A Biomimetic Nanodecoy Traps Zika Virus To Prevent Viral Infection and Fetal Microcephaly Development

Nano Letters ◽  
2018 ◽  
Vol 19 (4) ◽  
pp. 2215-2222 ◽  
Author(s):  
Lang Rao ◽  
Wenbiao Wang ◽  
Qian-Fang Meng ◽  
Mingfu Tian ◽  
Bo Cai ◽  
...  
Keyword(s):  
Viruses ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 547
Author(s):  
Veronika Bernhauerová ◽  
Veronica V. Rezelj ◽  
Marco Vignuzzi

Mathematical models of in vitro viral kinetics help us understand and quantify the main determinants underlying the virus–host cell interactions. We aimed to provide a numerical characterization of the Zika virus (ZIKV) in vitro infection kinetics, an arthropod-borne emerging virus that has gained public recognition due to its association with microcephaly in newborns. The mathematical model of in vitro viral infection typically assumes that degradation of extracellular infectious virus proceeds in an exponential manner, that is, each viral particle has the same probability of losing infectivity at any given time. We incubated ZIKV stock in the cell culture media and sampled with high frequency for quantification over the course of 96 h. The data showed a delay in the virus degradation in the first 24 h followed by a decline, which could not be captured by the model with exponentially distributed decay time of infectious virus. Thus, we proposed a model, in which inactivation of infectious ZIKV is gamma distributed and fit the model to the temporal measurements of infectious virus remaining in the media. The model was able to reproduce the data well and yielded the decay time of infectious ZIKV to be 40 h. We studied the in vitro ZIKV infection kinetics by conducting cell infection at two distinct multiplicity of infection and measuring viral loads over time. We fit the mathematical model of in vitro viral infection with gamma distributed degradation time of infectious virus to the viral growth data and identified the timespans and rates involved within the ZIKV-host cell interplay. Our mathematical analysis combined with the data provides a well-described example of non-exponential viral decay dynamics and presents numerical characterization of in vitro infection with ZIKV.


2019 ◽  
Vol 34 (1) ◽  
pp. 106-110 ◽  
Author(s):  
Xiaodan Shi ◽  
Jingping Hu ◽  
Jing Guo ◽  
Chuanjian Wu ◽  
Sidong Xiong ◽  
...  

Author(s):  
Yu.V. Chumak ◽  
H. A. Loban ◽  
M. M. Ananieva ◽  
M. O. Faustova

The recent development of technologies of the laboratory systems in microbiology, providing detailed genome sequencing, has paved the ways for isolating new pathogens and carrying out in-depth study of long-known microorganisms. Moreover, the progressing of science and technology contributes to study changes in the ecology of microorganisms and the epidemiological characteristics of their spreading over the world. These advances enable scientists to find out some "new" diseases, known as emergent infectious diseases. Emergent diseases have emerged as a new type of rapidly evolving, long-known infectious diseases. A prime example of an emergent infection is the Zika virus (ZIKV). ZIKV belongs to the family Flaviviridae of the Flavivirus genus. It was first isolated from the blood of a rhesus macaque in 1947 in East Africa (Uganda), in the Zika forest, where its name came from. A year later, in the same area, ZIKV was detected in mosquitoes of the Aedes africanus genus. For a long time following the initial isolation of ZIKV, isolated sporadic cases of the disease caused by this pathogen were recorded in Asia and Africa. In 2007, an ZIKV outbreak was reported on the island of YAP (Micronesia). This was the first outbreak outside Asia and Africa. Zika virus is primarily transmitted by the bite of an infected mosquito from the Aedes genus in tropical and subtropical regions. But according to literature data, this virus can be spread by 17 species of mosquitoes of this genus. AE. aegypti and Ae. Albopictus have been known a leading role of spreading the infection. Considering that these mosquitoes are not only carriers of ZIKV, but also some other flavivirusiv representatives, their wide geographical distribution has become an issue of great concern. AE. aegypti mosquitoes are thermophilic and live only in tropical and subtropical climate zones and this fact has played as significant rope in the ZIKV spread. Ae. albopictus mosquitoes promote the circulation of this pathogen and cause a rapid expansion of the virus in the world, since this species has become widely distributed in countries of subtropical and temperate climate zones. To date, besides the main vector-borne transmission of the virus, there are a number of reports about ZIKV transplacental transmission from an infected mother to the foetus. ZIKV caused viral infection during the pregnancy results in microcephaly, a congenital condition associated with incomplete brain development and abnormally small size of the skull. This viral infection can also lead to such complications as miscarriage, stillbirth, and premature birth. According to the literature, there is the connection between ZIKV and not congenital CNS abnormalities, but also with Guillain-Barre syndrome. There have been publications on not only ZIKV mosquito transmission and transplacental transmission, but a few reports on ZIKV sexual transmission when no barrier contraceptives are used. ZIKV can be isolated from ejaculate within 14-28 days from the onset of the first symptoms of the disease.


Virology ◽  
2019 ◽  
Vol 526 ◽  
pp. 233
Author(s):  
Sandra Bos ◽  
Wildriss Viranaicken ◽  
Jonathan Turpin ◽  
Chaker El-Kalamouni ◽  
Marjolaine Roche ◽  
...  

