Borchers, Andrea T; Chang, Christopher; Gershwin, M Eric; Gershwin, Laurel J
Respiratory syncytial virus (RSV) is amongst the most important pathogenic infections of childhood and is associated with significant morbidity and mortality. Although there have been extensive studies of epidemiology, clinical manifestations, diagnostic techniques, animal models and the immunobiology of infection, there is not yet a convincing and safe vaccine available. The major histopathologic characteristics of RSV infection are acute bronchiolitis, mucosal and submucosal edema, and luminal occlusion by cellular debris of sloughed epithelial cells mixed with macrophages, strands of fibrin, and some mucin. There is a single RSV serotype with two major antigenic subgroups, A and B. Strains of both subtypes often co-circulate, but usually one subtype predominates. In temperate climates, RSV infections reflect a distinct seasonality with onset in late fall or early winter. It is believed that most children will experience at least one RSV infection by the age of 2 years. There are several key animal models of RSV. These include a model in mice and, more importantly, a bovine model; the latter reflects distinct similarity to the human disease. Importantly, the prevalence of asthma is significantly higher amongst children who are hospitalized with RSV in infancy or early childhood. However, there have been only limited investigations of candidate genes that have the potential to explain this increase in susceptibility. An atopic predisposition appears to predispose to subsequent development of asthma and it is likely that subsequent development of asthma is secondary to the pathogenic inflammatory response involving cytokines, chemokines and their cognate receptors. Numerous approaches to the development of RSV vaccines are being evaluated, as are the use of newer antiviral agents to mitigate disease. There is also significant attention being placed on the potential impact of co-infection and defining the natural history of RSV. Clearly, more research is required to define the relationships between RSV bronchiolitis, other viral induced inflammatory responses, and asthma.
Nipah virus, a newly emerging deadly paramyxovirus isolated during a large outbreak of viral encephalitis in Malaysia, has many of the physical attributes to serve as a potential agent of bioterrorism. The outbreak caused widespread panic and fear because of its high mortality and the inability to control the disease initially. There were considerable social disruptions and tremendous economic loss to an important pig-rearing industry. This highly virulent virus, believed to be introduced into pig farms by fruit bats, spread easily among pigs and was transmitted to humans who came into close contact with infected animals. From pigs, the virus was also transmitted to other animals such as dogs, cats, and horses. The Nipah virus has the potential to be considered an agent of bioterrorism.
Tahir, Muhammad; Amin, Imran; Haider, Muhammad Saleem; Mansoor, Shahid; Briddon, Rob W
Samples of two Ageratum conyzoides, one Sonchus oleraceus and one turnip (Brassica rapa var. rapa) exhibiting virus-like symptoms were collected from Pakistan and Nepal. Full-length begomovirus clones were obtained from the four plant samples and betasatellite clones from three of these. The begomovirus sequences were shown to be isolates of Ageratum enation virus (AEV) with greater than 89.1% nucleotide sequence identity to the 26 AEV sequences available in the databases. The three betasatellite sequences were shown to be isolates of Ageratum yellow leaf curl betasatellite (AYLCB) with greater than 90% identity to the 18 AYLCB sequences available in the databases. The AEV sequences were shown to fall into two distinct strains, for which the names Nepal (consisting of isolates from Nepal, India, and Pakistan-including the isolates identified here) and India (isolates occurring only in India) strains are proposed. For the clones obtained from two AEV isolates, with their AYLCB, infectivity was shown by Agrobacterium-mediated inoculation to Nicotiana benthamiana, N. tabacum, Solanum lycopersicon and A. conyzoides. N. benthamiana plants infected with AEV alone or betasatellite alone showed no symptoms. N. benthamiana plants infected with AEV with its associated betasatellite showed leaf curl symptoms. The findings show that AEV is predominantly a virus of weeds that has the capacity to infect crops. AYLCB appears to be the common partner betasatellite of AEV and is associated with diseases with a range of very different symptoms in the same plant species. The inability to satisfy Koch's postulates with the cloned components of isolate SOL in A. conyzoides suggests that the etiology may be more complex than a single virus with a single betasatellite.
