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Jyoti S Kumar, Divyasha Saxena, Manmohan Parida, Sivakumar Rathinam
Background & objectives: West Nile virus (WNV) is a mosquito-borne flavivirus. The disease can be diagnosed by isolation followed by fluorescent antibody tests, enzyme-linked immunosorbent assay and polymerase chain reaction (PCR) assay. These diagnostic methods are laborious and time-consuming. The present study was aimed to evaluate the real-time reverse-transcription loop-mediated isothermal amplification (RT-LAMP) method for rapid, early and accurate diagnosis of WNV. Methods: A one-step single tube accelerated quantitative RT-LAMP assay was evaluated by targeting the Env gene of WNV...
March 2018: Indian Journal of Medical Research
Joao Palma Pombo, Sumana Sanyal
Cellular lipid homeostasis is maintained through an intricately linked array of anabolic and catabolic pathways. Upon flavivirus infections, these are significantly altered: on the one hand, these viruses can co-opt lipid metabolic pathways to generate ATP to facilitate replication, or to synthesize membrane components to generate replication sites; on the other hand, more recent evidence suggests counter strategies employed by host cells, which actively modulate several of these networks in response to infection, enhancing interferon signaling by doing so, and thus creating an antiviral environment...
2018: Frontiers in Immunology
Qiang Ding, Jenna M Gaska, Florian Douam, Lei Wei, David Kim, Metodi Balev, Brigitte Heller, Alexander Ploss
The limited host tropism of numerous viruses causing disease in humans remains incompletely understood. One example is Zika virus (ZIKV), an RNA virus that has reemerged in recent years. Here, we demonstrate that ZIKV efficiently infects fibroblasts from humans, great apes, New and Old World monkeys, but not rodents. ZIKV infection in human-but not murine-cells impairs responses to agonists of the cGMP-AMP synthase/stimulator of IFN genes (cGAS/STING) signaling pathway, suggesting that viral mechanisms to evade antiviral defenses are less effective in rodent cells...
June 18, 2018: Proceedings of the National Academy of Sciences of the United States of America
Maria Rosaria Bassi, Raquel Navarro Sempere, Prashansa Meyn, Charlotta Polacek, Armando Arias
Flaviviruses constitute an increasing source of public health concern with growing numbers of pathogens causing disease, and a geographic spread to temperate climates. Despite a large body of evidence supporting mutagenesis as a conceivable antiviral strategy, there is currently no data on the sensitivity to increased mutagenesis for Zika virus (ZIKV) and Usutu virus (USUV), two emerging flaviviral threats. In this study, we demonstrate that both viruses are sensitive to three ribonucleosides that have shown mutagenic activity against other RNA viruses - favipiravir, ribavirin and 5-fluorouracil - while they remain unaffected by a mutagenic deoxyribonucleoside...
June 18, 2018: Antimicrobial Agents and Chemotherapy
Eliza M Kellman, Danielle K Offerdahl, Wessam Melik, Marshall E Bloom
Tick-borne flaviviruses have a global distribution and cause significant human disease, including encephalitis and hemorrhagic fever, and often result in neurologic sequelae. There are two distinct properties that determine the neuropathogenesis of a virus. The ability to invade the central nervous system (CNS) is referred to as the neuroinvasiveness of the agent, while the ability to infect and damage cells within the CNS is referred to as its neurovirulence. Examination of laboratory variants, cDNA clones, natural isolates with varying pathogenicity, and virally encoded immune evasion strategies have contributed extensively to our understanding of these properties...
June 16, 2018: Viruses
Xiaoyun Yang, Cheng Chen, Hongliang Tian, Heng Chi, Zhongyu Mu, Tianqing Zhang, Kailin Yang, Qi Zhao, Xiaohua Liu, Zefang Wang, Xiaoyun Ji, Haitao Yang
During its life cycle, Zika virus (ZIKV), an arthropod-borne flavivirus that is associated with Guillain-Barré syndrome and causes microencephaly in fetuses and newborn children, encodes a critical and indispensable helicase domain that has 5'-triphosphatase activity and performs ATP hydrolysis to generate energy and thus, sustains unwinding of double-stranded RNA during ZIKV genome replication. Of these processes, ATP hydrolysis represents the most basic event; however, its dynamic mechanisms remain largely unknown, impeding the further understanding of the function of ZIKV helicase and the ongoing anti-ZIKV drug design...
April 17, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Tricia Corrin, Judy Greig, Shannon Harding, Ian Young, Mariola Mascarenhas, Lisa A Waddell
BACKGROUND: Powassan virus (POWV), a flavivirus discovered in 1958, causes sporadic but severe cases of encephalitis in humans. Since 2007, the number of human Powassan cases diagnosed each year in the USA has steadily increased. This is in agreement with predictions that Powassan cases may increase in North America as a result of increased exposure to infected ticks. However, the increase may also reflect improved diagnostics and reporting among other factors. METHODS: A scoping review was prioritized to identify and characterize the global literature on POWV...