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Rory K. M. Long ◽  
Kathleen P. Moriarty ◽  
Ben Cardoen ◽  
Guang Gao ◽  
A. Wayne Vogl ◽  
...  

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 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 distinguish 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 allow for better understanding of how ER morphology changes due to viral infection.


2018 ◽  
Vol 92 (9) ◽  
Author(s):  
Liping Yang ◽  
Rong Wang ◽  
Shixing Yang ◽  
Zexu Ma ◽  
Shaoli Lin ◽  
...  

ABSTRACTMovement of macromolecules between the cytoplasm and the nucleus occurs through the nuclear pore complex (NPC). Karyopherins comprise a family of soluble transport factors facilitating the nucleocytoplasmic translocation of proteins through the NPC. In this study, we found that karyopherin α6 (KPNA6; also known as importin α7) was required for the optimal replication of porcine reproductive and respiratory syndrome virus (PRRSV) and Zika virus (ZIKV), which are positive-sense, single-stranded RNA viruses replicating in the cytoplasm. The KPNA6 protein level in virus-infected cells was much higher than that in mock-infected controls, whereas the KPNA6 transcript remains stable. Viral infection blocked the ubiquitin-proteasomal degradation of KPNA6, which led to an extension of the KPNA6 half-life and the elevation of the KPNA6 level in comparison to mock-infected cells. PRRSV nsp12 protein induced KPNA6 stabilization. KPNA6 silencing was detrimental to the replication of PRRSV, and KPNA6 knockout impaired ZIKV replication. Moreover, KPNA6 knockout blocked the nuclear translocation of PRRSV nsp1β but had a minimal effect on two other PRRSV proteins with nuclear localization. Exogenous restitution of KPNA6 expression in the KPNA6-knockout cells results in restoration of the nuclear translocation of PRRSV nsp1β and the replication of ZIKV. These results indicate that KPNA6 is an important cellular factor for the replication of PRRSV and ZIKV.IMPORTANCEPositive-sense, single-stranded RNA (+ssRNA) viruses replicate in the cytoplasm of infected cells. The roles of transport factors in the nucleocytoplasmic trafficking system for the replication of +ssRNA viruses are not known. In this study, we discovered that PRRSV and ZIKV viruses needed karyopherin α6 (KPNA6), one of the transport factors, to enhance the virus replication. Our data showed that viral infection induced an elevation of the KPNA6 protein level due to an extension of the KPNA6 half-life via viral interference of the ubiquitin-proteasomal degradation of KPNA6. Notably, KPNA6 silencing or knockout dramatically reduced the replication of PRRSV and ZIKV. PRRSV nsp1β depended on KPNA6 to translocate into the nucleus. In addition, exogenous restitution of KPNA6 expression in KPNA6-knockout cells led to the restoration of nsp1β nuclear translocation and ZIKV replication. These results reveal a new aspect in the virus-cell interaction and may facilitate the development of novel antiviral therapeutics.


2020 ◽  
Author(s):  
J. Denis ◽  
A. Garnier ◽  
D. Claverie ◽  
F. De Laval ◽  
S. Attoumani ◽  
...  

AbstractAntibody kinetic curves obtained during a viral infection are often fitted using aggregated data from patients, hiding the heterogeneity of patient responses. The Wood equation makes it possible to establish the link between an individual’s kinetic profile and the disease, which may be helpful in identifying and studying clusters.


Cells ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 1444 ◽  
Author(s):  
Sandra Bos ◽  
Wildriss Viranaicken ◽  
Etienne Frumence ◽  
Ge Li ◽  
Philippe Desprès ◽  
...  

Emerging infections of mosquito-borne Zika virus (ZIKV) pose an increasing threat to human health, as documented over the recent years in South Pacific islands and the Americas in recent years. To better understand molecular mechanisms underlying the increase in human cases with severe pathologies, we recently demonstrated the functional roles of structural proteins capsid (C), pre-membrane (prM), and envelop (E) of ZIKV epidemic strains with the initiation of viral infection in human cells. Specifically, we found that the C-prM region contributes to permissiveness of human host cells to ZIKV infection and ZIKV-induced cytopathic effects, whereas the E protein is associated with viral attachment and early infection. In the present study, we further characterize ZIKV E proteins by investigating the roles of residues isoleucine 152 (Ile152), threonine 156 (Thr156), and histidine 158 (His158) (i.e., the E-152/156/158 residues), which surround a unique N-glycosylation site (E-154), in permissiveness of human host cells to epidemic ZIKV infection. For comparison purpose, we generated mutant molecular clones of epidemic BeH819015 (BR15) and historical MR766-NIID (MR766) strains that carry each other’s E-152/156/158 residues, respectively. We observed that the BR15 mutant containing the E-152/156/158 residues from MR766 was less infectious in A549-Dual™ cells than parental virus. In contrast, the MR766 mutant containing E-152/156/158 residues from BR15 displayed increased infectivity. The observed differences in infectivity were, however, not correlated with changes in viral binding onto host-cells or cellular responses to viral infection. Instead, the E-152/156/158 residues from BR15 were associated with an increased efficiency of viral membrane fusion inside infected cells due to conformational changes of E protein that enhance exposure of the fusion loop. Our data highlight an important contribution of E-152/156/158 residues to the early steps of ZIKV infection in human cells.


Sign in / Sign up

Export Citation Format

Share Document