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Viruses, Volume 6, Issue 7 (July 2014) – 17 articles , Pages 2531-2937

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1229 KiB  
Review
Coat as a Dagger: The Use of Capsid Proteins to Perforate Membranes during Non-Enveloped DNA Viruses Trafficking
by Eva Bilkova, Jitka Forstova and Levon Abrahamyan
Viruses 2014, 6(7), 2899-2937; https://doi.org/10.3390/v6072899 - 23 Jul 2014
Cited by 13 | Viewed by 7393
Abstract
To get access to the replication site, small non-enveloped DNA viruses have to cross the cell membrane using a limited number of capsid proteins, which also protect the viral genome in the extracellular environment. Most of DNA viruses have to reach the nucleus [...] Read more.
To get access to the replication site, small non-enveloped DNA viruses have to cross the cell membrane using a limited number of capsid proteins, which also protect the viral genome in the extracellular environment. Most of DNA viruses have to reach the nucleus to replicate. The capsid proteins involved in transmembrane penetration are exposed or released during endosomal trafficking of the virus. Subsequently, the conserved domains of capsid proteins interact with cellular membranes and ensure their efficient permeabilization. This review summarizes our current knowledge concerning the role of capsid proteins of small non-enveloped DNA viruses in intracellular membrane perturbation in the early stages of infection. Full article
(This article belongs to the Section Animal Viruses)
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1560 KiB  
Article
Full-Length Genome Analyses of Two New Simian Immunodeficiency Virus (SIV) Strains from Mustached Monkeys (C. Cephus) in Gabon Illustrate a Complex Evolutionary History among the SIVmus/mon/gsn Lineage
by Florian Liégeois, Fabian Schmidt, Vanina Boué, Christelle Butel, Fatima Mouacha, Paul Ngari, Bertrand Mve Ondo, Eric Leroy, Jonathan L. Heeney, Eric Delaporte, Martine Peeters and François Rouet
Viruses 2014, 6(7), 2880-2898; https://doi.org/10.3390/v6072880 - 22 Jul 2014
Cited by 11 | Viewed by 7365
Abstract
The Simian Immunodeficiency Virus (SIV) mus/mon/gsn lineage is a descendant of one of the precursor viruses to the HIV-1/SIVcpz/gor viral lineage. SIVmus and SIVgsn were sequenced from mustached and greater spot nosed monkeys in Cameroon and SIVmon from mona monkeys in Cameroon and [...] Read more.
The Simian Immunodeficiency Virus (SIV) mus/mon/gsn lineage is a descendant of one of the precursor viruses to the HIV-1/SIVcpz/gor viral lineage. SIVmus and SIVgsn were sequenced from mustached and greater spot nosed monkeys in Cameroon and SIVmon from mona monkeys in Cameroon and Nigeria. In order to further document the genetic diversity of SIVmus, we analyzed two full-length genomes of new strains identified in Gabon. The whole genomes obtained showed the expected reading frames for gag, pol, vif, vpr, tat, rev, env, nef, and also for a vpu gene. Analyses showed that the Gabonese SIVmus strains were closely related and formed a monophyletic clade within the SIVmus/mon/gsn lineage. Nonetheless, within this lineage, the position of both new SIVmus differed according to the gene analyzed. In pol and nef gene, phylogenetic topologies suggested different evolutions for each of the two new SIVmus strains whereas in the other nucleic fragments studied, their positions fluctuated between SIVmon, SIVmus-1, and SIVgsn. In addition, in C1 domain of env, we identified an insertion of seven amino acids characteristic for the SIVmus/mon/gsn and HIV‑1/SIVcpz/SIVgor lineages. Our results show a high genetic diversity of SIVmus in mustached monkeys and suggest cross-species transmission events and recombination within SIVmus/mon/gsn lineage. Additionally, in Central Africa, hunters continue to be exposed to these simian viruses, and this represents a potential threat to humans. Full article
(This article belongs to the Section Animal Viruses)
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729 KiB  
Review
Resistance Analyses of Integrase Strand Transfer Inhibitors within Phase 3 Clinical Trials of Treatment-Naive Patients
by Kirsten L. White, Francois Raffi and Michael D. Miller
Viruses 2014, 6(7), 2858-2879; https://doi.org/10.3390/v6072858 - 22 Jul 2014
Cited by 21 | Viewed by 5906
Abstract
The integrase (IN) strand transfer inhibitors (INSTIs), raltegravir (RAL), elvitegravir (EVG) and dolutegravir (DTG), comprise the newest drug class approved for the treatment of HIV-1 infection, which joins the existing classes of reverse transcriptase, protease and binding/entry inhibitors. The efficacy of first-line regimens [...] Read more.