June 17, 2018: Zoonoses and Public Health
Rodrigo Gopar-Nieto, Nancy Libertad Chávez-Gómez, María Elisa González-Rentería, Luis Adrián Estrada-Loyo, Roberto de Jesús García-Avilés, Carlos Lenin Pliego-Reyes
The first report of chikungunya virus (CHIKV) in Mexico was in may 2014, in Jalisco, and has disseminated along the country in such a way that now is considered a relevant emergent vector-transmitted infection. It is clinically diagnosed by abrupt onset fever, asthenia, arthralgias, myalgias, headache and rash. In the clinical case, we described a women from Guerrero that had pulmonary symptomatology associated to CHIKV, which is an atypical clinical presentation that has been reported only in a hundred cases worldwide...
March 2018: Revista Médica del Instituto Mexicano del Seguro Social
Shannan L Rossi, Gregory D Ebel, Chao Shan, Pei-Yong Shi, Nikos Vasilakis
Zika virus (ZIKV) has challenged the assumed knowledge regarding the pathobiology of flaviviruses. Despite causing sporadic and mild disease in the 50 years since its discovery, Zika virus has now caused multiple outbreaks in dozens of countries worldwide. Moreover, the disease severity in recent outbreaks, with neurological disease in adult and devastating congenital malformations in fetuses, was not previously seen. One hypothesis is that the virus has acquired mutations that have increased its virulence...
June 11, 2018: Trends in Microbiology
Jingshu Zhang, Yun Lan, Ming Yuan Li, Mart Matthias Lamers, Maxime Fusade-Boyer, Elizabeth Klemm, Christoph Thiele, Joseph Ashour, Sumana Sanyal
Ubiquitylation is one of the most versatile protein post-translational modifications and is frequently altered during virus infections. Here we employed a functional proteomics screen to identify host proteins that are differentially ubiquitylated upon dengue virus (DENV) infection. Among the several differentially modified proteins identified in infected cells was AUP1, a lipid droplet-localized type-III membrane protein, which exists predominantly in the mono-ubiquitylated form. AUP1 associated with DENV NS4A and relocalized from lipid droplets to autophagosomes upon infection...
June 13, 2018: Cell Host & Microbe
L Cedillo-Barrón, J García-Cordero, G Shrivastava, S Carrillo-Halfon, M León-Juárez, J Bustos Arriaga, Pc León Valenzuela, B Gutiérrez Castañeda
Flaviviruses are positive, single-stranded, enveloped cytoplasmic sense RNA viruses that cause a variety of important diseases worldwide. Among them, Zika virus, West Nile virus, Japanese encephalitis virus, and Dengue virus have the potential to cause severe disease. Extensive studies have been performed to elucidate the structure and replication strategies of flaviviruses, and current studies are aiming to unravel the complex molecular interactions between the virus and host during the very early stages of infection...
2018: Sub-cellular Biochemistry
Lianpan Dai, Qihui Wang, Hao Song, George Fu Gao
Zika virus (ZIKV) is a re-emerged human pathogen, belonging to a super serogroup with dengue virus. Infection of ZIKV can lead to severe congenital symptoms, such as microcephaly, in newborns and Guillain-Barré syndrome in adults. To date, no prophylactics and therapeutics are available. Flavivirus envelope (E) protein represents the major target for neutralizing antibodies, while antibody response is the key correlate of protection against ZIKV infection. A panel of monoclonal antibodies (MAbs) were found to neutralize ZIKV infection and some of them exhibited strong potential as antivirals...
2018: Sub-cellular Biochemistry
Alan D T Barrett
Zika virus (ZIKV), a mosquito-borne flavivirus, was first identified in the 1940s in Uganda in Africa and emerged in the Americas in Brazil in May 2015. In the 30 months since ZIKV emerged as a major public health problem, spectacular progress has been made with vaccine development cumulating with the publication of three reports of phase 1 clinical trials in the 4th quarter of 2017. Clinical trials involving candidate DNA and purified inactivated virus vaccines showed all were safe and well-tolerated in the small number of volunteers and all induced neutralizing antibodies, although these varied by vaccine candidate and dosing regimen...
2018: NPJ Vaccines
Maximilian Koblischke, Karin Stiasny, Stephan W Aberle, Stefan Malafa, Georgios Tschouchnikas, Julia Schwaiger, Michael Kundi, Franz X Heinz, Judith H Aberle
Zika virus (ZIKV) has recently caused explosive outbreaks in Pacific islands, South- and Central America. Like with other flaviviruses, protective immunity is strongly dependent on potently neutralizing antibodies (Abs) directed against the viral envelope protein E. Such Ab formation is promoted by CD4 T cells through direct interaction with B cells that present epitopes derived from E or other structural proteins of the virus. Here, we examined the extent and epitope dominance of CD4 T cell responses to capsid (C) and envelope proteins in Zika patients...
