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https://www.readbyqxmd.com/read/28916719/kir2ds2-recognizes-conserved-peptides-derived-from-viral-helicases-in-the-context-of-hla-c
#1
Mohammed M Naiyer, Sorcha A Cassidy, Andrea Magri, Vanessa Cowton, Kevin Chen, Salah Mansour, Hariklia Kranidioti, Berenice Mbirbindi, Pauline Rettman, Scott Harris, Liam J Fanning, Arend Mulder, Franz H J Claas, Andrew D Davidson, Arvind H Patel, Marco A Purbhoo, Salim I Khakoo
Killer cell immunoglobulin-like receptors (KIRs) are rapidly evolving species-specific natural killer (NK) cell receptors associated with protection against multiple different human viral infections. We report that the activating receptor KIR2DS2 directly recognizes viral peptides derived from conserved regions of flaviviral superfamily 2 RNA helicases in the context of major histocompatibility complex class I. We started by documenting that peptide LNPSVAATL from the hepatitis C virus (HCV) helicase binds HLA-C*0102, leading to NK cell activation through engagement of KIR2DS2...
September 15, 2017: Science Immunology
https://www.readbyqxmd.com/read/28916391/zika-virus-structural-biology-and-progress-in-vaccine-development
#2
REVIEW
Hsiao-Han Lin, Bak-Sau Yip, Li-Min Huang, Suh-Chin Wu
The growing number of zika virus (ZIKV) infections plus a 20-fold increase in neonatal microcephaly in newborns in Brazil have raised alarms in many countries regarding the threat to pregnant women. Instances of microcephaly and central nervous system malformations continue to increase in ZIKV outbreak regions. ZIKV is a small enveloped positive-strand RNA virus belonging to the Flavivirus genus of the Flaviviridae family. High-resolution ZIKV structures recently identified by cryo-electron microscopy indicate that the overall ZIKV structure is similar to those of other flaviviruses...
September 12, 2017: Biotechnology Advances
https://www.readbyqxmd.com/read/28878076/zika-virus-infects-human-sertoli-cells-and-modulates-the-integrity-of-the-in-vitro-blood-testis-barrier-model
#3
David N Siemann, Daniel P Strange, Payal N Maharaj, Pei-Yong Shi, Saguna Verma
Confirmed reports of ZIKV in human seminal fluid for months after the clearance of viremia suggest the ability of ZIKV to establish persistent infection in the seminiferous tubules, an immune privileged site in the testis protected by the blood-testis barrier, also called the Sertoli cell barrier (SCB). However, cellular targets of ZIKV in human testis and mechanisms by which the virus enters seminiferous tubules remain unclear. We demonstrate that primary human SCs were highly susceptible to ZIKV as compared to the closely related dengue virus and induced expression of IFN-α, key cytokines and cell-adhesion molecules (VCAM-1 and ICAM-1)...
September 6, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28877637/ghost-probiotics-with-a-combined-regimen-a-novel-therapeutic-approach-against-the-zika-virus-an-emerging-world-threat
#4
Vivek K Bajpai, Vishal Chandra, Na-Hyung Kim, Rajni Rai, Pradeep Kumar, Kangmin Kim, Abhinav Aeron, Sun Chul Kang, D K Maheshwari, MinKyun Na, Irfan A Rather, Yong-Ha Park
The Zika virus (ZIKV) used to be an obscure flavivirus closely related to dengue virus (DENV). Transmission of this epidemic pathogen occurs mainly via mosquitoes, but it is also capable of placental and sexual transmission. Although the characteristics of these viruses are well defined, infections are unpredictable in terms of disease severity, unusual clinical manifestations, unexpected methods of transmission, long-term persistence, and the development of new strains. Recently, ZIKV has gained huge medical attention following the large-scale epidemics around the world, and reported cases of congenital abnormalities associated with Zika virus infections which have created a public health emergency of international concern...
September 7, 2017: Critical Reviews in Biotechnology
https://www.readbyqxmd.com/read/28869941/identifying-attenuating-mutations-tools-for-a-new-vaccine-design-against-flaviviruses
#5
Cécile Khou, Nathalie Pardigon
Emerging Flaviviruses pose an increasing threat to global human health. To date, human vaccines against yellow fever virus (YFV), Japanese encephalitis virus (JEV), dengue virus (DV), and tick-borne encephalitis virus (TBEV) exist. However, there is no human vaccine against other Flaviviruses such as Zika virus (ZIKV) and West Nile virus (WNV). In order to restrict their spread and to protect populations against the diseases they induce, vaccines against these emerging viruses must be designed. Obtaining new live attenuated Flavivirus vaccines using molecular biology methods is now possible...