The integrase (IN) strand transfer inhibitors (INSTIs), raltegravir (RAL), elvitegravir (EVG) and dolutegravir (DTG), comprise the newest drug class approved for the treatment of HIV-1 infection, which joins the existing classes of reverse transcriptase, protease and binding/entry inhibitors. The efficacy of first-line regimens has attained remarkably high levels, reaching undetectable viral loads in 90% of patients by Week 48; however, there remain patients who require a change in regimen due to adverse events, virologic failure with emergent resistance or other issues of patient management. Large, randomized clinical trials conducted in antiretroviral treatment-naive individuals are required for drug approval in this population in the US, EU and other countries, with the primary endpoint for virologic success at Week 48. However, there are differences in the definition of virologic failure and the evaluation of drug resistance among the trials. This review focuses on the methodology and tabulation of resistance to INSTIs in phase 3 clinical trials of first-line regimens and discusses case studies of resistance. Full article
(This article belongs to the Special Issue HIV Drug Resistance)
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1306 KiB  
Review
Membranous Replication Factories Induced by Plus-Strand RNA Viruses
by Inés Romero-Brey and Ralf Bartenschlager
Viruses 2014, 6(7), 2826-2857; https://doi.org/10.3390/v6072826 - 22 Jul 2014
Cited by 206 | Viewed by 15933
Abstract
In this review, we summarize the current knowledge about the membranous replication factories of members of plus-strand (+) RNA viruses. We discuss primarily the architecture of these complex membrane rearrangements, because this topic emerged in the last few years as electron tomography has [...] Read more.
In this review, we summarize the current knowledge about the membranous replication factories of members of plus-strand (+) RNA viruses. We discuss primarily the architecture of these complex membrane rearrangements, because this topic emerged in the last few years as electron tomography has become more widely available. A general denominator is that two “morphotypes” of membrane alterations can be found that are exemplified by flaviviruses and hepaciviruses: membrane invaginations towards the lumen of the endoplasmatic reticulum (ER) and double membrane vesicles, representing extrusions also originating from the ER, respectively. We hypothesize that either morphotype might reflect common pathways and principles that are used by these viruses to form their membranous replication compartments. Full article
(This article belongs to the Special Issue Electron Microscopy in Virus Diagnostics and Research)
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930 KiB  
Review
Mechanism of West Nile Virus Neuroinvasion: A Critical Appraisal
by Willy W. Suen, Natalie A. Prow, Roy A. Hall and Helle Bielefeldt-Ohmann
Viruses 2014, 6(7), 2796-2825; https://doi.org/10.3390/v6072796 - 18 Jul 2014
Cited by 93 | Viewed by 13452
Abstract
West Nile virus (WNV) is an important emerging neurotropic virus, responsible for increasingly severe encephalitis outbreaks in humans and horses worldwide. However, the mechanism by which the virus gains entry to the brain (neuroinvasion) remains poorly understood. Hypotheses of hematogenous and transneural entry [...] Read more.