Knight, Alan L; Witzgall, Peter
The combination of a pathogenic virus and mutualistic yeasts isolated from larvae of codling moth Cydia pomonella is proposed as a novel insect control technique. Apples were treated with codling moth granulovirus (CpGV) and either one of three yeasts, Metschnikowia pulcherrima, Cryptococcus tephrensis, or Aureobasidium pullulans. The combination of yeasts with CpGV significantly increased mortality of neonate codling moth larvae, compared with CpGV alone. The three yeasts were equally efficient in enhancing the activity of CpGV. The addition of brown cane sugar to yeast further increased larval mortality and the protection of fruit against larvae. In comparison, without yeast, the addition of sugar to CpGV did not produce a significant effect. A field trial confirmed that fruit injury and larval survival were significantly reduced when apple trees were sprayed with CpGV, M. pulcherrima, and sugar. We have shown earlier that mutualistic yeasts are an essential part of codling moth larval diet. The finding that yeast also enhances larval ingestion of an insect-pathogenic virus is an opportunity for the development of a novel plant protection technique. We expect the combination of yeasts and insect pathogens to essentially contribute to future insect management.
Harder, T C; Osterhaus, A D
Canine distemper morbillivirus (CDV) induces a multisystemic, often fatal disease in a wide and seemingly expanding host range among the Carnivora. Several genotypes of an otherwise monotypic virus species co-circulate in a geographically restricted pattern. Interspecies transmissions frequently occur, often leading to devastating epizootics in highly susceptible or immunologically naive populations.
Zhao, Jianjun; Yan, Xijun; Wu, Wei
Canine distemper (CD) caused by Canine distemper virus (CDV) was first reported in 1905, and has been one of the most serious contagious diseases of dogs as well as other carnivores. Recently, increasing cases of canine distemper (CD) both in vaccinated and unvaccinated dogs and in wildlife have been reported in Japan, America, Europe and Africa. Based on phylogenetic analysis of the hemagglutinin (H) gene sequences, six genotypes of CDV were distinguished. Antigenic heterogeneity of the H protein that provides an important protective antigen against CDV infection has been observed between wild-type CDV and vaccine strains. So it was suspected that the vaccines currently used can no longer efficiently protect animal from present-day circulating CDV infection. The host range of CDV includes all species of the families Canidae and many other species. Both signaling lymphocyte activation molecule (SLAM) and heparin sulfate (HS) expressed on the cells of the immune system or other non-lymphoid tissues can act as the cellular receptors for CDV, and are one of the major determinants of the host range and tissue tropism. In this review, we discussed the above-mentioned issues based on the recent research progress and the studies in our laboratory.
Doss, Mona; Ruchala, Piotr; Tecle, Tesfaldet; Gantz, Donald; Verma, Anamika; Hartshorn, Alex; Crouch, Erika C.; Luong, Hai; Micewicz, Ewa D.; Lehrer, Robert I.; Hartshorn, Kevan L.
θ-defensins are cyclic octadecapeptides found in non-human primates whose broad antiviral-spectrum includes HIV-1, HSV-1, SARS, and influenza A virus (IAV). We previously reported that synthetic θ-defensins called retrocyclins can neutralize and aggregate various strains of IAV and increase IAV uptake by neutrophils. This report describes two families of peptides, hapivirins (HpVs) and diprovirins (DpVs), whose design was inspired by retrocyclins. The goal was to develop smaller partially cyclic peptides that retain the antiviral activity of retrocyclins, while being easier to synthesize. The novel peptides also allowed for systemic substitution of key residues to evaluate the role of charge or hydrophobicity on antiviral activity. Seventy-two HpV or DpV peptides are described in this report, including several whose anti-IAV activity equals or exceeds that of normal α– or θ-defensins. Some of these also had strong antibacterial and antifungal activity. These new peptides were active against H3N2 and H1N1 strains of IAV. Structural features imparting strong antiviral activity were identified through iterative cycles of synthesis and testing. Our findings show the importance of hydrophobic residues for antiviral activity and show that pegylation, which often increases a peptide’s serum half-life in vivo, can increase the antiviral activity of DpVs. The new peptides acted at an early phase of viral infection and when combined with pulmonary surfactant protein D, their antiviral effects were additive. The peptides strongly increased neutrophil and macrophage uptake of IAV, while inhibiting monocyte cytokine generation. Development of modified θ– defensin analogues provides an approach for creating novel antiviral agents for IAV infections. PMID:22345650
Sivalingam, P N; Satheesh, V; John, P; Chandramohan, S; Malathi, V G
Clerodendron inerme, a common hedge plant grown in India, is affected by a yellow mosaic disease caused by a begomovirus. In the present study, the complete genome (DNA A) of this virus was cloned and sequenced. The total size of DNA A is 2760 nucleotides. The genome of this virus contains six open reading frames and a non-coding intergenic region of 293 nucleotides. Nucleotide sequence comparison analysis revealed maximum sequence identity with Papaya leaf curl virus-Pakistan [Pakistan:Cotton:2002] (73.9%). As this virus had less than 89% identity with other begomoviruses, it was identified as a new begomovirus species and tentatively, named as Clerodendron yellow mosaic virus-[India:New Delhi:2007] (ClYMV-[IN:ND:07]).
