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Romy Conzade, Rebecca Grant, Mamunur Rahman Malik, Amgad Elkholy, Mohamed Elhakim, Dalia Samhouri, Peter K Ben Embarek, Maria D Van Kerkhove
Dromedary camels ( Camelus dromedarius ) are now known to be the vertebrate animal reservoir that intermittently transmits the Middle East respiratory syndrome coronavirus (MERS-CoV) to humans. Yet, details as to the specific mechanism(s) of zoonotic transmission from dromedaries to humans remain unclear. The aim of this study was to describe direct and indirect contact with dromedaries among all cases, and then separately for primary, non-primary, and unclassified cases of laboratory-confirmed MERS-CoV reported to the World Health Organization (WHO) between 1 January 2015 and 13 April 2018...
August 13, 2018: Viruses
Beatriz Perdiguero, Suresh C Raman, Cristina Sánchez-Corzo, Carlos Oscar S Sorzano, José Ramón Valverde, Mariano Esteban, Carmen Elena Gómez
An effective vaccine against Human Immunodeficiency Virus (HIV) still remains the best solution to provide a sustainable control and/or eradication of the virus. We have previously generated the HIV-1 vaccine modified vaccinia virus Ankara (MVA)-B, which exhibited good immunogenicity profile in phase I prophylactic and therapeutic clinical trials, but was unable to prevent viral rebound after antiretroviral (ART) removal. To potentiate the immunogenicity of MVA-B, here we described the design and immune responses elicited in mice by a new T cell multi-epitopic B (TMEP-B) immunogen, vectored by DNA, when administered in homologous or heterologous prime/boost regimens in combination with MVA-B...
August 13, 2018: Viruses
Eva Zusinaite, Aleksandr Ianevski, Diana Niukkanen, Minna M Poranen, Magnar Bjørås, Jan Egil Afset, Tanel Tenson, Vidya Velagapudi, Andres Merits, Denis E Kainov
There are dozens of approved, investigational and experimental antiviral agents. Many of these agents cause serious side effects, which can only be revealed after drug administration. Identification of the side effects prior to drug administration is challenging. Here we describe an ex vivo approach for studying immuno- and neuro-modulatory properties of antiviral agents, which may be associated with potential side effects of these therapeutics. The current approach combines drug toxicity/efficacy tests and transcriptomics, which is followed by mRNA, cytokine and metabolite profiling...
August 12, 2018: Viruses
Sang-Im Yun, Byung-Hak Song, Jordan C Frank, Justin G Julander, Aaron L Olsen, Irina A Polejaeva, Christopher J Davies, Kenneth L White, Young-Min Lee
Zika virus (ZIKV) causes no-to-mild symptoms or severe neurological disorders. To investigate the importance of viral and host genetic variations in determining ZIKV infection outcomes, we created three full-length infectious cDNA clones as bacterial artificial chromosomes for each of three spatiotemporally distinct and genetically divergent ZIKVs: MR-766 (Uganda, 1947), P6-740 (Malaysia, 1966), and PRVABC-59 (Puerto Rico, 2015). Using the three molecularly cloned ZIKVs, together with 13 ZIKV region-specific polyclonal antibodies covering nearly the entire viral protein-coding region, we made three conceptual advances: (i) We created a comprehensive genome-wide portrait of ZIKV gene products and their related species, with several previously undescribed gene products identified in the case of all three molecularly cloned ZIKVs...
August 11, 2018: Viruses
Tarryn Bourhill, Yoshinori Mori, Derrick E Rancourt, Maya Shmulevitz, Randal N Johnston
Oncolytic viruses show intriguing potential as cancer therapeutic agents. These viruses are capable of selectively targeting and killing cancerous cells while leaving healthy cells largely unaffected. The use of oncolytic viruses for cancer treatments in selected circumstances has recently been approved by the Food and Drug Administration (FDA) of the US and work is progressing on engineering viral vectors for enhanced selectivity, efficacy and safety. However, a better fundamental understanding of tumour and viral biology is essential for the continued advancement of the oncolytic field...
August 11, 2018: Viruses
David J Mock, Mark W Frampton, Joan E Nichols, Frank M Domurat, Denise J Signs, Norbert J Roberts
Monocytes-macrophages and lymphocytes are recruited to the respiratory tract in response to influenza virus challenge and are exposed to the virus during the establishment of immune defenses. The susceptibility of human lymphocytes to infection was assessed. The presence of monocytes-macrophages was required to attain infection of both resting and proliferating lymphocytes. Lymphocyte infection occurred in the context of immune cell clusters and was blocked by the addition of anti-intercellular adhesion molecule-1 (ICAM-1) antibody to prevent cell clustering...
