scholarly journals Coordination of Zika Virus Infection and Viroplasm Organization by Microtubules and Microtubule-Organizing Centers

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3335
Author(s):  
Rebecca A. Buchwalter ◽  
Sarah C. Ogden ◽  
Sara B. York ◽  
Li Sun ◽  
Chunfeng Zheng ◽  
...  
Keyword(s):  
Zika Virus ◽  
Infectious Virus ◽  
Virus Production ◽  
Health Concern ◽  
Zikv Infection ◽  
Virus Particles ◽  
Microtubule Organizing Centers ◽  
Infected Cells ◽  
Congenital Microcephaly ◽  
A Site

Zika virus (ZIKV) became a global health concern in 2016 due to its links to congenital microcephaly and other birth defects. Flaviviruses, including ZIKV, reorganize the endoplasmic reticulum (ER) to form a viroplasm, a compartment where virus particles are assembled. Microtubules (MTs) and microtubule-organizing centers (MTOCs) coordinate structural and trafficking functions in the cell, and MTs also support replication of flaviviruses. Here we investigated the roles of MTs and the cell’s MTOCs on ZIKV viroplasm organization and virus production. We show that a toroidal-shaped viroplasm forms upon ZIKV infection, and MTs are organized at the viroplasm core and surrounding the viroplasm. We show that MTs are necessary for viroplasm organization and impact infectious virus production. In addition, the centrosome and the Golgi MTOC are closely associated with the viroplasm, and the centrosome coordinates the organization of the ZIKV viroplasm toroidal structure. Surprisingly, viroplasm formation and virus production are not significantly impaired when infected cells have no centrosomes and impaired Golgi MTOC, and we show that MTs are anchored to the viroplasm surface in these cells. We propose that the viroplasm is a site of MT organization, and the MTs organized at the viroplasm are sufficient for efficient virus production.

scholarly journals Zika virus is transmitted in neural progenitor cells via cell-to-cell spread and infection is inhibited by the autophagy inducer trehalose

2020 ◽  
pp. JVI.02024-20
Author(s):  
Alex E Clark ◽  
Zhe Zhu ◽  
Florian Krach ◽  
Jeremy N Rich ◽  
Gene W. Yeo ◽  
...  
Keyword(s):  
Viral Replication ◽  
Progenitor Cells ◽  
Zika Virus ◽  
Neural Progenitor Cells ◽  
Neutralizing Antibody ◽  
Neural Progenitor ◽  
Health Concern ◽  
Free Virus ◽  
Zikv Infection ◽  
Infected Cells

Zika virus (ZIKV) is a mosquito-borne human pathogen that causes congenital Zika syndrome and neurological symptoms in some adults. There are currently no approved treatments or vaccines for ZIKV, and exploration of therapies targeting host processes could avoid viral development of drug resistance. The purpose of our study was to determine if the non-toxic and widely used disaccharide trehalose, which showed antiviral activity against Human Cytomegalovirus (HCMV) in our previous work, could restrict ZIKV infection in clinically relevant neural progenitor cells (NPCs). Trehalose is known to induce autophagy, the degradation and recycling of cellular components. Whether autophagy is proviral or antiviral for ZIKV is controversial and depends on cell type and specific conditions used to activate or inhibit autophagy. We show here that trehalose treatment of NPCs infected with recent ZIKV isolates from Panama and Puerto Rico significantly reduces viral replication and spread. In addition, we demonstrate that ZIKV infection in NPCs spreads primarily cell-to-cell as an expanding infectious center, and NPCs are infected via contact with infected cells far more efficiently than by cell-free virus. Importantly, ZIKV was able to spread in NPCs in the presence of neutralizing antibody.Importance Zika virus causes birth defects and can lead to neurological disease in adults. While infection rates are currently low, ZIKV remains a public health concern with no treatment or vaccine available. Targeting a cellular pathway to inhibit viral replication is a potential treatment strategy that avoids development of antiviral resistance. We demonstrate in this study that the non-toxic autophagy-inducing disaccharide trehalose reduces spread and output of ZIKV in infected neural progenitor cells (NPCs), the major cells infected in the fetus. We show that ZIKV spreads cell-to-cell in NPCs as an infectious center and that NPCs are more permissive to infection by contact with infected cells than by cell-free virus. We find that neutralizing antibody does not prevent the spread of the infection in NPCs. These results are significant in demonstrating anti-ZIKV activity of trehalose and in clarifying the primary means of Zika virus spread in clinically relevant target cells.

