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Yun-Na Zhang, Ya-Yun Liu, Fu-Chuan Xiao, Chun-Chun Liu, Xiao-Dong Liang, Jing Chen, Jing Zhou, Abdul Sattar Baloch, Lin Kan, Bin Zhou, Hua-Ji Qiu
The members of Flaviviridae utilize several endocytic pathways to enter a variety of host cells. Our previous work showed that classical swine fever virus (CSFV) enters porcine kidney (PK-15) cells through a clathrin-dependent pathway that requires Rab5 and Rab7. The entry mechanism for CSFV into other cell lines remains unclear, for instance, porcine alveolar macrophages (3D4/21 cells). More importantly, the trafficking of CSFV within endosomes controlled by Rab GTPases is unknown in 3D4/21 cells. In this study, entry and post-internalization of CSFV were analyzed using chemical inhibitors, RNA interference, and dominant negative (DN) mutants...
May 16, 2018: Journal of Virology
A L Baron, A Schoeniger, P Becher, C Baechlein
In recent years, hepatitis C virus (HCV)-related viruses were identified in several species including dogs, horses, bats and rodents. Additionally, a novel virus of the genus Hepacivirus has been discovered in bovine samples and was termed bovine hepacivirus (BovHepV). Prediction of the BovHepV IRES (internal ribosome entry site) structure revealed strong similarities to the HCV IRES structure comprising domains II, IIIabcde, pseudoknot IIIf and domain IV with the initiation codon AUG. Unlike HCV, only one microRNA-122 (miR-122) binding site could be identified in the BovHepV 5' NTR...
May 16, 2018: Journal of Virology
Adrián Díaz, Fernando S Flores, Agustín I Quaglia, Marta S Contigiani
St.Louis encephalitis virus (SLEV) is an emerging human pathogen flavivirus in Argentina. Recently, it has reemerged in the United States. We evaluated the role as amplifying host of six resident bird species and analyzed their capacity as host during the 2005 encephalitis outbreak of SLEV in Córdoba. Eared dove, picui ground dove, and house sparrow were the three species with highest host competence index. At a city level, eared doves and picui ground doves were the most important amplifying hosts during the 2005 SLEV human outbreak in Córdoba city...
May 14, 2018: American Journal of Tropical Medicine and Hygiene
Quentin Nevers, Isaac Ruiz, Nazim Ahnou, Flora Donati, Rozenn Brillet, Laurent Softic, Maxime Chazal, Nolwenn Jouvenet, Slim Fourati, Camille Baudesson, Patrice Bruscella, Muriel Gelin, Jean-François Guichou, Jean-Michel Pawlotsky, Abdelhakim Ahmed-Belkacem
Despite Flaviviridae viruses display high incidence, morbidity and mortality rates, the development of specific antiviral drugs for each virus is unlikely. Cyclophilins, a family of host peptidyl-prolyl cis / trans isomerase (PPIase), play a pivotal role in the lifecycle of many viruses and therefore represent an attractive target for broad-spectrum antiviral development. We report here the pan-genotypic anti-hepatitis C virus (HCV) activity of a small-molecule cyclophilin inhibitor (SMCypI). Mechanistic and modeling studies revealed that SMCypI bound to cyclophilin A in competition with Cyclosporin A (CsA), inhibited its PPIase activity and disrupted the CypA/NS5A interaction...
May 14, 2018: Antimicrobial Agents and Chemotherapy
Chelsea T Smartt, Dongyoung Shin, Seokyoung Kang, Walter J Tabachnick
We report a laboratory colony of Culex quinquefasciatus mosquitoes were experimentally able to salivate Zika virus (ZIKV, Flaviviridae; Flavivirus ) at 16 days post infection (dpi). ZIKV RNA was detected in bodies and in saliva deposited on filter paper cards with subsequent studies demonstrating the presence of live ZIKV in saliva.
2018: Frontiers in Microbiology
Shun Chen, Chao Yang, Wei Zhang, Suresh Mahalingam, Mingshu Wang, Anchun Cheng
Infections with viruses in the Flaviviridae family have a vast global and economic impact because of the high morbidity and mortality. The pathogenesis of Flaviviridae infections is very complex and not fully understood because these viruses can inhibit multiple immune pathways including the complement system, NK cells, and IFN induction and signalling pathways. The non-structural (NS) 5 and 5A proteins of Flaviviridae viruses are highly conserved and play an important role in resisting host immunity through various evasion mechanisms...
