Hendra and Nipah viruses: different and dangerous

Hendra virus and Nipah virus are highly pathogenic paramyxoviruses that have recently emerged from flying foxes to cause serious disease outbreaks in humans and livestock in Australia, Malaysia, Singapore and Bangladesh. Their unique genetic constitution, high virulence and wide host range set them apart from other paramyxoviruses. These features led to their classification into the new genus Henipavirus within the family Paramyxoviridae and to their designation as Biosafety Level 4 pathogens. This review provides an overview of henipaviruses and the types of infection they cause, and describes how studies on the structure and function of henipavirus proteins expressed from cloned genes have provided insights into the unique biological properties of these emerging human pathogens.     

Related haloarchaeal pleomorphic viruses contain different genome types

Archaeal viruses have been the subject of recent interest due to the diversity discovered in their virion architectures. Recently, a new group of haloarchaeal pleomorphic viruses has been discovered. It is distinctive in terms of the virion morphology and different genome types (ssDNA/dsDNA) harboured by rather closely related representatives. To date there are seven isolated viruses belonging to this group. Most of these share a cluster of five conserved genes, two of which encode major structural proteins. Putative proviruses and proviral remnants containing homologues of the conserved gene cluster were also identified suggesting a long-standing relationship of these viruses with their hosts. Comparative genomic analysis revealed three different ways of the genome organization, which possibly reflect different replication strategies employed by these viruses. The dsDNA genomes of two of these viruses were shown to contain single-strand interruptions. Further studies on one of the genomes suggested that the interruptions are located along the genome in a sequence-specific manner and exhibit polarity in distribution.     

Quasispecies spatial models for RNA viruses with different replication modes and infection strategies

Empirical observations and theoretical studies suggest that viruses may use different replication strategies to amplify their genomes, which impact the dynamics of mutation accumulation in viral populations and therefore, their fitness and virulence. Similarly, during natural infections, viruses replicate and infect cells that are rarely in suspension but spatially organized. Surprisingly, most quasispecies models of virus replication have ignored these two phenomena. In order to study these two viral characteristics, we have developed stochastic cellular automata models that simulate two different modes of replication (geometric vs stamping machine) for quasispecies replicating and spreading on a two-dimensional space. Furthermore, we explored these two replication models considering epistatic fitness landscapes (antagonistic vs synergistic) and different scenarios for cell-to-cell spread, one with free superinfection and another with superinfection inhibition. We found that the master sequences for populations replicating geometrically and with antagonistic fitness effects vanished at low critical mutation rates. By contrast, the highest critical mutation rate was observed for populations replicating geometrically but with a synergistic fitness landscape. Our simulations also showed that for stamping machine replication and antagonistic epistasis, a combination that appears to be common among plant viruses, populations further increased their robustness by inhibiting superinfection. We have also shown that the mode of replication strongly influenced the linkage between viral loci, which rapidly reached linkage equilibrium at increasing mutations for geometric replication. We also found that the strategy that minimized the time required to spread over the whole space was the stamping machine with antagonistic epistasis among mutations. Finally, our simulations revealed that the multiplicity of infection fluctuated but generically increased along time.     

Fate of 130 hemagglutinins from different influenza A viruses

In this study, we use our probabilistic models to analyze 130 hemagglutinins from different influenza A virus in order to gain the insight into their fate. The results provide three lines of evidence regarding the H5, H6, and H9 hemagglutinins: (i) the H5 hemagglutinins are more sensitive to mutations, this is the current state of the H5, H6, and H9 hemagglutinins; (ii) the H5 hemagglutinins had experienced more mutations in the past, this is the history of the H5, H6, and H9 hemagglutinins; and (iii) the H6 hemagglutinins has a bigger potential towards future mutations, this is the future of the H5, H6, and H9 hemagglutinins. Furthermore, this study gives two clues on the mutation tendency that is a degeneration process and the species susceptibility that is the chickens and ducks.     

Fluorosugars inhibit biological properties of different enveloped viruses.

Both 2-deoxy-2-fluoro-D-glucose and 2-deoxy-2-fluoro-D-mannose were found to be potent inhibitors of the synthesis of infectious Semliki forest and fowl plague virus in chicken embryo cells and also of pseudorabies virus grown in rabbit kidney cells. It was found that the pseudorabies virus-mediated cell fusion and the synthesis of functional hemagglutinin of fowl plague virus were blocked. In all cases the 2-deoxy-2-fluoro-D-mannose-caused inhibition was stronger than the 2-deoxy-2-fluoro-D-glucose- or 2-deoxy-D-glucose-mediated blocks. Studies on the virus-specified proteins from Semiliki forest virus-infected cells grown in the presence of the inhibitors show that the target of the fluorosugar action, parallel to the well-studied effects of 2-deoxy-D-glucose, is the glycoprotein biosynthesis.     

Thermal stability of structurally different viruses with proven or potential relevance to food safety

Aims: To collect comparative data on thermal stability of structurally different viruses with proven or potential relevance to food safety. Methods and Results: Suspensions with poliovirus Sabin1, adenovirus type5, parechovirus1, human norovirus (NoV) GII.4, murine NoV (MNV1) and human influenza A (H1N1) viruses were heated at 56 and 73°C. Infectivity was tested by culture assay for all but human NoV GII.4 that cannot be cultivated in vitro. Time to first log₁₀ reduction (TFL‐value) was calculated based on best fit using the monophasic, biphasic or Weibull models. The Weibull model provided the best fit at 56°C for all viruses except influenza virus. The TFL at 56°C varied between a high of 27 min (parechovirus) to a low of 10 s (adenovirus) and ranked parechovirus > influenza > MNV1 > poliovirus > adenovirus. The monophasic model best described the behaviour of the viruses at 73°C, in which case the TFL was MNV1(62s) > influenza > adenovirus > parechovirus > poliovirus(14s). Conclusions: Viruses do not follow log‐linear thermal inactivation kinetics and the thermostability of parechovirus and influenza virus is similar to that of proven foodborne viruses. Significance and Impact of the Study: Resistant fractions of viruses may remain infectious in thermal inactivation processes and inactivation of newly discovered or enveloped viruses in thermal food preparation processes should not be assumed without further testing.     