West Nile virus (WNV) is an important emerging neurotropic virus, responsible for increasingly severe encephalitis outbreaks in humans and horses worldwide. However, the mechanism by which the virus gains entry to the brain (neuroinvasion) remains poorly understood. Hypotheses of hematogenous and transneural entry have been proposed for WNV neuroinvasion, which revolve mainly around the concepts of blood-brain barrier (BBB) disruption and retrograde axonal transport, respectively. However, an over‑representation of in vitro studies without adequate in vivo validation continues to obscure our understanding of the mechanism(s). Furthermore, WNV infection in the current rodent models does not generate a similar viremia and character of CNS infection, as seen in the common target hosts, humans and horses. These differences ultimately question the applicability of rodent models for pathogenesis investigations. Finally, the role of several barriers against CNS insults, such as the blood-cerebrospinal fluid (CSF), the CSF-brain and the blood-spinal cord barriers, remain largely unexplored, highlighting the infancy of this field. In this review, a systematic and critical appraisal of the current evidence relevant to the possible mechanism(s) of WNV neuroinvasion is conducted. Full article
(This article belongs to the Section Animal Viruses)
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Article
Identification of Luteolin as Enterovirus 71 and Coxsackievirus A16 Inhibitors through Reporter Viruses and Cell Viability-Based Screening
by Lin Xu, Weiheng Su, Jun Jin, Jiawen Chen, Xiaojun Li, Xuyuan Zhang, Meiyan Sun, Shiyang Sun, Peihu Fan, Dong An, Huafei Zhang, Xiguang Zhang, Wei Kong, Tonghui Ma and Chunlai Jiang
Viruses 2014, 6(7), 2778-2795; https://doi.org/10.3390/v6072778 - 17 Jul 2014
Cited by 63 | Viewed by 9022
Abstract
Hand, foot and mouth disease (HFMD) is a common pediatric illness mainly caused by infection with enterovirus 71 (EV71) and coxsackievirus A16 (CA16). The frequent HFMD outbreaks have become a serious public health problem. Currently, no vaccine or antiviral drug for EV71/CA16 infections [...] Read more.
Hand, foot and mouth disease (HFMD) is a common pediatric illness mainly caused by infection with enterovirus 71 (EV71) and coxsackievirus A16 (CA16). The frequent HFMD outbreaks have become a serious public health problem. Currently, no vaccine or antiviral drug for EV71/CA16 infections has been approved. In this study, a two-step screening platform consisting of reporter virus-based assays and cell viability‑based assays was developed to identify potential inhibitors of EV71/CA16 infection. Two types of reporter viruses, a pseudovirus containing luciferase-encoding RNA replicons encapsidated by viral capsid proteins and a full-length reporter virus containing enhanced green fluorescent protein, were used for primary screening of 400 highly purified natural compounds. Thereafter, a cell viability-based secondary screen was performed for the identified hits to confirm their antiviral activities. Three compounds (luteolin, galangin, and quercetin) were identified, among which luteolin exhibited the most potent inhibition of viral infection. In the cell viability assay and plaque reduction assay, luteolin showed similar 50% effective concentration (EC50) values of about 10 μM. Luteolin targeted the post-attachment stage of EV71 and CA16 infection by inhibiting viral RNA replication. This study suggests that luteolin may serve as a lead compound to develop potent anti-EV71 and CA16 drugs. Full article
(This article belongs to the Section Viral Immunology, Vaccines, and Antivirals)
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Article
Prevalence and Genotyping of High Risk Human Papillomavirus in Cervical Cancer Samples from Punjab, Pakistan
by Abida Siddiqa, Maidah Zainab, Ishtiaq Qadri, Muhammad Faraz Bhatti and Joanna L. Parish
Viruses 2014, 6(7), 2762-2777; https://doi.org/10.3390/v6072762 - 17 Jul 2014
Cited by 30 | Viewed by 8617
Abstract
Cervical cancer is the third most common cause of cancer-related death in women worldwide. Infection with high-risk human papillomavirus (HPV) is established as the cause of cervical carcinoma, therefore, high risk HPV detection may have prognostic significance for the women who are at [...] Read more.