September 5, 2017: Intervirology
https://www.readbyqxmd.com/read/28852878/compensating-for-cross-reactions-using-avidity-and-computation-in-a-suspension-multiplex-immunoassay-for-serotyping-of-zika-versus-other-flavivirus-infections
#6
Bengt Rönnberg, Åke Gustafsson, Olli Vapalahti, Petra Emmerich, Åke Lundkvist, Jonas Schmidt-Chanasit, Jonas Blomberg
The recent spread of Zika virus (ZIKV) in the Americas and Asia necessitates an increased preparedness for improved maternal and perinatal health and blood safety. However, serological cross-reactions, especially to Dengue virus (DENV), complicate ZIKV antibody serodiagnosis. A novel "pan-Flavi" suspension multiplex immunoassay (PFSMIA) using 25 antigens, whole virus (WV), non-structural protein 1 (NS1), and envelope (E) proteins, from 7 zoonotic flaviviruses for specific detection of ZIKV and DENV IgM and IgG was developed...
August 29, 2017: Medical Microbiology and Immunology
https://www.readbyqxmd.com/read/28846635/regulation-of-apoptosis-during-flavivirus-infection
#7
REVIEW
Toru Okamoto, Tatsuya Suzuki, Shinji Kusakabe, Makoto Tokunaga, Junki Hirano, Yuka Miyata, Yoshiharu Matsuura
Apoptosis is a type of programmed cell death that regulates cellular homeostasis by removing damaged or unnecessary cells. Its importance in host defenses is highlighted by the observation that many viruses evade, obstruct, or subvert apoptosis, thereby blunting the host immune response. Infection with Flaviviruses such as Japanese encephalitis virus (JEV), Dengue virus (DENV) and West Nile virus (WNV) has been shown to activate several signaling pathways such as endoplasmic reticulum (ER)-stress and AKT/PI3K pathway, resulting in activation or suppression of apoptosis in virus-infected cells...
August 28, 2017: Viruses
https://www.readbyqxmd.com/read/28835931/t-cell-responses-in-individuals-infected-with-zika-virus-and-in-those-vaccinated-against-dengue-virus
#8
Dominic Paquin-Proulx, Fabio E Leal, Cassia G Terrassani Silveira, Alvino Maestri, Claudia Brockmeyer, Shannon M Kitchen, Vinicius D Cabido, Esper G Kallas, Douglas F Nixon
BACKGROUND: The outbreak of Zika virus (ZIKV) infection in Brazil has raised concerns that infection during pregnancy could cause microcephaly and other severe neurodevelopmental malformations in the fetus. The mechanisms by which ZIKV causes fetal abnormalities are largely unknown. The importance of pre-infection with dengue virus (DENV), or other flaviviruses endemic to Brazil, remains to be investigated. It has been reported that antibodies directed against DENV can increase ZIKV infectivity by antibody dependent enhancement (ADE), suggesting that a history of prior DENV infection might worsen the outcome of ZIKV infection...
2017: Pathogens & Immunity
https://www.readbyqxmd.com/read/28815931/organization-of-the-flavivirus-rna-replicase-complex
#9
REVIEW
Carolin Brand, Martin Bisaillon, Brian J Geiss
Flaviviruses, such as dengue, Japanese encephalitis, West Nile, yellow fever, and Zika viruses, are serious human pathogens that cause significant morbidity and mortality globally each year. Flaviviruses are single-stranded, positive-sense RNA viruses, and encode two multidomain proteins, NS3 and NS5, that possess all enzymatic activities required for genome replication and capping. NS3 and NS5 interact within virus-induced replication compartments to form the RNA genome replicase complex. Although the individual enzymatic activities of both proteins have been extensively studied and are well characterized, there are still gaps in our understanding of how they interact to efficiently coordinate their respective activities during positive-strand RNA synthesis and capping...