August 10, 2018: Viruses
Hong-Su Park, Guanqun Liu, Qiang Liu, Yan Zhou
Nucleotide-binding domain and leucine-rich repeat-containing protein 3 (NLRP3) inflammasome plays a pivotal role in modulating lung inflammation in response to the influenza A virus infection. We previously showed that the swine influenza virus (SIV) infection induced NLRP3 inflammasome-mediated IL-1β production in primary porcine alveolar macrophages (PAMs), and we were interested in examining the upstream signaling events that are involved in this process. Here, we report that the SIV-infection led to dynamin-related protein 1 (DRP1) phosphorylation at serine 579 and mitochondrial fission in PAMs...
August 9, 2018: Viruses
Devinka Bamunusinghe, Matthew Skorski, Alicia Buckler-White, Christine A Kozak
Naturally-occurring lymphomagenesis is induced by mouse leukemia viruses (MLVs) carried as endogenous retroviruses (ERVs). Replicating the ecotropic MLVs recombines with polytropic (P-ERVs) and xenotropic ERVs (X-ERVs) to generate pathogenic viruses with an altered host range. While most recovered nonecotropic recombinants have a polytropic host range, the X-MLVs are also present in the pre-leukemic tissues. We analyzed two such isolates from the AKR mice to identify their ERV progenitors and to look for evidence of recombination...
August 9, 2018: Viruses
Yoko Matsuzaki, Kanetsu Sugawara, Yuki Furuse, Yoshitaka Shimotai, Seiji Hongo, Katsumi Mizuta, Hidekazu Nishimura
We mapped the hemagglutinin-esterase (HE) antigenic epitopes of the influenza C virus on the three-dimensional (3D) structure of the HE glycoprotein using 246 escape mutants that were selected by a panel of nine anti-HE monoclonal antibodies (MAbs), including seven of the C/Ann Arbor/1/50 virus and two of the C/Yamagata/15/2004 virus. The frequency of variant selection in the presence of anti-HE MAbs was very low, with frequencies ranging from 10-4.62 to 10-7.58 for the C/Ann Arbor/1/50 virus and from 10-7...
August 9, 2018: Viruses
Carla Mr Varanda, Patrick Materatski, Maria Doroteia Campos, Maria Ivone E Clara, Gustavo Nolasco, Maria do Rosário Félix
RNA silencing is an important defense mechanism in plants, yet several plant viruses encode proteins that suppress this mechanism. In this study, the genome of the Olive mild mosaic virus (OMMV) was screened for silencing suppressors. The full OMMV cDNA and 5 OMMV open reading frames (ORFs) were cloned into the Gateway binary vector pK7WG2, transformed into Agrobacterium tumefaciens , and agroinfiltrated into N. benthamiana 16C plants. CP and p6 showed suppressor activity, with CP showing significantly higher activity than p6 , yet activity that was lower than the full OMMV, suggesting a complementary action of CP and p6 ...
August 9, 2018: Viruses
Iztok Urbančič, Juliane Brun, Dilip Shrestha, Dominic Waithe, Christian Eggeling, Jakub Chojnacki
Human Immunodeficiency Virus type-1 (HIV-1) acquires its lipid membrane from the plasma membrane of the infected cell from which it buds out. Previous studies have shown that the HIV-1 envelope is an environment of very low mobility, with the diffusion of incorporated proteins two orders of magnitude slower than in the plasma membrane. One of the reasons for this difference is thought to be the HIV-1 membrane composition that is characterised by a high degree of rigidity and lipid packing, which has, until now, been difficult to assess experimentally...
August 8, 2018: Viruses
María Q Marín, Patricia Pérez, Carmen E Gómez, Carlos Óscar S Sorzano, Mariano Esteban, Juan García-Arriaza
Hepatitis C virus (HCV) represents a major global health problem for which a vaccine is not available. Modified vaccinia virus Ankara (MVA)-HCV is a unique HCV vaccine candidate based in the modified vaccinia virus Ankara (MVA) vector expressing the nearly full-length genome of HCV genotype 1a that elicits CD8⁺ T-cell responses in mice. With the aim to improve the immune response of MVA-HCV and because of the importance of interferon (IFN) in HCV infection, we deleted in MVA-HCV the vaccinia virus (VACV) C6L gene, encoding an inhibitor of IFN-β that prevents activation of the interferon regulatory factors 3 and 7 (IRF3 and IRF7)...
August 8, 2018: Viruses
Jingyou Yu, Shan-Lu Liu
Interferon inducible transmembrane proteins (IFITMs) are one of several IFN-stimulated genes (ISGs) that restrict entry of enveloped viruses, including flaviviruses, filoviruses and retroviruses. It has been recently reported that in U87 glioblastoma cells IFITM proteins inhibit HIV-1 entry in a co-receptor-dependent manner, that is, IFITM1 is more inhibitory on CCR5 tropic HIV-1 whereas IFITM2/3 confers a greater suppression of CXCR4 counterparts. However, how entry of HIV-1 with distinct co-receptor usage is modulated by different IFITM orthologs in physiologically relevant CD4⁺ T cells and monocytes/macrophages has not been investigated in detail...