scholarly journals SYNTHESIS OF VIRUS-SPECIFIC POLYMERS IN ADENOVIRUS-INFECTED CELLS: EFFECT OF 5-FLUORODEOXYURIDINE

1962 ◽  
Vol 116 (2) ◽  
pp. 141-157 ◽  
Author(s):  
John F. Flanagan ◽  
Harold S. Ginsberg
Keyword(s):  
Hela Cells ◽  
Culture Medium ◽  
Deoxyribonucleic Acid ◽  
Infectious Virus ◽  
Potent Inhibitor ◽  
Virus Production ◽  
Inhibitory Effect ◽  
Virus Particles ◽  
Specific Proteins ◽  
Infected Cells

Biochemical synthesis in adenovirus-infected HeLa cells was studied utilizing 5-fluorodeoxyuridine (5-FUDR), a potent inhibitor of deoxyribonucleic acid production. Synthesis of saline-soluble DNA and infectious virus was completely suppressed by addition of the analogue to cells as late as 10 hours after infection. The inhibitory effect of this compound was totally reversed by addition of 10–6 M thymidine to the culture medium. Synthesis of DNA essential for virus production began 10 hours after infection and was completed by 16 hours after infection. These data support the hypothesis that the saline-soluble DNA is a precursor of infectious virus particles. Studies of antigen production indicated that formation of virus-specific proteins was directly dependent upon synthesis of DNA.

scholarly journals Chloroquine inhibits Zika Virus infection in different cellular models

2016 ◽  
Author(s):  
Rodrigo Delvecchio ◽  
Luiza M Higa ◽  
Paula Pezzuto ◽  
Ana Luiza Valadão ◽  
Patrícia P Garcez ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Zika Virus ◽  
Antiviral Agents ◽  
Virus Production ◽  
Congenital Defects ◽  
Zikv Infection ◽  
Cytotoxic Effects ◽  
Cellular Models ◽  
Infected Cells

SummaryZika virus (ZIKV) infectionin uteromight lead to microcephaly and other congenital defects. In adults, cases of Guillain-Barré syndrome and meningoencephalitis associated with ZIKV infection have been reported, and no specific therapy is available so far. There is urgency for the discovery of antiviral agents capable of inhibiting viral replication and its deleterious effects. Chloroquine is widely administered as an antimalarial drug, anti-inflammatory agent, and it also shows antiviral activity against several viruses. Here we show that chloroquine exhibits antiviral activity against ZIKV in VERO, human brain microvascular endothelial, and neural stem cells. We demonstratedin vitrothat chloroquine reduces the number of ZIKV-infected cells, virus production and cell death promoted by ZIKV infection without cytotoxic effects. Our results suggest that chloroquine is a promising candidate for ZIKV clinical trials, since it is already approved for clinical use and can be safely administered to pregnant woman.

scholarly journals Palmitoleate Protects against Zika Virus-Induced Placental Trophoblast Apoptosis

Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 643
Author(s):  
Philma Glora Muthuraj ◽  
Aryamav Pattnaik ◽  
Prakash K. Sahoo ◽  
Md Torikul Islam ◽  
Asit K. Pattnaik ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Er Stress ◽  
Zika Virus ◽  
Intrauterine Growth Restriction ◽  
Maternal Circulation ◽  
Zikv Infection ◽  
Human Trophoblast ◽  
Homologous Protein ◽  
Stress Markers ◽  
Infected Cells

Zika virus (ZIKV) infection in pregnancy is associated with the development of microcephaly, intrauterine growth restriction, and ocular damage in the fetus. ZIKV infection of the placenta plays a crucial role in the vertical transmission from the maternal circulation to the fetus. Our previous study suggested that ZIKV induces endoplasmic reticulum (ER) stress and apoptosis of placental trophoblasts. Here, we showed that palmitoleate, an omega-7 monounsaturated fatty acid, prevents ZIKV-induced ER stress and apoptosis in placental trophoblasts. Human trophoblast cell lines (JEG-3 and JAR) and normal immortalized trophoblasts (HTR-8) were used. We observed that ZIKV infection of the trophoblasts resulted in apoptosis and treatment of palmitoleate to ZIKV-infected cells significantly prevented apoptosis. However, palmitate (saturated fatty acid) did not offer protection from ZIKV-induced ER stress and apoptosis. We also observed that the Zika viral RNA copies were decreased, and the cell viability improved in ZIKV-infected cells treated with palmitoleate as compared to the infected cells without palmitoleate treatment. Further, palmitoleate was shown to protect against ZIKV-induced upregulation of ER stress markers, C/EBP homologous protein and X-box binding protein-1 splicing in placental trophoblasts. In conclusion, our studies suggest that palmitoleate protects placental trophoblasts against ZIKV-induced ER stress and apoptosis.