May 6, 2018: Pharmacology & Therapeutics
Weiwei Li, Baixing Wu, Wibowo Adian Soca, Lei An
Classical swine fever virus (CSFV) is the ringleader of Classical swine fever (CSF). The non-structural protein 5B (NS5B) encodes an RNA-dependent RNA polymerase (RdRp) that is a key enzyme initiating viral RNA replication by a de novo mechanism. It is also an attractive target for the development of anti-CSFV drugs. To gain a better understanding on the mechanism of CSFV RNA synthesis, here we solved the first crystal structure of CSFV-NS5B. Our studies show that the CSFV-NS5B RdRp contains characteristic fingers, palm domain and thumb domain as well as a unique N-terminal domain (NTD) that had never been observed...
May 2, 2018: Journal of Virology
Hassan T Tag-El-Din-Hassan, Masami Morimatsu, Takashi Agui
Up-to-date the flavivirus infection in avian taxa is not clearly defined. Several reports have demonstrated that many viruses belonging to Flaviviridae may cause diseases in poultry species; however, the susceptibility of other avian species is variable and still unclear. In human and mice, the 2'-5'-oligoadenylate synthetase (OAS) proteins are associated with resistance to the flavivirus infection as well as other virus infections. However, the avian OAS proteins are rarely studied. In our previous studies, we confirmed that the chicken OAS-like protein (chOASL) expressed OAS-enzymatic activity (the classical OAS/RNase L-dependent pathway) as well as the anti-flavivirus activity (the putative OAS/RNase L-independent pathway)...
April 28, 2018: Infection, Genetics and Evolution
N S Yudin, A V Barkhash, V N Maksimov, E V Ignatieva, A G Romaschenko
The identification of human predisposition genes to severe forms of infectious diseases is important for understanding the mechanisms of pathogenesis, as well as for the detection of the risk groups. This will allow one to carry out targeted vaccination and preventive therapy. The most common approaches to the genetic risk estimation include conducting association studies, in which the groups of patients and control individuals are compared using both preliminarily selected candidate genes and using genome-wide analysis...
March 2018: Molekuliarnaia Biologiia
Tatsuhiko Ozawa, Hideyuki Masaki, Tomohiko Takasaki, Ikuko Aoyama, Takahiro Yumisashi, Atsushi Yamanaka, Eiji Konishi, Yoh Ohnuki, Atsushi Muraguchi, Hiroyuki Kishi
West Nile virus (WNV) is a positive-sense single-stranded RNA flavivirus belonging to the Japanese encephalitis virus (JEV) serocomplex of the Flaviviridae family and causes mosquito-borne infections. Although most human infection cases are asymptomatic, approximately one in 150 infected individuals develops meningoencephalitis, with a mortality rate of 4-14%. While the development of human neutralizing antibody therapeutics against WNV is strongly anticipated, WNV is difficult to study in conventional laboratories due to its high safety level requirement...
April 14, 2018: Antiviral Research
Russell B Davidson, Josie Hendrix, Brian J Geiss, Martin McCullagh
The C-terminus domain of non-structural 3 (NS3) protein of the Flaviviridae viruses (e.g. HCV, dengue, West Nile, Zika) is a nucleotide triphosphatase (NTPase) -dependent superfamily 2 (SF2) helicase that unwinds double-stranded RNA while translocating along the nucleic polymer. Due to these functions, NS3 is an important target for antiviral development yet the biophysics of this enzyme are poorly understood. Microsecond-long molecular dynamic simulations of the dengue NS3 helicase domain are reported from which allosteric effects of RNA and NTPase substrates are observed...
April 2018: PLoS Computational Biology
Weiping Tang, Naling Zhu, Haiying Wang, Youwen Gao, Zhengwei Wan, Qundi Cai, Shouyi Yu, Shixing Tang
In 2013, two new viruses, equine pegivirus (EPgV) and Theiler's disease-associated virus (TDAV), both belonging to the genus Pegivirus within the family Flaviviridae, were identified. To investigate the geographical distribution and genetic diversity of these two viruses in China, we screened EPgV and TDAV infection in imported race horses and Chinese work horses by using reverse-transcription polymerase chain reaction (RT-PCR). EPgV was detected in 10.8 % (8/74) of the total horses tested, with a prevalence of 5...
April 16, 2018: Journal of General Virology
A K Chakraborty, A Karam, P Mukherjee, L Barkalita, P Borah, S Das, R Sanjukta, K Puro, S Ghatak, I Shakuntala, I Sharma, R G Laha, A Sen
The present study focused on the detection and genetic characterisation of 5' untranslated region (5'UTR) and E2 gene of classical swine fever virus (CSFV, family Flaviviridae , genus Pestivirus ) from bovine population of the northeastern region of India. A total of 134 cattle serum samples were collected from organised cattle farms and were screened for CSFV antigen with a commercial antigen capture enzyme linked immunosorbent assay (Ag-ELISA) and reverse transcription-polymerase chain reaction (RT-PCR). A total of 10 samples were positive for CSFV antigen by ELISA, while all of them were positive in PCR for 5'UTR region...