Moss, Walter N; Steitz, Joan A
This review covers several computational methods for discovering structured non-coding RNAs in viruses and modeling their putative secondary structures. Here we will use examples from two target viruses to highlight these approaches: influenza A virus-a relatively small, segmented RNA virus; and Epstein-Barr virus-a relatively large DNA virus with a complex transcriptome. Each system has unique challenges to overcome and unique characteristics to exploit. From these particular cases, generically useful approaches can be derived for the study of additional viral targets.
A biodegradable and controlled drug delivery system has been developed herein composed of electrospun polymeric nanofibers impregnated with cargo loaded Red clover necrotic mosaic virus (RCNMV)---a robust plant virus---as the drug carrier nanoparticle. In this system, controlled drug release is achieved by altering the porosity of the biodegradable matrix as well as controlling the position and distribution of the cargo loaded nanocarriers in the matrix. Solution electrospinning as well as dipping method are used to create and to impregnate the matrix (the fibers of which possess uniformly distributed nano-size surface pores) with cargo loaded nanocarriers. Prior to the impregnation stage of cargo loaded nanocarriers into the matrix, compatibility of a group of candidate cargos (Ampicillin, Novanthrone, Doxorubicin and Ethidium Bromide) and RCNMV functionality with potential electrospinning solvents were investigated and a solvent with the least degradative effect was selected. In order to achieve both sustained and immediate drug release profiles, cargo loaded nanocarriers were embedded into the matrix---through co-spinning process---as well as on the surface of matrix fibers---through dipping method. SEM, TEM and Fluorescent Light Microscopy images of the medicated structures suggested that the nanocarriers were incorporated into/on the matrix. In vitro release assays were also carried out the results of which confirmed having obtained sustained release in the co-spun medicated structures where as dipped samples showed an immediate release profile.
Touloudi, A.; Valiakos, G.; Athanasiou, L. V.; Birtsas, P.; Giannakopoulos, A.; Papaspyropoulos, K.; Kalaitzis, C.; Sokos, C.; Tsokana, C. N.; Spyrou, V.; Petrovska, L.; Billinis, C.
Objectives Serum samples, collected from 94 European wild boar (Sus scrofa) during the hunting seasons 2006 -2010 from different regions of Greece, were examined in order to estimate the role of these wildlife species as reservoir of pathogens important for livestock and/or public health. Materials and Methods The assays used for this purpose were commercial indirect ELISA for the detection of antibodies against porcine circovirus type 2 (PCV-2), porcine reproductive and respiratory syndrome (virus) (PRRSV), Aujeszky's disease virus (ADV), influenza A (IA) virus, Actinobacillus pleuropneumoniae, Mycoplasma hyopneumoniae, Salmonella species, Trichinella species and indirect immunofluorescence antibody test for the detection of antibodies against Toxoplasma gondii and Neospora caninum. Results Antibodies against PCV-2, PRRSV, ADV, IA virus,A. pleuropneumoniae, M. hyopneumoniae,Salmonella species, Trichinella species, T. gondii and N. caninum were detected in 19.1 per cent, 12.8 per cent, 35.1 per cent, 1.1 per cent, 57.4 per cent, 0 per cent, 4.3 per cent, 6.4 per cent, 5.2 per cent and 1.1 per cent of the samples, respectively. Cluster analysis revealed a hot spot of seropositivity near Bulgarian border; seropositivity to ADV was more common among female animals. Conclusions These results indicate exposure of wild boar to most of the above-mentioned pathogens, raising concern about the possibility that these species may pose a significant health risk for livestock and/or humans. PMID:26392908
Baccala, Roberto; Welch, Megan J; Gonzalez-Quintial, Rosana; Walsh, Kevin B; Teijaro, John R; Nguyen, Anthony; Ng, Cherie T; Sullivan, Brian M; Zarpellon, Alessandro; Ruggeri, Zaverio M; de la Torre, Juan Carlos; Theofilopoulos, Argyrios N; Oldstone, Michael B A
The outcome of a viral infection reflects the balance between virus virulence and host susceptibility. The clone 13 (Cl13) variant of lymphocytic choriomeningitis virus--a prototype of Old World arenaviruses closely related to Lassa fever virus--elicits in C57BL/6 and BALB/c mice abundant negative immunoregulatory molecules, associated with T-cell exhaustion, negligible T-cell-mediated injury, and high virus titers that persist. Conversely, here we report that in NZB mice, despite the efficient induction of immunoregulatory molecules and high viremia, Cl13 generated a robust cytotoxic T-cell response, resulting in thrombocytopenia, pulmonary endothelial cell loss, vascular leakage, and death within 6-8 d. These pathogenic events required type I IFN (IFN-I) signaling on nonhematopoietic cells and were completely abrogated by IFN-I receptor blockade. Thus, IFN-I may play a prominent role in hemorrhagic fevers and other acute virus infections associated with severe vascular pathology, and targeting IFN-I or downstream effector molecules may be an effective therapeutic approach.