scholarly journals A GFP Reporter MR766-Based Flow Cytometry Neutralization Test for Rapid Detection of Zika Virus-Neutralizing Antibodies in Serum Specimens

Vaccines ◽  
2019 ◽  
Vol 7 (3) ◽  
pp. 66 ◽  
Author(s):  
Frumence ◽  
Viranaicken ◽  
Gadea ◽  
Desprès
Keyword(s):  
Flow Cytometry ◽  
Zika Virus ◽  
Neutralizing Antibodies ◽  
Neutralization Test ◽  
Health Concern ◽  
Structural Protein ◽  
Adult Mice ◽  
Gfp Reporter ◽  
Infected Cells ◽  
High Level

Zika virus (ZIKV) is an emerging arthropod-borne virus of major public health concern. ZIKV infection is responsible for congenital Zika disease and other neurological defects. Antibody-mediated virus neutralization is an essential component of protective antiviral immunity against ZIKV. In the present study, we assessed whether our GFP reporter ZIKV derived from African viral strain MR766 could be useful for the development of a flow cytometry neutralization test (FNT), as an alternative to the conventional plaque-reduction neutralization test (PRNT). To improve the efficacy of GFP-expressing MR766, we selected virus variant MR766GFP showing a high level of GFP signal in infected cells. A MR766GFP-based FNT was assayed with immune sera from adult mice that received ZIKBeHMR-2. The chimeric ZIKV clone ZIKBeHMR-2 comprises the structural protein region of epidemic strain BeH819015 into MR766 backbone. We reported that adult mice inoculated with ZIKBeHMR-2 developed high levels of neutralizing anti-ZIKV antibodies. Comparative analysis between MR766GFP-based FNT and conventional PRNT was performed using mouse anti-ZIKBeHMR-2 immune sera. Indistinguishable neutralization patterns were observed when compared with PRNT50 and FNT50. We consider that the newly developed MR766GFP-based FNT is a valid format for measuring ZIKV-neutralizing antibodies in serum specimens.

scholarly journals A CYTOCHEMICAL DESCRIPTION OF THE MULTIPLICATION OF MENGOVIRUS IN L-929 CELLS

1962 ◽  
Vol 12 (1) ◽  
pp. 1-15 ◽  
Author(s):  
Richard M. Franklin
Keyword(s):  
Phase Contrast ◽  
Basic Protein ◽  
Virus Production ◽  
Cytological Change ◽  
Virus Particles ◽  
Contrast Microscopy ◽  
Infected Cells ◽  
Cytological Changes ◽  
Perinuclear Area

A correlation of cytochemical changes with virus production has been studied in L cells infected with Mengovirus. After a latent period of about 2 hours, virus was produced rapidly, reaching maximum titers of up to 12,000 particles per cell in 6 to 8 hours. The earliest cytological change was in the nucleus and consisted of a slight condensation of chromatin. There is no evidence, however, for the multiplication of either the viral RNA or protein in the nucleus. RNA, of high molecular weight, accumulated in the perinuclear area of the cytoplasm and was later found in inclusions. The perinuclear RNA was digestible with RNase and may be located in or on ribosomes. The inclusion RNA was resistant to RNase but could be removed by pepsin or potassium permanganate; it is probably in completed virus particles. Viral antigen was first observed in a perinuclear location and later in the above-mentioned inclusions. Although the viral protein contains appreciable amounts of arginine and lysine, it is not a basic protein of the histone type. Phase-contrast microscopy of living cells clearly demonstrated the role of the inclusions in release of virus from infected cells. A comparison is made between these cytological changes in Mengo-infected cells and those which have been found by other workers in polio-infected cells. There are many very similar changes.

scholarly journals STRUCTURE OF TYPE 5 ADENOVIRUS

1963 ◽  
Vol 118 (2) ◽  
pp. 295-306 ◽  
Author(s):  
Wesley C. Wilcox ◽  
Harold S. Ginsberg
Keyword(s):  
Virus Particle ◽  
Density Gradient ◽  
Infectious Virus ◽  
Relative Proportion ◽  
Specific Antigen ◽  
Equilibrium Density ◽  
Virus Particles ◽  
Infected Cells ◽  
Specific Antigens ◽  
Virus Antigens