Cervical cancer is the third most common cause of cancer-related death in women worldwide. Infection with high-risk human papillomavirus (HPV) is established as the cause of cervical carcinoma, therefore, high risk HPV detection may have prognostic significance for the women who are at increased risk of disease progression. The paucity of data on the incidence of cervical cancer in Pakistan makes it difficult to determine disease burden. Even less information is available regarding the prevalent HPV strains in cervical specimens collected from this region. Cervical cancer is a neglected disease in Pakistan in terms of screening, prevention, and vaccination. Identification and accurate genotyping of the virus burden in cancer specimens is important to inform intervention policies for future management of HPV associated disease and to potentially stratify patients dependent on HPV status. In this study, detection and genotyping of HPV types 16 and 18 from 77 cervical specimens were carried out. Consensus primers GP5+/GP6+, which detect 44 genital HPV types, and type specific primers (TS16 and TS18) were used in conjunction with newly designed type specific primers. Using a combination of these methods of detection, a total of 94.81% (95% CI ±4.95) of cervical lesions were positive for HPV. Single infections of HPV16 were detected in 24.68% (95% CI ±9.63) of total samples and HPV18 was found in 25.97% (95% CI ±9.79) samples. Interestingly, a high proportion of samples (40.26%, 95% CI ±10.95) was positive for both HPV16 and 18, indicating a higher incidence of co-infection than previously reported for similar ethnic regions. The HPV genotype of 3.90% of HPV positive samples remained undetected, although these samples were positive with the GP5+/GP6+ primer set indicating infection with an HPV type other than 16 or 18. These data indicate that the overall incidence of high risk HPV infection in cervical cancer and intraepithelial neoplasia specimens in Punjab, Pakistan is in line with the worldwide prevalence, but that the incidence of HPV16 and 18 co-infections in our cohort is higher than that previously reported. Full article
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827 KiB  
Review
Modified Vaccinia Virus Ankara (MVA) as Production Platform for Vaccines against Influenza and Other Viral Respiratory Diseases
by Arwen F. Altenburg, Joost H. C. M. Kreijtz, Rory D. De Vries, Fei Song, Robert Fux, Guus F. Rimmelzwaan, Gerd Sutter and Asisa Volz
Viruses 2014, 6(7), 2735-2761; https://doi.org/10.3390/v6072735 - 17 Jul 2014
Cited by 93 | Viewed by 21464
Abstract
Respiratory viruses infections caused by influenza viruses, human parainfluenza virus (hPIV), respiratory syncytial virus (RSV) and coronaviruses are an eminent threat for public health. Currently, there are no licensed vaccines available for hPIV, RSV and coronaviruses, and the available seasonal influenza vaccines have [...] Read more.
Respiratory viruses infections caused by influenza viruses, human parainfluenza virus (hPIV), respiratory syncytial virus (RSV) and coronaviruses are an eminent threat for public health. Currently, there are no licensed vaccines available for hPIV, RSV and coronaviruses, and the available seasonal influenza vaccines have considerable limitations. With regard to pandemic preparedness, it is important that procedures are in place to respond rapidly and produce tailor made vaccines against these respiratory viruses on short notice. Moreover, especially for influenza there is great need for the development of a universal vaccine that induces broad protective immunity against influenza viruses of various subtypes. Modified Vaccinia Virus Ankara (MVA) is a replication-deficient viral vector that holds great promise as a vaccine platform. MVA can encode one or more foreign antigens and thus functions as a multivalent vaccine. The vector can be used at biosafety level 1, has intrinsic adjuvant capacities and induces humoral and cellular immune responses. However, there are some practical and regulatory issues that need to be addressed in order to develop MVA-based vaccines on short notice at the verge of a pandemic. In this review, we discuss promising novel influenza virus vaccine targets and the use of MVA for vaccine development against various respiratory viruses. Full article
(This article belongs to the Special Issue Virus-based Vaccines)
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1930 KiB  
Article
Increased Plasma Cell-Free DNA Level during HTNV Infection: Correlation with Disease Severity and Virus Load
by Jing Yi, Yun Zhang, Yusi Zhang, Ying Ma, Chunmei Zhang, Qi Li, Bei Liu, Zhijia Liu, Jiayun Liu, Xianqing Zhang, Ran Zhuang and Boquan Jin
Viruses 2014, 6(7), 2723-2734; https://doi.org/10.3390/v6072723 - 15 Jul 2014
Cited by 21 | Viewed by 6462
Abstract
Cell-free DNA (cf-DNA) in blood represents a promising DNA damage response triggered by virus infection or trauma, tumor, etc. Hantavirus primarily causes two diseases: haemorrhagic fever with renal syndrome (HFRS) and Hantavirus cardiopulmonary syndrome (HCPS), depending on different Hantavirus species. The aim of [...] Read more.