MDCK cell-cultured influenza virus vaccine protects mice from lethal challenge with different influenza viruses

Influenza epidemics are major health concern worldwide. Vaccination is the major strategy to protect the general population from a pandemic. Currently, most influenza vaccines are manufactured using chicken embroynated eggs, but this manufacturing method has potential limitations, and cell-based vaccines offer a number of advantages over the traditional method. We reported here using the scalable bioreactor to produce pandemic influenza virus vaccine in a Madin-Darby canine kidney cell culture system. In the 7.5-L bioreactor, the cell concentration reached to 3.2 × 10(6) cells/mL and the highest virus titers of 256 HAU/50 μL and 1 × 10(7) TCID50/mL. The HA concentration was found to be 11.2 μg/mL. The vaccines produced by the cell-cultured system induced neutralization antibodies, cross-reactive T-cell responses, and were protective in a mouse model against different lethal influenza virus challenge. These data indicate that microcarrier-based cell-cultured influenza virus vaccine manufacture system in scalable bioreactor could be used to produce effective pandemic influenza virus vaccines.     

Monoclonal antibodies with specificity for three different serotypes of Marek's disease viruses in chickens

A total of 50 antibody-secreting hybridoma cells against Marek's disease virus (MDV) and turkey herpesvirus (HVT) have been produced. Eleven hybridomas were used for serotyping a panel of 15 pathogenic and nonpathogenic strains of MDV and HVT, representing three serotypes. The antibodies from the culture medium have fluorescence antibody (FA) titers of up to 100 and those from mouse ascitic fluid have titers ranging from 10(4) to 10(6). Monoclonal antibody T81 is type-common, i.e., it reacts at equal titer with all MDV and HVT tested. Of the remaining 10 antibodies, eight react only with pathogenic and attenuated strains of MDV (presumably serotype 1), one reacts only with nonpathogenic MDV (presumably) serotype 2), and one reacts only with strains of HVT (presumably serotype 3). Two hybridomas belong to IgG2a and IgG2b subclasses, respectively, and the remaining nine belong to IgG1 subclass. None of the antibodies specific for MDV strains reacted with homologous viruses in serum neutralization (SN), agar gel precipitin (AGP), or membrane immunofluorescence tests. Antibody L78, which is specific for HVT, was reactive with its homologous virus in the SN test; antibody from the culture medium showed an SN titer of 10 and that from mouse ascites a titer of 10,000. None of the antibodies specific for MDV or HVT reacted with other avian or mammalian herpesviruses, avian leukosis viruses (ALV), reticuloendotheliosis viruses (REV), or Marek's disease tumor-associated surface antigen (MATSA) expressed in a lymphoblastoid cell line, MDCC-MSB-1.     

Spread of infection with hepatitis B and C viruses in different population groups of north-western Ukraine

The detection rate of specific markers of hepatitides B and C among the child and adult population, including 487 children in 5 boarding schools, 338 oncological, hematological, urological patients and 206 medical staff members in Rovno and the Rovno region (North-Western Ukraine), was determined. In boarding-school the markers of HB (HBsAg, anti-HBs, summary anti-HBc) were detected 3.5 times more often than among the child population in general (in 28.3 and 8.0% respectively). In children staying in a boarding school for up to 1 year (126 children) these markers were determined in 23% of cases, and in those who stayed there for 3-5 years, in 58.1% of cases. Among the members of the groups where children with HBsAg were found the markers of HB occurred 3.3 more often then among the children in the groups having no HBsAg carriers (45.3 and 13.9% respectively). The detection rates of the markers of HB in children with various kinds of C.N.S. pathology (first of all, with mongolism) and without concomitant diseases were sharply different (they were found, respectively, in 52.9 and 19.6%, including HBsAg in 17.4 and 2.7%). At the same time the detection rate of anti-HCV among boarding-school children (including those with C.N.S. lesions) was no different from that among the child population in general, which was indicative of great differences in the activity of the nonartificial transmission routes HB and HC viruses. Patients with oncological, hematological and urological diseases who had great "parenteral load", as well as medical staff members, formed a high risk group for being infected with both HB and HC viruses.     

Precipitation of S,M, X and Y potato viruses by polyethyleneglycols with different molecular weights

The minimum concentration of polyethyleneglycol (PEG) with molecular weights 4000, 6000, and 15000 necessary for precipitation of S, M, X and Y potato viruses was determined. An excessive amount of PEG causes the precipitation of other protein compounds from potato leaf cell sap. In order to obtain highly purified samples, it is necessary to use just the minimum sufficient amount of PEG. Using the minimum quantity of PEG is, also, advisable from an economical point of view. The minimum concentration of PEG of given molecular weight differs for different potato disease viruses. The concentration of PEG necessary for precipitation of a given potato virus depends on the molecular weight of PEG used—4000, 6000 and 15000. As the molecular weight increases, the concentration of PEG necessary for precipitation decreases.