Type 5 adenovirus was purified by fluorocarbon (freon 113) treatment followed by banding in a CsCl equilibrium density gradient. This method permitted separation of virus from normal host cell materials and virus-specific soluble antigens. Virus banded in CsCl with a mean bouyant density of 1.3349 gm/cm3. The three virus-specific soluble antigens (group- and type-specific antigens and toxin) banded together with a mean bouyant density of 1.2832 gm/cm3. The group-specific antigen was the predominant antigen of the purified virus particle, whereas the group- and type-specific antigens were present in equal titers in the antigen band. Infectious virus particles were inactivated by prolonged dialysis at pH 10.5. Centrifugation of inactivated virus preparations in a CsCl equilibrium density gradient resulted in separation of virus DNA from specific antigen: the antigens banded with a mean bouyant density of 1.2832 gm/cm3 and the DNA sedimented to the bottom of the tube. The predominant antigen derived from purified virus particles was the group-specific antigen and it was in the same relative proportion to the type-specific antigen as measured in intact particles. The antigens derived from disrupted virus were immunologically identical with the soluble virus antigens present in infected cells.

scholarly journals Super Resolution Microscopy and Deep Learning Identify Zika Virus Reorganization of the Endoplasmic Reticulum

2020 ◽  
Author(s):  
Rory K. M. Long ◽  
Kathleen P. Moriarty ◽  
Ben Cardoen ◽  
Guang Gao ◽  
A. Wayne Vogl ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Deep Learning ◽  
Viral Replication ◽  
Zika Virus ◽  
Deep Neural Networks ◽  
Super Resolution ◽  
Zikv Infection ◽  
Subcellular Organelle ◽  
Infected Cells ◽  
Super Resolution Microscopy

AbstractThe endoplasmic reticulum (ER) is a complex subcellular organelle composed of diverse structures such as tubules, sheets and tubular matrices. Flaviviruses such as Zika virus (ZIKV) induce reorganization of endoplasmic reticulum (ER) membranes to facilitate viral replication. Here, using 3D super resolution microscopy, ZIKV infection is shown to induce the formation of dense tubular matrices associated with viral replication in the central ER. Viral non-structural proteins NS4B and NS2B associate with replication complexes within the ZIKV-induced tubular matrix and exhibit distinct ER distributions outside this central ER region. Deep neural networks trained to identify ZIKV-infected versus mock-infected cells successfully identified ZIKV-induced central ER tubular matrices as a determinant of viral infection. Super resolution microscopy and deep learning are therefore able to identify and localize morphological features of the ER and may be of use to screen for inhibitors of infection by ER-reorganizing viruses.

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 Clinical Outcomes of a Zika Virus Mother–Child Pair Cohort in Spain

Pathogens ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 352 ◽  
Author(s):  
Antoni Soriano-Arandes ◽  
Marie Antoinette Frick ◽  
Milagros García López-Hortelano ◽  
Elena Sulleiro ◽  
Carlota Rodó ◽  
...  
Keyword(s):  
Zika Virus ◽  
Adverse Outcomes ◽  
Zikv Infection ◽  
Child Pair ◽  
Referral Hospitals ◽  
Congenital Zika Syndrome ◽  
Endemic Areas ◽  
Neurodevelopmental Abnormalities ◽  
Congenital Microcephaly

Background: Zika virus (ZIKV) infection has been associated with congenital microcephaly and other neurodevelopmental abnormalities. There is little published research on the effect of maternal ZIKV infection in a non-endemic European region. We aimed to describe the outcomes of pregnant travelers diagnosed as ZIKV-infected in Spain, and their exposed children. Methods: This prospective observational cohort study of nine referral hospitals enrolled pregnant women (PW) who travelled to endemic areas during their pregnancy or the two previous months, or those whose sexual partners visited endemic areas in the previous 6 months. Infants of ZIKV-infected mothers were followed for about two years. Results: ZIKV infection was diagnosed in 163 PW; 112 (70%) were asymptomatic and 24 (14.7%) were confirmed cases. Among 143 infants, 14 (9.8%) had adverse outcomes during follow-up; three had a congenital Zika syndrome (CZS), and 11 other potential Zika-related outcomes. The overall incidence of CZS was 2.1% (95%CI: 0.4–6.0%), but among infants born to ZIKV-confirmed mothers, this increased to 15.8% (95%CI: 3.4–39.6%). Conclusions: A nearly 10% overall risk of neurologic and hearing adverse outcomes was found in ZIKV-exposed children born to a ZIKV-infected traveler PW. Longer-term follow-up of these children is needed to assess whether there are any later-onset manifestations.

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