Cell-free DNA (cf-DNA) in blood represents a promising DNA damage response triggered by virus infection or trauma, tumor, etc. Hantavirus primarily causes two diseases: haemorrhagic fever with renal syndrome (HFRS) and Hantavirus cardiopulmonary syndrome (HCPS), depending on different Hantavirus species. The aim of this study was to evaluate plasma cf-DNA levels in acute phase of HFRS, and to correlate plasma cf-DNA with disease severity and plasma Hanttan virus (HTNV) load. We observed the appearance of cf-DNA in 166 plasma samples from 76 HFRS patients: the plasma cf-DNA levels peaked at the hypotensive stage of HFRS, and then decreased gradually. Until the diuretic stage, there was no significant difference in plasma cf-DNA level between patients and the healthy control. Exclusively in the febrile/hypotensive stage, the plasma cf-DNA levels of severe/critical patients were higher than those of the mild/moderate group. Moreover, the plasma cf-DNA value in the early stage of HFRS was correlated with HTNV load and disease severity. In most of the patients, plasma cf-DNA displayed a low-molecular weight appearance, corresponding to the size of apoptotic DNA. In conclusion, the plasma cf-DNA levels were dynamically elevated during HFRS, and correlated with disease severity, which suggests that plasma cf-DNA may be a potential biomarker for the pathogenesis and prognosis of HFRS. Full article
(This article belongs to the Special Issue Hantaviruses)
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2689 KiB  
Article
The Role of the Coat Protein A-Domain in P22 Bacteriophage Maturation
by David S. Morris and Peter E. Prevelige, Jr.
Viruses 2014, 6(7), 2708-2722; https://doi.org/10.3390/v6072708 - 14 Jul 2014
Cited by 8 | Viewed by 5690
Abstract
Bacteriophage P22 has long been considered a hallmark model for virus assembly and maturation. Repurposing of P22 and other similar virus structures for nanotechnology and nanomedicine has reinvigorated the need to further understand the protein-protein interactions that allow for the assembly, as well [...] Read more.
Bacteriophage P22 has long been considered a hallmark model for virus assembly and maturation. Repurposing of P22 and other similar virus structures for nanotechnology and nanomedicine has reinvigorated the need to further understand the protein-protein interactions that allow for the assembly, as well as the conformational shifts required for maturation. In this work, gp5, the major coat structural protein of P22, has been manipulated in order to examine the mutational effects on procapsid stability and maturation. Insertions to the P22 coat protein A-domain, while widely permissive of procapsid assembly, destabilize the interactions necessary for virus maturation and potentially allow for the tunable adjustment of procapsid stability. Future manipulation of this region of the coat protein subunit can potentially be used to alter the stability of the capsid for controllable disassembly. Full article
(This article belongs to the Special Issue Virus Maturation)
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472 KiB  
Short Communication
Rabbit Hemorrhagic Disease Virus Detected in Pico, Azores, Portugal, Revealed a Unique Endemic Strain with More Than 17 Years of Independent Evolution
by Pedro J. Esteves, Ana M. Lopes, Maria J. Magalhães, Ana Pinheiro, David Gonçalves and Joana Abrantes
Viruses 2014, 6(7), 2698-2707; https://doi.org/10.3390/v6072698 - 14 Jul 2014
Cited by 6 | Viewed by 5756
Abstract
Rabbit hemorrhagic disease is caused by a calicivirus, rabbit hemorrhagic disease virus (RHDV), which is responsible for high mortality in domestic and wild European rabbits (Oryctolagus cuniculus). RHDV strains were sequenced from wild European rabbits (Oryctolagus cuniculus algirus) collected [...] Read more.
