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https://www.readbyqxmd.com/read/28598790/croi-2017-advances-in-antiretroviral-therapy
#1
Joyce Jones, Barbara S Taylor, Hong-Van Tieu, Timothy J Wilkin
The 2017 Conference on Retroviruses and Opportunistic Infections (CROI) featured exciting preclinical data on investigational antiretroviral agents with good in vitro efficacy and long half-lives. Investigational medications, including bictegravir, demonstrated excellent efficacy and tolerability, as did dual-agent therapy with dolutegravir paired with rilpivirine or with lamivudine. Dolutegravir monotherapy proved inadvisable due to virologic failure and resistance. The gap between high- and low-income settings along the HIV care continuum is narrowing, with Zimbabwe, Malawi, and Zambia approaching the 90-90-90 targets established by the joint United Nations Programme on HIV/AIDS (UNAIDS), whereas communities in the Southern United States are falling behind...
May 2017: Topics in Antiviral Medicine
https://www.readbyqxmd.com/read/28583207/knockdown-resistance-kdr-of-the-voltage-gated-sodium-channel-gene-of-aedes-aegypti-population-in-denpasar-bali-indonesia
#2
Penny Humaidah Hamid, Joko Prastowo, Anis Widyasari, Anja Taubert, Carlos Hermosilla
BACKGROUND: Aedes aegypti is the main vector of several arthropod-borne viral infections in the tropics profoundly affecting humans, such as dengue fever (DF), West Nile (WN), chikungunya and more recently Zika. Eradication of Aedes still largely depends on insecticides, which is the most cost-effective strategy, and often inefficient due to resistance development in exposed Aedes populations. We here conducted a study of Ae. aegypti resistance towards several insecticides regularly used in the city of Denpasar, Bali, Indonesia...
June 5, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/28572454/neurodevelopmental-protein-musashi-1-interacts-with-the-zika-genome-and-promotes-viral-replication
#3
Pavithra L Chavali, Lovorka Stojic, Luke W Meredith, Nimesh Joseph, Michael S Nahorski, Thomas J Sanford, Trevor R Sweeney, Ben A Krishna, Myra Hosmillo, Andrew E Firth, Richard Bayliss, Carlo L Marcelis, Susan Lindsay, Ian Goodfellow, C Geoffrey Woods, Fanni Gergely
A recent outbreak of Zika virus in Brazil has led to a simultaneous increase in reports of neonatal microcephaly. Zika targets cerebral neural precursors, a cell population essential for cortical development, but the cause of this neurotropism remains obscure. Here we report that the neural RNA-binding protein Musashi-1 (MSI1) interacts with the Zika genome and enables viral replication. Zika infection disrupts the binding of MSI1 to its endogenous targets, thereby deregulating expression of factors implicated in neural stem cell function...
June 1, 2017: Science
https://www.readbyqxmd.com/read/28539654/quasispecies-composition-and-evolution-of-a-typical-zika-virus-clinical-isolate-from-suriname
#4
Sander van Boheemen, Ali Tas, S Yahya Anvar, Rebecca van Grootveld, Irina C Albulescu, Martijn P Bauer, Mariet C Feltkamp, Peter J Bredenbeek, Martijn J van Hemert
The arthropod-borne Zika virus (ZIKV) is currently causing a major international public health threat in the Americas. This study describes the isolation of ZIKV from the plasma of a 29-year-old female traveler that developed typical symptoms, like rash, fever and headache upon return from Suriname. The complete genome sequence including the 5' and 3' untranslated regions was determined and phylogenetic analysis showed the isolate clustering within the Asian lineage, close to other viruses that have recently been isolated in the Americas...