August 16, 2017: Wiley Interdisciplinary Reviews. RNA
https://www.readbyqxmd.com/read/28798738/zika-virus-an-emerging-worldwide-threat
#10
Irfan A Rather, Jameel B Lone, Vivek K Bajpai, Woon K Paek, Jeongheui Lim
ZIKA virus (ZIKV) poses a severe threat to the world. Recent outbreaks of ZIKV after 2007 along with its quick transmission have made this virus a matter of international concern. The virus shows symptoms that are similar to those caused in the wake of dengue virus (DENV) and other flaviviruses, which makes it difficult to discern the viral infection. Diagnosis is further complicated as the virus cross-reacts with antibodies of other viruses. Currently, molecular diagnosis of the virus is being performed by RT-PCR and IgM-captured enzyme-linked immunosorbent assay (MAC-ELISA)...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28794181/a-neutralization-assay-for-zika-and-dengue-viruses-using-a-real-time-pcr-based-endpoint-assessment
#11
Heather L Wilson, Thomas Tran, Julian Druce, Myrielle Dupont-Rouzeyrol, Michael Catton
The global spread and infective complications of Zika virus (ZKV) and Dengue virus (DENV) have made them flaviviruses of public health concern. Serological diagnosis can be challenging due to antibody cross-reactivity, particularly in secondary flavivirus infections or when there is a history of flavivirus vaccination. The virus neutralization assay is considered to be the most specific assay for measurement of anti-flavivirus antibodies. This study describes an assay where neutralization endpoint is measured by real-time PCR, providing results within 72 hours...
August 9, 2017: Journal of Clinical Microbiology
https://www.readbyqxmd.com/read/28774800/highlights-of-the-30th-international-conference-on-antiviral-research
#12
Graciela Andrei, Kara Carter, Zlatko Janeba, Aruna Sampath, Luis M Schang, E Bart Tarbet, R Anthony Vere Hodge, Mike Bray, José A Esté
The 30th International Conference on Antiviral Research (ICAR) was held in Atlanta, GA, USA from May 18 to 21, 2017. This report provides an account of award lectures, invited keynote addresses and oral presentations during the meeting. The 2017 Gertrude Elion Memorial Lecture Award by Michael Sofia highlighted one of the most important accomplishments in recent drug discovery in antiviral research, the identification of the hepatitis C virus direct-acting antiviral sofosbuvir and new alternatives to combat hepatitis B virus (HBV) infection...
August 1, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28771605/impact-of-prior-flavivirus-immunity-on-zika-virus-infection-in-rhesus-macaques
#13
Michael K McCracken, Gregory D Gromowski, Heather L Friberg, Xiaoxu Lin, Peter Abbink, Rafael De La Barrera, Kenneth H Eckles, Lindsey S Garver, Michael Boyd, David Jetton, Dan H Barouch, Matthew C Wise, Bridget S Lewis, Jeffrey R Currier, Kayvon Modjarrad, Mark Milazzo, Michelle Liu, Anna B Mullins, J Robert Putnak, Nelson L Michael, Richard G Jarman, Stephen J Thomas
Studies have demonstrated cross-reactivity of anti-dengue virus (DENV) antibodies in human sera against Zika virus (ZIKV), promoting increased ZIKV infection in vitro. However, the correlation between in vitro and in vivo findings is not well characterized. Thus, we evaluated the impact of heterotypic flavivirus immunity on ZIKV titers in biofluids of rhesus macaques. Animals previously infected (≥420 days) with DENV2, DENV4, or yellow fever virus were compared to flavivirus-naïve animals following infection with a Brazilian ZIKV strain...
August 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28761113/cell-fusing-agent-virus-and-dengue-virus-mutually-interact-in-aedes-aegypti-cell-lines
#14
Guangmei Zhang, Sultan Asad, Alexander A Khromykh, Sassan Asgari
The genus Flavivirus contains more than 70 single-stranded, positive-sense arthropod-borne RNA viruses. Some flaviviruses are particularly medically important to humans and other vertebrates including dengue virus (DENV), West Nile virus, and yellow fever virus. These viruses are transmitted to vertebrates by mosquitoes and other arthropod species. Mosquitoes are also infected by insect-specific flaviviruses (ISFs) that do not appear to be infective to vertebrates. Cell fusing agent virus (CFAV) was the first described ISF, which was discovered in an Aedes aegypti cell culture...
July 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28758625/the-dengue-virus-non-structural-protein-1-ns1-is-secreted-from-infected-mosquito-cells-via-a-non-classical-caveolin-1-dependent-pathway
#15
Ana C Alcalá, Raiza Hernández-Bravo, Fernando Medina, David S Coll, Jose L Zambrano, Rosa M Del Angel, Juan E Ludert
Dengue virus NS1 is a glycoprotein of 46-50 kDa that is conserved among flaviviruses, associates as a dimer to cell membranes and is secreted as a hexamer to the extracellular milieu. Recent evidence showed that NS1 is secreted efficiently from infected mosquito cells. To explore the secretory route of NS1 in mosquito cells, infected cells were treated with brefeldin A (BFA) and methyl-beta-cyclodextrin (MβCD). The results showed that MβCD, but not BFA, significantly reduced the release of NS1. Moreover, silencing the expression of caveolin-1 (CAV1; a key component of the caveolar system that transports cholesterol inside the cell), but not SAR1 (a GTPase that participates in the classical secretory pathway), also results in a significant reduction of the secretion of NS1...