Rabbit hemorrhagic disease is caused by a calicivirus, rabbit hemorrhagic disease virus (RHDV), which is responsible for high mortality in domestic and wild European rabbits (Oryctolagus cuniculus). RHDV strains were sequenced from wild European rabbits (Oryctolagus cuniculus algirus) collected in the Azorean island of Pico, Portugal. Phylogenetic analyses showed that the Pico RHDV strains diverge from all of the others described so far, but cluster with the genogroups 1–5 (G1–G5). The genetic distance between the Pico RHDV sequences and each G1, G2 and G3–G5 genogroup (~0.08) is compatible with an RHDV introduction at least 17 years ago. Our results show that in Pico, RHDV is the outcome of an independent evolution from the original RHDV strain that appeared in its European rabbit population. These are the first sequences of RHDV obtained in the subspecies O. c. algirus, outside of its original region, the Iberian Peninsula. Furthermore, we discuss the risk of rabbit translocations from the Azores to the Iberian Peninsula, where the rabbit wild populations are suffering high mortalities. Full article
(This article belongs to the Section Animal Viruses)
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582 KiB  
Meeting Report
Challenges, Progress, and Opportunities: Proceedings of the Filovirus Medical Countermeasures Workshop
by Rona Hirschberg, Lucy A. Ward, Nicole Kilgore, Rebecca Kurnat, Helen Schiltz, Mark T. Albrecht, George W. Christopher and Ed Nuzum
Viruses 2014, 6(7), 2673-2697; https://doi.org/10.3390/v6072673 - 09 Jul 2014
Cited by 29 | Viewed by 8450
Abstract
On August 22–23, 2013, agencies within the United States Department of Defense (DoD) and the Department of Health and Human Services (HHS) sponsored the Filovirus Medical Countermeasures (MCMs) Workshop as an extension of the activities of the Filovirus Animal Non-clinical Group (FANG). The [...] Read more.
On August 22–23, 2013, agencies within the United States Department of Defense (DoD) and the Department of Health and Human Services (HHS) sponsored the Filovirus Medical Countermeasures (MCMs) Workshop as an extension of the activities of the Filovirus Animal Non-clinical Group (FANG). The FANG is a federally-recognized multi-Agency group established in 2011 to coordinate and facilitate U.S. government (USG) efforts to develop filovirus MCMs. The workshop brought together government, academic and industry experts to consider the needs for filovirus MCMs and evaluate the status of the product development pipeline. This report summarizes speaker presentations and highlights progress and challenges remaining in the field. Full article
(This article belongs to the Collection Advances in Ebolavirus, Marburgvirus, and Cuevavirus Research)
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Review
Phages Preying on Bacillus anthracis, Bacillus cereus, and Bacillus thuringiensis: Past, Present and Future
by Annika Gillis and Jacques Mahillon
Viruses 2014, 6(7), 2623-2672; https://doi.org/10.3390/v6072623 - 09 Jul 2014
Cited by 67 | Viewed by 14618
Abstract
Many bacteriophages (phages) have been widely studied due to their major role in virulence evolution of bacterial pathogens. However, less attention has been paid to phages preying on bacteria from the Bacillus cereus group and their contribution to the bacterial genetic pool has [...] Read more.