May 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28538734/zika-virus-evolution-and-spread-in-the-americas
#5
Hayden C Metsky, Christian B Matranga, Shirlee Wohl, Stephen F Schaffner, Catherine A Freije, Sarah M Winnicki, Kendra West, James Qu, Mary Lynn Baniecki, Adrianne Gladden-Young, Aaron E Lin, Christopher H Tomkins-Tinch, Simon H Ye, Daniel J Park, Cynthia Y Luo, Kayla G Barnes, Rickey R Shah, Bridget Chak, Giselle Barbosa-Lima, Edson Delatorre, Yasmine R Vieira, Lauren M Paul, Amanda L Tan, Carolyn M Barcellona, Mario C Porcelli, Chalmers Vasquez, Andrew C Cannons, Marshall R Cone, Kelly N Hogan, Edgar W Kopp, Joshua J Anzinger, Kimberly F Garcia, Leda A Parham, Rosa M Gélvez Ramírez, Maria C Miranda Montoya, Diana P Rojas, Catherine M Brown, Scott Hennigan, Brandon Sabina, Sarah Scotland, Karthik Gangavarapu, Nathan D Grubaugh, Glenn Oliveira, Refugio Robles-Sikisaka, Andrew Rambaut, Lee Gehrke, Sandra Smole, M Elizabeth Halloran, Luis Villar, Salim Mattar, Ivette Lorenzana, Jose Cerbino-Neto, Clarissa Valim, Wim Degrave, Patricia T Bozza, Andreas Gnirke, Kristian G Andersen, Sharon Isern, Scott F Michael, Fernando A Bozza, Thiago M L Souza, Irene Bosch, Nathan L Yozwiak, Bronwyn L MacInnis, Pardis C Sabeti
Although the recent Zika virus (ZIKV) epidemic in the Americas and its link to birth defects have attracted a great deal of attention, much remains unknown about ZIKV disease epidemiology and ZIKV evolution, in part owing to a lack of genomic data. Here we address this gap in knowledge by using multiple sequencing approaches to generate 110 ZIKV genomes from clinical and mosquito samples from 10 countries and territories, greatly expanding the observed viral genetic diversity from this outbreak. We analysed the timing and patterns of introductions into distinct geographic regions; our phylogenetic evidence suggests rapid expansion of the outbreak in Brazil and multiple introductions of outbreak strains into Puerto Rico, Honduras, Colombia, other Caribbean islands, and the continental United States...
June 15, 2017: Nature
https://www.readbyqxmd.com/read/28529976/de-novo-generation-and-characterization-of-new-zika-virus-isolate-using-sequence-data-from-a-microcephaly-case
#6
Yin Xiang Setoh, Natalie A Prow, Nias Peng, Leon E Hugo, Gregor Devine, Jessamine E Hazlewood, Andreas Suhrbier, Alexander A Khromykh
Zika virus (ZIKV) has recently emerged and is the etiological agent of congenital Zika syndrome (CZS), a spectrum of congenital abnormalities arising from neural tissue infections in utero. Herein, we describe the de novo generation of a new ZIKV isolate, ZIKVNatal, using a modified circular polymerase extension reaction protocol and sequence data obtained from a ZIKV-infected fetus with microcephaly. ZIKVNatal thus has no laboratory passage history and is unequivocally associated with CZS. ZIKVNatal could be used to establish a fetal brain infection model in IFNAR(-/-) mice (including intrauterine growth restriction) without causing symptomatic infections in dams...
May 2017: MSphere
https://www.readbyqxmd.com/read/28515302/transposon-mutagenesis-of-the-zika-virus-genome-highlights-regions-essential-for-rna-replication-and-restricted-for-immune-evasion
#7
Benjamin O Fulton, David Sachs, Megan C Schwarz, Peter Palese, Matthew J Evans
The molecular constraints affecting Zika virus (ZIKV) evolution are not well understood. To investigate ZIKV genetic flexibility, we used transposon mutagenesis to add 15-nucleotide insertions throughout the MR766 ZIKV genome and subsequently deep sequenced the viable mutants. Few ZIKV insertion mutants replicated, which likely reflects a high degree of functional constraints on the genome. The NS1 gene exhibited distinct mutational tolerances at different stages of the screen. This result may define regions of the NS1 protein that are required for the different stages of the viral life cycle...
