Special Issue "Feature Papers"
Deadline for manuscript submissions: closed (28 February 2014)
Manuscript Submission Information
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The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.
Type of Paper: Review
Title: Structural Differences Observed in Mammalian and Insect Arboviruses
Authors: Raquel Hernandez et al.
Abstract: Arthropod borne viruses have developed a complex life cycle during which insects vector the virus between a virus reservoir and a mammalian host. These arthropod borne viruses belong to the families Togaviridae, Flaviviridae and Bunyaviridae. This group of viruses contains many pathogens which cause febrile, hemorrhagic and encephalitic disease or arthritic symptoms which can be persistent. While it was known that these viruses were of a hybrid nature, containing the RNA and proteins specified by the virus genome in the context of the host derived membrane and carrying the host encoded glycosylation it was assumed that the structures from both hosts were equivalent. It had been appreciated for many years that the genome of these viruses had to adapt evolutionarily to be able to encode sequence information which was relevant to both the cellular metabolisms of such divergent phyla as insect and mammals, yet displaying another form of crossbreed. From a structural perspective these virus particles are macromolecular motors adapted in design to assemble into a packaging and delivery system for the virus genome, and only when associated with the conditions appropriate for a productive infection to disassemble and deliver the cargo (Hernandez, Paredes et al. 2008; Brown and Hernandez 2012). In the paper by He et. al. (He, Piper et al. 2010) we used small angle neutron scattering to explore the nature of Sindbis virus (alphavirus) particles produced by mammalian and insect. The findings were significantly distinct from what was expected because virus particles from these two hosts had important differences. It was determined that while the radial position of the lipid bilayer did not change significantly, it was possible to conclude that the membrane did have more cholesterol when the virus was grown in mammalian cells than insect cells. This property has been shown to effect the virus stability (Hafer, Whittlesey et al. 2009). Additionally, the outer protein shell was found to be more extended in the mammalian Sindbis virus than that of the insect virus. The SANS data also demonstrated that the RNA and nucleocapsid protein share a closer interaction in the mammalian cell grown virus than in the virus from the insect host. The biological consequences of the structural differences uncovered by this new technique are not known. It has been proposed that for dengue virus (flavivirus) the difference displayed by the insect virus, which is assembled at ambient temperature allows it to expand when exposed to human body temperature, 37 C (Fibriansah, Ng et al. 2013; Zhang, Sheng et al. 2013). Both these studies speculated that the change in structure may affect the response of the mammalian host by revealing preciously unexposed epitopes. However, these changes will only be exposed to the host for one round of replication, after which the second structure will be adopted. However, viruses from both hosts represent metastable structural intermediates primed for infection and these two distinct infectious intermediates may represent the optimal for of the structure from its distinct host environment. More work is required to fully appreciate these intricate structures.
Brown, D. T. and R. Hernandez (2012). "Infection of cells by alphaviruses." Adv Exp Med Biol 726: 181-199.
Fibriansah, G., T.-S. Ng, et al. (2013). "Structural changes of dengue virus when exposed to 37°C." Journal of Virology.
Hafer, A., R. Whittlesey, et al. (2009). "Differential incorporation of cholesterol by Sindbis virus grown in mammalian or insect cells." J Virol 83(18): 9113-9121.
He, L., A. Piper, et al. (2010). "The structure of Sindbis virus produced from vertebrate and invertebrate hosts as determined by small-angle neutron scattering." J Virol 84(10): 5270-5276.
Hernandez, R., A. Paredes, et al. (2008). "Sindbis virus conformational changes induced by a neutralizing anti-E1 monoclonal antibody." J Virol 82(12): 5750-5760.
Zhang, X., J. Sheng, et al. (2013). "Dengue structure differs at the temperatures of its human and mosquito hosts." Proceedings of the National Academy of Sciences 110(17): 6795-6799.
Type of Paper: Review
Title: A New Group of Flaviviruses Only Detected in Insects
Author: Mattia Calzolari
Affiliation: Laboratorio Entomologia Sanitaria, Istituto Zooprofilattico Sperimentale della Lombardia e dell'Emilia Romagna "B. Ubertini", Sezione di Reggio Emilia, via Pitagora 2, 42100 Reggio Emilia, Italy
Abstract: Different flaviviruses are important pathogens for human and animals (dengue viruses, Japanese encephalitis virus, West Nile virus), but an increasing number of related virus without a known pathogenic capacity, was isolated worldwide and tentatively ascribed to Flavivirus genera. Phylogenetic studies shown that genomic sequences of these viruses diverge from other flaviviruses, moreover these viruses seem to be exclusive of insect (they don’t grow on vertebrate cell line) and were already defined mosquito-only flaviviruses or insect-specific flaviviruses. At least nine of these viruses were isolated worldwide; some of them were isolated in different continents or were detected in several mosquito species. But large part of the cycle of these viruses is not well know, for instance their persistence mechanism in the environment is not clear. The wide distribution and the continuous detections of these viruses raise interesting issues on the possible interactions with the pathogenic flavivirus and on the influence on bionomics of their arthropod hosts.
Type of Paper: Article
Title: Baculovirus-derived Human Vaccines
Authors: Miriam Klausberger1 and Florian Krammer2#
Affiliations: 1 Vienna Institute of Biotechnology, University of Natural Resources and Life Sciences, Vienna, Austria; 2 Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, USA; # To whom correspondence should be addressed: Florian Krammer, firstname.lastname@example.org
Abstract: Baculoviruses are large, enveloped double stranded DNA virus that infect diverse species of Lepidoptera. Their large DNA genome can easily be manipulate and allows for stable insertion of genes of interest which can be expressed by strong viral promoters. Baculoviruses are considered safe for humans and the insect cell expression system allows for the expression of proteins with complex structure and mammalian-like post-translational modifications in large quantities. Due to this features the baculovirus expression system is becoming increasingly popular for the expression of human vaccines. Two human vaccines, targeting human papilloma virus and cancer, have been approved in recent years. In 2013 a third vaccine, targeting influenza virus, was licensed for use in humans in the US. Many other baculovirus derived vaccines are currently in pre-clinical and clinical development. It is expected that many of these products appear on the market in the coming years.