 9 fetuses and infants with intrauterine Zika virus infection and microcephaly. Results.—All fetuses and infants examined demonstrated an overlapping spectrum of gross and microscopic neuropathologic abnormalities. Direct cytopathic effects of infection by the Zika virus were confined to the brain; in cases where other organs were evaluated, no direct viral effects were identified. Conclusions.—There is concordance of the spectrum of brain damage, reinforcing previous data indicating that the Zika virus has a strong predilection for cells of the fetal central nervous system following vertical transmission. The occurrence of additional congenital abnormalities suggests that intrauterine brain damage from Zika virus interferes with normal fetal development, resulting in fetal akinesia. Experimental in vitro and in vivo studies of Zika virus infection corroborate the human autopsy findings of neural specificity.

scholarly journals Heparin prevents Zika virus induced-cytopathic effects in human neural progenitor cells

2017 ◽  
Vol 140 ◽  
pp. 13-17 ◽  
Author(s):  
Silvia Ghezzi ◽  
Lynsay Cooper ◽  
Alicia Rubio ◽  
Isabel Pagani ◽  
Maria Rosaria Capobianchi ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Zika Virus ◽  
Neural Progenitor Cells ◽  
Neural Progenitor ◽  
Cytopathic Effects ◽  
Human Neural Progenitor Cells

scholarly journals Zika virus replication and cytopathic effects in liver cells

PLoS ONE ◽  
2019 ◽  
Vol 14 (3) ◽  
pp. e0214016 ◽  
Author(s):  
Kenneth E. Sherman ◽  
Susan D. Rouster ◽  
Ling X. Kong ◽  
Matthew T. Aliota ◽  
Jason T. Blackard ◽  
...  
Keyword(s):  
Virus Replication ◽  
Zika Virus ◽  
Liver Cells ◽  
Cytopathic Effects

scholarly journals Doxycycline Interferes with Zika Virus Serine Protease and Inhibits Virus Replication in Human Skin Fibroblasts

Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4321
Author(s):  
Teow Chong Chong Teoh ◽  
Sawsam J. J. Al-Harbi ◽  
Ammar Yasir Abdulrahman ◽  
Hussin A. Rothan
Keyword(s):  
Human Skin ◽  
Virus Replication ◽  
Zika Virus ◽  
Inhibitory Effect ◽  
Human Skin Fibroblast ◽  
Cytopathic Effects ◽  
Skin Cells ◽  
Doxycycline Treatment ◽  
Human Skin Cells ◽  
Ns3 Protease

Zika virus (ZIKV) represents a re-emerging threat to global health due to its association with congenital birth defects. ZIKV NS2B-NS3 protease is crucial for virus replication by cleaving viral polyprotein at various junctions to release viral proteins and cause cytotoxic effects in ZIKV-infected cells. This study characterized the inhibitory effects of doxycycline against ZIKV NS2B-NS3 protease and viral replication in human skin cells. The in silico data showed that doxycycline binds to the active site of ZIKV protease at a low docking energy (−7.8 Kcal/mol) via four hydrogen bonds with the protease residues TYR1130, SER1135, GLY1151, and ASP83. Doxycycline efficiently inhibited viral NS2B-NS3 protease at average human temperature (37 °C) and human temperature with a high fever during virus infection (40 °C). Interestingly, doxycycline showed a higher inhibitory effect at 40 °C (IC50 = 5.3 µM) compared to 37 °C (9.9 µM). The virus replication was considerably reduced by increasing the concentration of doxycycline. An approximately 50% reduction in virus replication was observed at 20 µM of doxycycline. Treatment with 20 µM of doxycycline reduced the cytopathic effects (CPE), and the 40 µM of doxycycline almost eliminated the CPE of human skin cells. This study showed that doxycycline binds to the ZIKV protease and inhibits its catalytic activity at a low micro-molecular concentration range. Treatment of human skin fibroblast with doxycycline eliminated ZIKV infection and protected the cells against the cytopathic effects of the infection.

scholarly journals Targeting SUMO Modification of the Non-Structural Protein 5 of Zika Virus as a Host-Targeting Antiviral Strategy

2019 ◽  
Vol 20 (2) ◽  
pp. 392 ◽  
Author(s):  
Zheng Zhu ◽  
Hin Chu ◽  
Lei Wen ◽  
Shuofeng Yuan ◽  
Kenn Chik ◽  
...  
Keyword(s):  
Virus Replication ◽  
Zika Virus ◽  
Type I ◽  
Structural Protein ◽  
Post Translational Modification ◽  
Multiple Sequence ◽  
Sumo Modification ◽  
Cytopathic Effects ◽  
Modification Process

Post-translational modifications of host or viral proteins are key strategies exploited by viruses to support virus replication and counteract host immune response. SUMOylation is a post-translational modification process mediated by a family of ubiquitin-like proteins called small ubiquitin-like modifier (SUMO) proteins. Multiple sequence alignment of 78 representative flaviviruses showed that most (72/78, 92.3%) have a putative SUMO-interacting motif (SIM) at their non-structural 5 (NS5) protein’s N-terminal domain. The putative SIM was highly conserved among 414 pre-epidemic and epidemic Zika virus (ZIKV) strains, with all of them having a putative SIM core amino acid sequence of VIDL (327/414, 79.0%) or VVDL (87/414, 21.0%). Molecular docking predicted that the hydrophobic SIM core residues bind to the β2 strand of the SUMO-1 protein, and the acidic residues flanking the core strengthen the binding through interactions with the basic surface of the SUMO protein. The SUMO inhibitor 2-D08 significantly reduced replication of flaviviruses and protected cells against ZIKV-induced cytopathic effects in vitro. A SIM-mutated ZIKV NS5 failed to efficiently suppress type I interferon signaling. Overall, these findings may suggest SUMO modification of the viral NS5 protein to be an evolutionarily conserved post-translational modification process among flaviviruses to enhance virus replication and suppress host antiviral response.

Sign in / Sign up

Export Citation Format

Share Document