May 17, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28514450/evolutionary-enhancement-of-zika-virus-infectivity-in-aedes-aegypti-mosquitoes
#8
Yang Liu, Jianying Liu, Senyan Du, Chao Shan, Kaixiao Nie, Rudian Zhang, Xiao-Feng Li, Renli Zhang, Tao Wang, Cheng-Feng Qin, Penghua Wang, Pei-Yong Shi, Gong Cheng
Zika virus (ZIKV) remained obscure until the recent explosive outbreaks in French Polynesia (2013-2014) and South America (2015-2016). Phylogenetic studies have shown that ZIKV has evolved into African and Asian lineages. The Asian lineage of ZIKV was responsible for the recent epidemics in the Americas. However, the underlying mechanisms through which ZIKV rapidly and explosively spread from Asia to the Americas are unclear. Non-structural protein 1 (NS1) facilitates flavivirus acquisition by mosquitoes from an infected mammalian host and subsequently enhances viral prevalence in mosquitoes...
May 25, 2017: Nature
https://www.readbyqxmd.com/read/28509947/-arboviruses-also-have-an-american-dream
#9
F Rodhain
Some arboviruses that originated in the Old World have been introduced by humans into the American continent. The first of them was the yellow fever virus, coming from the West African coast with slaves in the 17th-19th centuries, followed by dengue viruses, which were always prevalent within the Americas. Next was theWest Nile virus, introduced in New York in 1999, that spread in only a few years over the whole continent. Then, Chikungunya virus arrived on Saint Martin Island in 2013 after its outbreak in Polynesia; it is now widespread in the Caribbean Islands and on the American continent from the United States to Brazil...
May 16, 2017: Bulletin de la Société de Pathologie Exotique
https://www.readbyqxmd.com/read/28435428/in-silico-cd4-cd8-t-cell-and-b-cell-immunity-associated-immunogenic-epitope-prediction-and-hla-distribution-analysis-of-zika-virus
#10
Essam Mohammed Janahi, Anupam Dhasmana, Vandana Srivastava, Aditya Narayan Sarangi, Sana Raza, Jamal M Arif, Madan Lal Bramha Bhatt, Mohtashim Lohani, Mohammed Yahya Areeshi, Anand Murari Saxena, Shafiul Haque
Zika virus (ZIKV) is a mosquito-borne flavivirus distributed all over Africa, South America and Asia. The infection with the virus may cause acute febrile sickness that clinically resembles dengue fever, yet there is no vaccine, no satisfactory treatment, and no means of evaluating the risk of the disease or prognosis in the infected people. In the present study, the efficacy of the host's immune response in reducing the risk of infectious diseases was taken into account to carry out immuno-informatics driven epitope screening strategy of vaccine candidates against ZIKV...
2017: EXCLI journal
https://www.readbyqxmd.com/read/28422757/cross-reactive-dengue-human-monoclonal-antibody-prevents-severe-pathologies-and-death-from-zika-virus-infections
#11
Yiu-Wing Kam, Cheryl Yi-Pin Lee, Teck-Hui Teo, Shanshan W Howland, Siti Naqiah Amrun, Fok-Moon Lum, Peter See, Nicholas Qing-Rong Kng, Roland G Huber, Mei-Hui Xu, Heng-Liang Tan, Andre Choo, Sebastian Maurer-Stroh, Florent Ginhoux, Katja Fink, Cheng-I Wang, Lisa F P Ng, Laurent Rénia
Zika virus (ZIKV) infections have been linked with neurological complications and congenital Zika syndrome. Given the high level of homology between ZIKV and the related flavivirus dengue virus (DENV), we investigated the level of cross-reactivity with ZIKV using a panel of DENV human mAbs. A majority of the mAbs showed binding to ZIKV virions, with several exhibiting neutralizing capacities against ZIKV in vitro. Three of the best ZIKV-neutralizing mAbs were found to recognize diverse epitopes on the envelope (E) glycoprotein: the highly conserved fusion-loop peptide, a conformation-specific epitope on the E monomer, and a quaternary epitope on the virion surface...