Many bacteriophages (phages) have been widely studied due to their major role in virulence evolution of bacterial pathogens. However, less attention has been paid to phages preying on bacteria from the Bacillus cereus group and their contribution to the bacterial genetic pool has been disregarded. Therefore, this review brings together the main information for the B. cereus group phages, from their discovery to their modern biotechnological applications. A special focus is given to phages infecting Bacillus anthracis, B. cereus and Bacillus thuringiensis. These phages belong to the Myoviridae, Siphoviridae, Podoviridae and Tectiviridae families. For the sake of clarity, several phage categories have been made according to significant characteristics such as lifestyles and lysogenic states. The main categories comprise the transducing phages, phages with a chromosomal or plasmidial prophage state, γ-like phages and jumbo-phages. The current genomic characterization of some of these phages is also addressed throughout this work and some promising applications are discussed here. Full article
(This article belongs to the Section Bacterial Viruses)
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Article
Characterization of a Proposed Dichorhavirus Associated with the Citrus Leprosis Disease and Analysis of the Host Response
by José Luis Cruz-Jaramillo, Roberto Ruiz-Medrano, Lourdes Rojas-Morales, José Abel López-Buenfil, Oscar Morales-Galván, Claudio Chavarín-Palacio, José Abrahán Ramírez-Pool and Beatriz Xoconostle-Cázares
Viruses 2014, 6(7), 2602-2622; https://doi.org/10.3390/v6072602 - 07 Jul 2014
Cited by 30 | Viewed by 8956
Abstract
The causal agents of Citrus leprosis are viruses; however, extant diagnostic methods to identify them have failed to detect known viruses in orange, mandarin, lime and bitter orange trees with severe leprosis symptoms in Mexico, an important citrus producer. Using high throughput sequencing, [...] Read more.
The causal agents of Citrus leprosis are viruses; however, extant diagnostic methods to identify them have failed to detect known viruses in orange, mandarin, lime and bitter orange trees with severe leprosis symptoms in Mexico, an important citrus producer. Using high throughput sequencing, a virus associated with citrus leprosis was identified, belonging to the proposed Dichorhavirus genus. The virus was termed Citrus Necrotic Spot Virus (CNSV) and contains two negative-strand RNA components; virions accumulate in the cytoplasm and are associated with plasmodesmata—channels interconnecting neighboring cells—suggesting a mode of spread within the plant. The present study provides insights into the nature of this pathogen and the corresponding plant response, which is likely similar to other pathogens that do not spread systemically in plants. Full article
(This article belongs to the Special Issue Plant Viruses)
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2569 KiB  
Review
New Aspects of the Pathogenesis of Canine Distemper Leukoencephalitis
by Charlotte Lempp, Ingo Spitzbarth, Christina Puff, Armend Cana, Kristel Kegler, Somporn Techangamsuwan, Wolfgang Baumgärtner and Frauke Seehusen
Viruses 2014, 6(7), 2571-2601; https://doi.org/10.3390/v6072571 - 02 Jul 2014
Cited by 74 | Viewed by 15583
Abstract
Canine distemper virus (CDV) is a member of the genus morbillivirus, which is known to cause a variety of disorders in dogs including demyelinating leukoencephalitis (CDV-DL). In recent years, substantial progress in understanding the pathogenetic mechanisms of CDV-DL has been made. In vivo [...] Read more.