Chen, Weiqiang; Foo, Suan-Sin; Zaid, Ali; Teng, Terk-Shin; Herrero, Lara J; Wolf, Stefan; Tharmarajah, Kothila; Vu, Luan D; van Vreden, Caryn; Taylor, Adam; Freitas, Joseph R; Li, Rachel W; Woodruff, Trent M; Gordon, Richard; Ojcius, David M; Nakaya, Helder I; Kanneganti, Thirumala-Devi; O'Neill, Luke A J; Robertson, Avril A B; King, Nicholas J; Suhrbier, Andreas; Cooper, Matthew A; Ng, Lisa F P; Mahalingam, Suresh
Mosquito-borne viruses can cause severe inflammatory diseases and there are limited therapeutic solutions targeted specifically at virus-induced inflammation. Chikungunya virus (CHIKV), a re-emerging alphavirus responsible for several outbreaks worldwide in the past decade, causes debilitating joint inflammation and severe pain. Here, we show that CHIKV infection activates the NLRP3 inflammasome in humans and mice. Peripheral blood mononuclear cells isolated from CHIKV-infected patients showed elevated NLRP3, caspase-1 and interleukin-18 messenger RNA expression and, using a mouse model of CHIKV infection, we found that high NLRP3 expression was associated with peak inflammatory symptoms. Inhibition of NLRP3 activation using the small-molecule inhibitor MCC950 resulted in reduced CHIKV-induced inflammation and abrogated osteoclastogenic bone loss and myositis, but did not affect in vivo viral replication. Mice treated with MCC950 displayed lower expression levels of the cytokines interleukin-6, chemokine ligand 2 and tumour necrosis factor in joint tissue. Interestingly, MCC950 treatment abrogated disease signs in mice infected with a related arthritogenic alphavirus, Ross River virus, but not in mice infected with West Nile virus-a flavivirus. Here, using mouse models of alphavirus-induced musculoskeletal disease, we demonstrate that NLRP3 inhibition in vivo can reduce inflammatory pathology and that further development of therapeutic solutions targeting inflammasome function could help treat arboviral diseases.Chikungunya virus infection leads to painful arthritis-like joint inflammation. This study shows that the NLRP3 inflammasome is crucial for alphavirus-induced inflammation and its inhibition is an effective therapeutic strategy.
Palanga, Essowè; Filloux, Denis; Martin, Darren P; Fernandez, Emmanuel; Gargani, Daniel; Ferdinand, Romain; Zabré, Jean; Bouda, Zakaria; Neya, James Bouma; Sawadogo, Mahamadou; Traore, Oumar; Peterschmitt, Michel; Roumagnac, Philippe
Cowpea, (Vigna unguiculata L. (Walp)) is an annual tropical grain legume. Often referred to as "poor man's meat", cowpea is one of the most important subsistence legumes cultivated in West Africa due to the high protein content of its seeds. However, African cowpea production can be seriously constrained by viral diseases that reduce yields. While twelve cowpea-infecting viruses have been reported from Africa, only three of these have so-far been reported from Burkina Faso. Here we use a virion-associated nucleic acids (VANA)-based metagenomics method to screen for the presence of cowpea viruses from plants collected from the three agro-climatic zones of Burkina Faso. Besides the three cowpea-infecting virus species which have previously been reported from Burkina Faso (Cowpea aphid borne mosaic virus [Family Potyviridae], the Blackeye cowpea mosaic virus-a strain of Bean common mosaic virus-[Family Potyviridae] and Cowpea mottle virus [Family Tombusviridae]) five additional viruses were identified: Southern cowpea mosaic virus (Sobemovirus genus), two previously uncharacterised polerovirus-like species (Family Luteoviridae), a previously uncharacterised tombusvirus-like species (Family Tombusviridae) and a previously uncharacterised mycotymovirus-like species (Family Tymoviridae). Overall, potyviruses were the most prevalent cowpea viruses (detected in 65.5% of samples) and the Southern Sudan zone of Burkina Faso was found to harbour the greatest degrees of viral diversity and viral prevalence. Partial genome sequences of the two novel polerovirus-like and tombusvirus-like species were determined and RT-PCR primers were designed for use in Burkina Faso to routinely detect all of these cowpea-associated viruses.