March 2018: Virusdisease
C Sadanandane, M D Gokhale, A Elango, P Yadav, D T Mourya, P Jambulingam
Kyasanur forest disease (KFD) is a major tick-borne viral haemorrhagic fever caused by KFD virus (KFDV) (Flaviviridae). The disease was reported to be confined to five districts of Karnataka state India until 2011. During 2012-2016, emergence of KFD has been reported in newer areas of Karnataka and adjoining states. Therefore, survey of tick vectors was carried out in these new areas of Karnataka and adjoining states reported with monkey deaths and human cases of KFD. In all selected sites, ticks from the forest floor were collected by lint clothes using flagging method...
March 28, 2018: Experimental & Applied Acarology
Michael Niepmann, Lyudmila A Shalamova, Gesche K Gerresheim, Oliver Rossbach
Hepatitis C virus (HCV) preferentially replicates in the human liver and frequently causes chronic infection, often leading to cirrhosis and liver cancer. HCV is an enveloped virus classified in the genus Hepacivirus in the family Flaviviridae and has a single-stranded RNA genome of positive orientation. The HCV RNA genome is translated and replicated in the cytoplasm. Translation is controlled by the Internal Ribosome Entry Site (IRES) in the 5' untranslated region (5' UTR), while also downstream elements like the cis -replication element (CRE) in the coding region and the 3' UTR are involved in translation regulation...
2018: Frontiers in Microbiology
Adam J Lopez-Denman, Alice Russo, Kylie M Wagstaff, Peter A White, David A Jans, Jason M Mackenzie
West Nile Virus (WNV) is a single stranded, positive sense RNA virus of the family Flaviviridae, and is a significant pathogen of global medical importance. Flavivirus replication is known to be exclusively cytoplasmic, but we show here for the first time that access to the nucleus of the WNV strain Kunjin (WNVKUN ) RNA-dependent RNA polymerase (protein NS5) is central to WNVKUN virus production. We show that treatment of cells with the specific nuclear export inhibitor leptomycin B (LMB) results in increased NS5 nuclear accumulation in WNVKUN -infected cells and NS5 transfected cells, indicative of nucleocytoplasmic shuttling under normal conditions...
March 26, 2018: Cellular Microbiology
Guoli Shi, Tetsuro Suzuki
Hepatitis C virus (HCV), a major etiologic agent of human liver diseases, is a positive-sense single-stranded RNA virus and is classified in the Flaviviridae family. Although research findings for the assembly of HCV particles are accumulating due to development of HCV cell culture system, the mechanism(s) by which the HCV genome becomes encapsidated remains largely unclear. In general, viral RNA represents only a small fraction of the RNA molecules in the cells infected with RNA viruses, but the viral genomic RNA is considered to selectively packaged into virions...
2018: Frontiers in Microbiology
Aaron C Brault, Bradley J Blitvich
The expanded use of next generation sequencing tools has led to an explosion in the rate of discovery of novel viral agents and has had a measured effect on the capacity to genetically identify the presence of previously described viruses in new geographic environments and within different hosts and vectors. For example, more than 30 flaviviruses ( Flavivirus ; Flaviviridae ) with the capacity to infect only mosquitoes have been described in the last 10 years. By contrast, only two such viruses had been described in the previous 33 years...
March 19, 2018: American Journal of Tropical Medicine and Hygiene
Michelle V Evans, Courtney C Murdock, John M Drake
New mosquito-borne diseases have emerged on multiple occasions over the last several decades, raising fears that there are yet more poorly understood viruses that may emerge in the USA. Here, we provide a data-driven 'watch list' of viruses in the Flaviviridae family with high potential to emerge in the USA, identified using statistical techniques, to enable the public health community to better target surveillance. We suggest that public health authorities further incorporate predictive modeling techniques into disease-prevention strategies...
March 15, 2018: Trends in Parasitology
Kombo F N'Guessan, Ceejay Boyce, Awewura Kwara, Timothy N A Archampong, Margaret Lartey, Kwamena W Sagoe, Ernest Kenu, Adjoa Obo-Akwa, Jason T Blackard
Human pegivirus (HPgV) is a positive single-stranded RNA virus in the Flaviviridae family. Phylogenetic analysis reveals the presence of multiple HPgV genotypes with distinct geographic locations. HPgV is of interest because of its potential beneficial impact on HIV disease progression. Despite this, the effects of HPgV in the context of other viral infections, such as hepatitis B virus (HBV), are poorly understood, and data from resource-limited settings are scarce. Therefore, we conducted a cross-sectional analysis of HPgV in HIV/HBV co-infected patients in Ghana...
March 17, 2018: Virus Genes
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