Canine distemper virus (CDV) is a member of the genus morbillivirus, which is known to cause a variety of disorders in dogs including demyelinating leukoencephalitis (CDV-DL). In recent years, substantial progress in understanding the pathogenetic mechanisms of CDV-DL has been made. In vivo and in vitro investigations provided new insights into its pathogenesis with special emphasis on axon-myelin-glia interaction, potential endogenous mechanisms of regeneration, and astroglial plasticity. CDV-DL is characterized by lesions with a variable degree of demyelination and mononuclear inflammation accompanied by a dysregulated orchestration of cytokines as well as matrix metalloproteinases and their inhibitors. Despite decades of research, several new aspects of the neuropathogenesis of CDV-DL have been described only recently. Early axonal damage seems to represent an initial and progressive lesion in CDV-DL, which interestingly precedes demyelination. Axonopathy may, thus, function as a potential trigger for subsequent disturbed axon-myelin-glia interactions. In particular, the detection of early axonal damage suggests that demyelination is at least in part a secondary event in CDV-DL, thus challenging the dogma of CDV as a purely primary demyelinating disease. Another unexpected finding refers to the appearance of p75 neurotrophin (NTR)-positive bipolar cells during CDV-DL. As p75NTR is a prototype marker for immature Schwann cells, this finding suggests that Schwann cell remyelination might represent a so far underestimated endogenous mechanism of regeneration, though this hypothesis still remains to be proven. Although it is well known that astrocytes represent the major target of CDV infection in CDV-DL, the detection of infected vimentin-positive astrocytes in chronic lesions indicates a crucial role of this cell population in nervous distemper. While glial fibrillary acidic protein represents the characteristic intermediate filament of mature astrocytes, expression of vimentin is generally restricted to immature or reactive astrocytes. Thus, vimentin-positive astrocytes might constitute an important cell population for CDV persistence and spread, as well as lesion progression. In vitro models, such as dissociated glial cell cultures, as well as organotypic brain slice cultures have contributed to a better insight into mechanisms of infection and certain morphological and molecular aspects of CDV-DL. Summarized, recent in vivo and in vitro studies revealed remarkable new aspects of nervous distemper. These new perceptions substantially improved our understanding of the pathogenesis of CDV-DL and might represent new starting points to develop novel treatment strategies. Full article
(This article belongs to the Special Issue Morbillivirus Infections)
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Review
Facing Antibiotic Resistance: Staphylococcus aureus Phages as a Medical Tool
by Zuzanna Kaźmierczak, Andrzej Górski and Krystyna Dąbrowska
Viruses 2014, 6(7), 2551-2570; https://doi.org/10.3390/v6072551 - 01 Jul 2014
Cited by 65 | Viewed by 11146
Abstract
Staphylococcus aureus is a common and often virulent pathogen in humans. This bacterium is widespread, being present on the skin and in the nose of healthy people. Staphylococcus aureus can cause infections with severe outcomes ranging from pustules to sepsis and death. The [...] Read more.
Staphylococcus aureus is a common and often virulent pathogen in humans. This bacterium is widespread, being present on the skin and in the nose of healthy people. Staphylococcus aureus can cause infections with severe outcomes ranging from pustules to sepsis and death. The introduction of antibiotics led to a general belief that the problem of bacterial infections would be solved. Nonetheless, pathogens including staphylococci have evolved mechanisms of drug resistance. Among current attempts to address this problem, phage therapy offers a promising alternative to combat staphylococcal infections. Here, we present an overview of current knowledge on staphylococcal infections and bacteriophages able to kill Staphylococcus, including experimental studies and available data on their clinical use. Full article
(This article belongs to the Section Bacterial Viruses)
760 KiB  
Review
RNA Virus Reverse Genetics and Vaccine Design
by Christopher C. Stobart and Martin L. Moore
Viruses 2014, 6(7), 2531-2550; https://doi.org/10.3390/v6072531 - 25 Jun 2014
Cited by 79 | Viewed by 14353
Abstract
RNA viruses are capable of rapid spread and severe or potentially lethal disease in both animals and humans. The development of reverse genetics systems for manipulation and study of RNA virus genomes has provided platforms for designing and optimizing viral mutants for vaccine [...] Read more.
RNA viruses are capable of rapid spread and severe or potentially lethal disease in both animals and humans. The development of reverse genetics systems for manipulation and study of RNA virus genomes has provided platforms for designing and optimizing viral mutants for vaccine development. Here, we review the impact of RNA virus reverse genetics systems on past and current efforts to design effective and safe viral therapeutics and vaccines. Full article
(This article belongs to the Special Issue Virus-based Vaccines)
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