August 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28758019/current-trends-in-zika-vaccine-development
#16
EDITORIAL
Francisco A Lagunas-Rangel, Martha E Viveros-Sandoval, Arturo Reyes-Sandoval
The Zika virus (ZIKV) was first isolated in 1947 in Uganda. While it took 60 years for this virus to cause major outbreaks, an important shift in its ability to cause epidemics took place in the first and second decades of the this century: in 2007 in Yap Island, Micronesia, followed by French Polynesia in 2013 and, finally in 2015 and 2016, when ZIKV infections occurred throughout South America, Central America and the Caribbean, spreading rapidly to reach North America in just a single year. No licensed prophylactic vaccine is yet available but recent efforts towards the development of a vaccine have been remarkable from both the private and public sectors and include new candidate vaccines ranging from the classical live-attenuated or inactivated vaccines to more sophisticated approaches such as mRNA or genetically engineered viral platforms...
July 1, 2017: Journal of Virus Eradication
https://www.readbyqxmd.com/read/28757058/immune-correlates-of-protection-for-dengue-state-of-the-art-and-research-agenda
#17
Leah C Katzelnick, Eva Harris
Dengue viruses (DENV1-4) are mosquito-borne flaviviruses estimated to cause up to ∼400 million infections and ∼100 million dengue cases each year. Factors that contribute to protection from and risk of dengue and severe dengue disease have been studied extensively but are still not fully understood. Results from Phase 3 vaccine efficacy trials have recently become available for one vaccine candidate, now licensed for use in several countries, and more Phase 2 and 3 studies of additional vaccine candidates are ongoing, making these issues all the more urgent and timely...
August 24, 2017: Vaccine
https://www.readbyqxmd.com/read/28755304/participation-of-dengue-virus-ns4b-protein-in-the-modulation-of-immune-effectors-dependent-on-er-stress-in-insect-cells
#18
Karla J Sepúlveda-Salinas, José Ramos-Castañeda
Organisms' reactions to adverse events result in the generation of immune effectors, which, in the case of insects, may be produced from the direct activation of pathways such as Toll, Jak-STAT, Imd, or RNAi or may be derived from the crosstalk of different intracellular pathways. One such pathway, the unfolded protein response (UPR), has the primary objective of restoring homeostasis in the endoplasmic reticulum. In addition, the UPR participates in signaling crosstalk with the immune pathways, generating protection against pathogenic organisms...
July 28, 2017: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/28754189/progress-and-works-in-progress-update-on-flavivirus-vaccine-development
#19
REVIEW
Matthew H Collins, Stefan W Metz
Most areas of the globe are endemic for at least one flavivirus, putting billions at risk for infection. This diverse group of viral pathogens causes a range of manifestations in humans from asymptomatic infection to hemorrhagic fever to encephalitis to birth defects and even death. Many flaviviruses are transmitted by mosquitos and have expanded in geographic distribution in recent years, with dengue virus being the most prevalent, infecting approximately 400 million people each year. The explosive emergence of Zika virus in Latin America in 2014 refocused international attention on this medically important group of viruses...
July 25, 2017: Clinical Therapeutics
https://www.readbyqxmd.com/read/28750738/dengue-virus-evades-aav-mediated-neutralizing-antibody-prophylaxis-in-rhesus-monkeys
#20
Diogo M Magnani, Michael J Ricciardi, Varian K Bailey, Martin J Gutman, Núria Pedreño-Lopez, Cassia G T Silveira, Helen S Maxwell, Aline Domingues, Lucas Gonzalez-Nieto, Qin Su, Ruchi M Newman, Melissa Pack, Mauricio A Martins, José M Martinez-Navio, Sebastian P Fuchs, Eva G Rakasz, Todd M Allen, Stephen S Whitehead, Dennis R Burton, Guangping Gao, Ronald C Desrosiers, Esper G Kallas, David I Watkins
Development of vaccines against mosquito-borne Flaviviruses is complicated by the occurrence of antibody-dependent enhancement (ADE), which can increase disease severity. Long-term delivery of neutralizing antibodies (nAbs) has the potential to effectively block infection and represents an alternative to vaccination. The risk of ADE may be avoided by using prophylactic nAbs harboring amino acid mutations L234A and L235A (LALA) in the immunoglobulin G (IgG) constant region. Here, we used recombinant adeno-associated viruses (rAAVs) to deliver the anti-dengue virus 3 (DENV3) nAb P3D05...
July 24, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
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