27 research outputs found
Functional analysis of the Bunyamwera orthobunyavirus Gc glycoprotein
The virion glycoproteins Gn and Gc of Bunyamwera orthobunyavirus (family Bunyaviridae) are encoded by the M RNA genome segment and have roles in both viral attachment and membrane fusion. To investigate further the structure and function of the Gc protein in viral replication, we generated 12 mutants that contain truncations from the N terminus. The effects of these deletions were analysed with regard to Golgi targeting, low pH-dependent membrane fusion, infectious virus-like particle (VLP) formation and virus infectivity. Our results show that the N-terminal half (453 residues) of the Gc ectodomain (909 residues in total) is dispensable for Golgi trafficking and cell fusion. However, deletions in this region resulted in a significant reduction in VLP formation. Four mutant viruses that contained N-terminal deletions in their Gc proteins were rescued, and found to be attenuated to different degrees in BHK-21 cells. Taken together, our data indicate that the N-terminal half of the Gc ectodomain is dispensable for replication in cell culture, whereas the C-terminal half is required to mediate cell fusion. A model for the domain structure of the Gc ectodomain is proposed
Virus nomenclature below the species level : a standardized nomenclature for filovirus strains and variants rescued from cDNA
Specific alterations (mutations, deletions,
insertions) of virus genomes are crucial for the functional
characterization of their regulatory elements and their expression products, as well as a prerequisite for the creation
of attenuated viruses that could serve as vaccine
candidates. Virus genome tailoring can be performed either
by using traditionally cloned genomes as starting materials,
followed by site-directed mutagenesis, or by de novo synthesis
of modified virus genomes or parts thereof. A systematic
nomenclature for such recombinant viruses is
necessary to set them apart from wild-type and laboratoryadapted
viruses, and to improve communication and collaborations
among researchers who may want to use
recombinant viruses or create novel viruses based on them.
A large group of filovirus experts has recently proposed
nomenclatures for natural and laboratory animal-adapted
filoviruses that aim to simplify the retrieval of sequence
data from electronic databases. Here, this work is extended
to include nomenclature for filoviruses obtained in the
laboratory via reverse genetics systems. The previously
developed template for natural filovirus genetic variant
naming,\virus name[(\strain[/)\isolation host-suffix[/
\country of sampling[/\year of sampling[/\genetic
variant designation[-\isolate designation[, is retained, but we propose to adapt the type of information added to each
field for cDNA clone-derived filoviruses. For instance, the
full-length designation of an Ebola virus Kikwit variant
rescued from a plasmid developed at the US Centers for
Disease Control and Prevention could be akin to ‘‘Ebola
virus H.sapiens-rec/COD/1995/Kikwit-abc1’’ (with the
suffix ‘‘rec’’ identifying the recombinant nature of the virus
and ‘‘abc1’’ being a placeholder for any meaningful isolate
designator). Such a full-length designation should be used
in databases and the methods section of publications.
Shortened designations (such as ‘‘EBOV H.sap/COD/95/
Kik-abc1’’) and abbreviations (such as ‘‘EBOV/Kik-abc1’’)
could be used in the remainder of the text, depending on
how critical it is to convey information contained in the
full-length name. ‘‘EBOV’’ would suffice if only one
EBOV strain/variant/isolate is addressed.http://link.springer.com/journal/705hb201
Practical methods for proving program termination
Abstract. We present two algorithms to prove termination of programs by synthesizing linear ranking functions. The first uses an invariant generator based on iterative forward propagation with widening and extracts ranking functions from the generated invariants by manipulating polyhedral cones. It is capable of finding subtle ranking functions which are linear combinations of many program variables, but is limited to programs with few variables. The second, more heuristic, algorithm targets the class of structured programs with single-variable ranking functions. Its invariant generator uses a heuristic extrapolation operator to avoid iterative forward propagation over program loops. For the programs we have considered, this approach converges faster and the invariants it discovers are sufficiently strong to imply the existence of ranking functions
Spillover and pandemic properties of zoonotic viruses with high host plasticity
Most human infectious diseases, especially recently emerging pathogens, originate from animals, and ongoing disease transmission from animals to people presents a significant global health burden. Recognition of the epidemiologic circumstances involved in zoonotic spillover, amplification, and spread of diseases is essential for prioritizing surveillance and predicting future disease emergence risk. We examine the animal hosts and transmission mechanisms involved in spillover of zoonotic viruses to date, and discover that viruses with high host plasticity (i.e. taxonomically and ecologically diverse host range) were more likely to amplify viral spillover by secondary human-to-human transmission and have broader geographic spread. Viruses transmitted to humans during practices that facilitate mixing of diverse animal species had significantly higher host plasticity. Our findings suggest that animal-to-human spillover of new viruses that are capable of infecting diverse host species signal emerging disease events with higher pandemic potential in that these viruses are more likely to amplify by human-to-human transmission with spread on a global scale