2018: Frontiers in Immunology
Dawei Yan, Ying Shi, Haiwang Wang, Guoxin Li, Xuesong Li, Binbin Wang, Xin Su, Junheng Wang, Qiaoyang Teng, Jianmei Yang, Hongjun Chen, Qinfang Liu, Wenjun Ma, Zejun Li
Duck Tembusu virus (TMUV), like other mosquito-borne flaviviruses such as Japanese encephalitis virus (JEV), West Nile virus (WNV) and Bagaza virus (BAGV), is able to transmit vector-independently. To date, why these flaviviruses can be transmitted without mosquito vectors remains poorly understood. To explore the key molecular basis of flavivirus transmissibility, we compared virus replication and transmissibility of an early and a recent TMUV in ducks. The recent TMUV strain FX2010 replicated systemically and transmitted efficiently in ducks while the replication of early strain MM1775 was limited and did not transmit among ducks...
June 13, 2018: Journal of Virology
Scott Seitz, Penny Clarke, Kenneth L Tyler
Flaviviruses account for most arthropod-borne cases of human encephalitis in the world. However the exact mechanisms of injury to the central nervous system (CNS) during Flavivirus infections remain poorly understood. Microglia are the resident immune cell of the CNS and are important for multiple functions, including control of viral pathogenesis. Utilizing a pharmacologic method of microglia depletion (PLX5622, Plexxikon Inc, an inhibitor of colony stimulating factor 1 receptor) we sought to determine the role of microglia in Flaviviral pathogenesis...
June 13, 2018: Journal of Virology
Alberto Anastacio Amarilla, Marcilio Jorge Fumagalli, Mario Luis Figueiredo, Djalma S Lima-Junior, Nilton Nascimento Santos-Junior, Helda Liz Alfonso, Veronica Lippi, Amanda Cristina Trabuco, Flavio Lauretti, Vanessa Danielle Muller, David F Colón, João P M Luiz, Andreas Suhrbier, Yin Xiang Setoh, Alexander A Khromykh, Luiz Tadeu Moraes Figueiredo, Victor Hugo Aquino
Rocio virus (ROCV) was the causative agent of an unprecedented outbreak of encephalitis during the 1970s in the Vale do Ribeira, Sao Paulo State, in the Southeast region of Brazil. Surprisingly, no further cases of ROCV infection were identified after this outbreak; however, serological surveys have suggested the circulation of ROCV among humans and animals in different regions of Brazil. Cross-protective immunity among flaviviruses is well documented; consequently, immunity induced by infections with other flaviviruses endemic to Brazil could potentially be responsible for the lack of ROCV infections...
2018: PloS One
Sophie Masmejan, David Baud, Didier Musso, Alice Panchaud
Zika virus (ZIKV) recently emerged as a global public health emergency of international concern. ZIKV is responsible for severe neurological complications in adults and infection during pregnancy can lead to congenital Zika syndrome. There is no licensed vaccine or drug to prevent or treat ZIKV infection. Areas covered: The aim of this article is to provide an overview and update of the progress of research on anti-ZIKV vaccine and medications until the end of 2017, with a special emphasis on drugs that can be used during pregnancy...
June 13, 2018: Expert Review of Anti-infective Therapy
Samina Khan Yusufzai, Hasnah Osman, Mohammad Shaheen Khan, Basma M Abd Razik, Mohammed Oday Ezzat, Suriyati Mohamad, Othman Sulaiman, Jualang Azlan Gansau, Thaigarajan Parumasivam
A series of novel 4-thiazolidinone inhibitors SKYa-SKYg, containing coumarin as a core structure were synthesized via facile and efficient method. The structures of the synthesized compounds were established by extensive spectroscopic studies (FT IR, 1D NMR, 2D NMR, LC-MS) and elemental analysis. All the synthesized hybrids were further evaluated for their potential as anti-tubercular agents against Mycobacterium tuberculosis H37Rv ATCC 25618, and anti-bacterial agents against Escherichia coli, Enterobacter aerogenes, Salmonella typhi, Streptococcus pneumoniae and Staphylococcus aureus...
June 12, 2018: Chemistry Central Journal
Jessica S Russell, Leon Caly, Renata Kostecki, Sarah L McGuinness, Glen Carter, Dieter Bulach, Torsten Seemann, Tim P Stinear, Rob Baird, Mike Catton, Julian Druce
Murray Valley Encephalitis virus (MVEV) is a mosquito-borne Flavivirus. Clinical presentation is rare but severe, with a case fatality rate of 15⁻30%. Here we report a case of MVEV from the cerebrospinal fluid (CSF) of a patient in the Northern Territory in Australia. Initial diagnosis was performed using both MVEV-specific real-time, and Pan- Flavivirus conventional, Polymerase Chain Reaction (PCR), with confirmation by Sanger sequencing. Subsequent isolation, the first from CSF, was conducted in Vero cells and the observed cytopathic effect was confirmed by increasing viral titre in the real-time PCR...
June 11, 2018: Viruses
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