August 7, 2018: Viruses
Gabriele Ibba, Claudia Piu, Elena Uleri, Caterina Serra, Antonina Dolei
The human endogenous retrovirus (HERV)-K, human mouse mammary tumor virus like-2 (HML-2) subgroup of HERVs is activated in several tumors and has been related to prostate cancer progression and motor neuron diseases. The cellular splicing factor 2/alternative splicing factor (SF2/ASF) is a positive regulator of gene expression, coded by a potent proto-oncogene, amplified, and abnormally expressed in tumors. TAR DNA-binding protein-43 (TDP-43) is a DNA/RNA-binding protein, negative regulator of alternative splicing, known for causing neurodegeneration, and with complex roles in oncogenesis...
August 7, 2018: Viruses
Anisha Mahendra Thanki, Grace Taylor-Joyce, Ahmed Dowah, Janet Yakubu Nale, Danish Malik, Martha Rebecca Jane Clokie
Bacteriophage (phage) therapy is a promising alternative to antibiotics for the treatment of bacterial pathogens, including Clostridium difficile . However, as for many species, in C. difficile the physical interactions between phages and bacterial cells have not been studied in detail. The initial interaction, known as phage adsorption, is initiated by the reversible attachment of phage tail fibers to bacterial cell surface receptors followed by an irreversible binding step. Therefore binding can dictate which strains are infected by the phage...
August 6, 2018: Viruses
Dean A McKeown, Joanna L Schroeder, Kim Stevens, Akira F Peters, Claudio A Sáez, Jihae Park, Mark D Rothman, John J Bolton, Murray T Brown, Declan C Schroeder
Two sister orders of the brown macroalgae (class Phaeophyceae), the morphologically complex Laminariales (commonly referred to as kelp) and the morphologically simple Ectocarpales are natural hosts for the dsDNA phaeoviruses (family Phycodnaviridae ) that persist as proviruses in the genomes of their hosts. We have previously shown that the major capsid protein (MCP) and DNA polymerase concatenated gene phylogeny splits phaeoviruses into two subgroups, A and B (both infecting Ectocarpales), while MCP-based phylogeny suggests that the kelp phaeoviruses form a distinct third subgroup C...
August 5, 2018: Viruses
Liyao Deng, Qiurui Zeng, Mingshu Wang, Anchun Cheng, Renyong Jia, Shun Chen, Dekang Zhu, Mafeng Liu, Qiao Yang, Ying Wu, Xinxin Zhao, Shaqiu Zhang, Yunya Liu, Yanling Yu, Ling Zhang, Xiaoyue Chen
Nuclear factor-κB (NF-κB) is an important transcription factor that induces the expression of antiviral genes and viral genes. NF-κB activation needs the activation of NF-κB upstream molecules, which include receptors, adaptor proteins, NF-κB (IκB) kinases (IKKs), IκBα, and NF-κB dimer p50/p65. To survive, viruses have evolved the capacity to utilize various strategies that inhibit NF-κB activity, including targeting receptors, adaptor proteins, IKKs, IκBα, and p50/p65. To inhibit NF-κB activation, viruses encode several specific NF-κB inhibitors, including NS3/4, 3C and 3C-like proteases, viral deubiquitinating enzymes (DUBs), phosphodegron-like (PDL) motifs, viral protein phosphatase (PPase)-binding proteins, and small hydrophobic (SH) proteins...
August 4, 2018: Viruses
Georges Herbein
Besides its well-described impact in immunosuppressed patients, the role of human cytomegalovirus (HCMV) in the pathogenesis of cancer has been more recently investigated. In cancer, HCMV could favor the progression and the spread of the tumor, a paradigm named oncomodulation. Although oncomodulation could account for part of the protumoral effect of HCMV, it might not explain the whole impact of HCMV infection on the tumor and the tumoral microenvironment. On the contrary cases have been reported where HCMV infection slows down the progression and the spread of the tumor...
August 3, 2018: Viruses
Daniel M Lyons, Adam S Lauring
Influenza remains a persistent public health challenge, because the rapid evolution of influenza viruses has led to marginal vaccine efficacy, antiviral resistance, and the annual emergence of novel strains. This evolvability is driven, in part, by the virus's capacity to generate diversity through mutation and reassortment. Because many new traits require multiple mutations and mutations are frequently combined by reassortment, epistatic interactions between mutations play an important role in influenza virus evolution...
August 3, 2018: Viruses
Thanuja Thekke-Veetil, Thien Ho, Joseph D Postman, Robert R Martin, Ioannis E Tzanetakis
A novel virus with distinct genome features was discovered by high throughput sequencing in a symptomatic blackcurrant plant. The virus, tentatively named Ribes americanum virus A (RAVA), has distinct genome organization and molecular features bridging genera in the order Tymovirales . The genome consists of 7106 nucleotides excluding the poly(A) tail. Five open reading frames were identified, with the first encoding a putative viral replicase with methyl transferase (MTR), AlkB, helicase, and RNA dependent RNA polymerase (RdRp) domains...
August 3, 2018: Viruses
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