April 20, 2017: JCI Insight
https://www.readbyqxmd.com/read/28422157/detection-of-a-new-pyrethroid-resistance-mutation-v410l-in-the-sodium-channel-of-aedes-aegypti-a-potential-challenge-for-mosquito-control
#12
Khalid Haddi, Hudson V V Tomé, Yuzhe Du, Wilson R Valbon, Yoshiko Nomura, Gustavo F Martins, Ke Dong, Eugênio E Oliveira
The yellow fever mosquito, Aedes aegypti, particularly in Neotropical regions, is the principal vector of dengue, yellow fever, Zika and Chikungunya viruses. Pyrethroids remain one of the most used insecticides to control Aedes mosquitoes, despite the development of pyrethroid resistance in many mosquito populations worldwide. Here, we report a Brazilian strain of A. aegypti with high levels (approximately 100-60,000 fold) of resistance to both type I and type II pyrethroids. We detected two mutations (V410L and F1534C) in the sodium channel from this resistant strain...
April 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28408723/nucleic-acid-detection-with-crispr-cas13a-c2c2
#13
Jonathan S Gootenberg, Omar O Abudayyeh, Jeong Wook Lee, Patrick Essletzbichler, Aaron J Dy, Julia Joung, Vanessa Verdine, Nina Donghia, Nichole M Daringer, Catherine A Freije, Cameron Myhrvold, Roby P Bhattacharyya, Jonathan Livny, Aviv Regev, Eugene V Koonin, Deborah T Hung, Pardis C Sabeti, James J Collins, Feng Zhang
Rapid, inexpensive, and sensitive nucleic acid detection may aid point-of-care pathogen detection, genotyping, and disease monitoring. The RNA-guided, RNA-targeting clustered regularly interspaced short palindromic repeats (CRISPR) effector Cas13a (previously known as C2c2) exhibits a "collateral effect" of promiscuous ribonuclease activity upon target recognition. We combine the collateral effect of Cas13a with isothermal amplification to establish a CRISPR-based diagnostic (CRISPR-Dx), providing rapid DNA or RNA detection with attomolar sensitivity and single-base mismatch specificity...
April 28, 2017: Science
https://www.readbyqxmd.com/read/28396522/de-novo-assembly-of-viral-quasispecies-using-overlap-graphs
#14
Jasmijn A Baaijens, Amal Zine El Aabidine, Eric Rivals, Alexander Schönhuth
A viral quasispecies, the ensemble of viral strains populating an infected person, can be highly diverse. For optimal assessment of virulence, pathogenesis, and therapy selection, determining the haplotypes of the individual strains can play a key role. As many viruses are subject to high mutation and recombination rates, high-quality reference genomes are often not available at the time of a new disease outbreak. We present SAVAGE, a computational tool for reconstructing individual haplotypes of intra-host virus strains without the need for a high-quality reference genome...
May 2017: Genome Research
https://www.readbyqxmd.com/read/28351337/zika-virus-ns5-protein-potential-inhibitors-an-enhanced-in-silico-approach-in-drug-discovery
#15
Pritika Ramharack, Mahmoud E S Soliman
The re-emerging Zika virus (ZIKV) is an arthropod-borne virus that has been described to have explosive potential as a worldwide pandemic. The initial transmission of the virus was through a mosquito vector, however, evolving modes of transmission has allowed the spread of the disease over continents. The virus has already been linked to irreversible chronic central nervous system conditions. The concerns of the scientific and clinical community are the consequences of Zika viral mutations, thus suggesting the urgent need for viral inhibitors...
April 17, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/28347352/combined-target-site-kdr-mutations-play-a-primary-role-in-highly-pyrethroid-resistant-phenotypes-of-aedes-aegypti-from-saudi-arabia
#16
Ashwaq M Al Nazawi, Jabir Aqili, Mohammed Alzahrani, Philip J McCall, David Weetman
BACKGROUND: Pyrethroid resistance is a threat to effective vector control of Aedes aegypti, the vector of dengue, Zika and other arboviruses, but there are many major knowledge gaps on the mechanisms of resistance. In Jeddah and Makkah, the principal dengue-endemic areas of Saudi Arabia, pyrethroids are used widely for Ae. aegypti control but information about resistance remains sparse, and the underlying genetic basis is unknown. Findings from an ongoing study in this internationally significant area are reported here...
March 27, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/28347326/first-report-of-the-phe1534cys-kdr-mutation-in-natural-populations-of-aedes-albopictus-from-brazil
#17
Oscar Alexander Aguirre-Obando, Ademir Jesus Martins, Mário Antônio Navarro-Silva
BACKGROUND: Knockdown resistance (kdr), caused by alterations in the voltage-gated sodium channel (NaV), is one of the mechanisms responsible for pyrethroid (PY) resistance. In the Asian tiger mosquito, Aedes albopictus, at least four different mutations were described in the IIIS6 NaV segment in populations from Asia, North America and Europe. In contrast, in Aedes aegypti at least 12 non-synonymous mutations have been reported at nine different codons, mostly in the IIS6 and IIIS6 NaV segments...
March 27, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/28324177/a-detailed-analysis-of-codon-usage-patterns-and-influencing-factors-in-zika-virus
#18
Niraj K Singh, Anuj Tyagi
Recent outbreaks of Zika virus (ZIKV) in Africa, Latin America, Europe, and Southeast Asia have resulted in serious health concerns. To understand more about evolution and transmission of ZIKV, detailed codon usage analysis was performed for all available strains. A high effective number of codons (ENC) value indicated the presence of low codon usage bias in ZIKV. The effect of mutational pressure on codon usage bias was confirmed by significant correlations between nucleotide compositions at third codon positions and ENCs...
July 2017: Archives of Virology
https://www.readbyqxmd.com/read/28322690/biologic-evidence-required-for-zika-disease-enhancement-by-dengue-antibodies
#19
Scott B Halstead
The sudden appearance of overt human Zika virus infections that cross the placenta to damage fetal tissues, target sexual organs, and are followed in some instances by Guillain-Barré syndrome raises questions regarding whether these outcomes are caused by genetic mutations or if prior infection by other flaviviruses affects disease outcome. Because dengue and Zika viruses co-circulate in the urban Aedes aegypti mosquito-human cycle, a logical question, as suggested by in vitro data, is whether dengue virus infections result in antibody-dependent enhancement of Zika virus infections...
April 2017: Emerging Infectious Diseases
https://www.readbyqxmd.com/read/28289159/cutting-edge-innate-immune-augmenting-vesicular-stomatitis-virus-expressing-zika-virus-proteins-confers-protective-immunity
#20
Dillon Betancourt, Nina M G P de Queiroz, Tianli Xia, Jeonghyun Ahn, Glen N Barber
Zika virus (ZIKV) has become a serious public health concern because of its link to brain damage in developing human fetuses. Recombinant vesicular stomatitis virus (rVSV) was shown to be a highly effective and safe vector for the delivery of foreign immunogens for vaccine purposes. In this study, we generated rVSVs (wild-type and attenuated VSV with mutated matrix protein [VSVm] versions) that express either the full length ZIKV envelope protein (ZENV) alone or include the ZENV precursor to the membrane protein upstream of the envelope protein, and our rVSV-ZIKV constructs showed efficient immunogenicity in murine models...
March 13, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
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