Publications

Foot-and-mouth disease (FMD) is endemic in mainland Southeast Asia where up to seven genetically distinct viral lineages co-circulate (O/SEA/Mya-98, O/SEA/Cam-94, O/ME-SA/PanAsia, O/ME-SA/PanAsia-2, O/CATHAY, A/ASIA/Sea-97, and serotype Asia 1). The aim of this study was to analyse the sequence variability between representative complete genomes for these seven lineages. The genome sequences varied from 8130 to 8192 nucleotides in length and shared nucleotide identities ranging from 91.8 to 78.9%. Broad-scale differences such as block and codon deletions observed in these genomes paralleled features that have been reported previously for other FMDV sequences from Southeast Asia. Comparison between these sequences revealed the presence of 2501 variant sites which were more evident in regions encoding surface capsid proteins (VP2, VP3 and VP1) compared to regions encoding non-structural proteins. Specific comparisons between closely related O/ME-SA sequences showed that the distribution of variant sites was focussed particularly at the 5' end of the genome indicating that recombination may have occurred during the evolution of the O/ME-SA/PanAsia-2 lineage. These sequences provide insights into the evolutionary mechanisms by which new lineages generate genetic and antigenic novelty in the region and will form the basis of studies to define the spatio-temporal epidemiology of FMDV.

Experimental autoimmune encephalomyelitis (EAE), a well-established model of multiple sclerosis, is characterised by microglial activation and lymphocyte infiltration. Induction of EAE in Lewis rats produces an acute monophasic disease characterised by a single peak of disability followed by a spontaneous and complete recovery and a subsequent tolerance to further immunizations. In the current study we have performed a detailed analysis of the dynamics of different lymphocyte populations and cytokine profile along the induction, peak, recovery and post-recovery phases in this paradigm. MBP-injected rats were sacrificed attending exclusively to their clinical score, and the different populations of T-lymphocytes as well as the dynamics of different pro-and anti-inflammatory cytokines were analysed in the spinal cord by flow cytometry, immunohistochemistry and ELISA. Our results revealed that, during the induction and peak phases, in parallel to an increase in symptomatology, the number of CD3+ and CD4+ cells increased progressively, showing a Th1 phenotype, but unexpectedly during recovery, although clinical signs progressively decreased, the number and proportion of CD3+ and CD4+ populations remained unaltered. Interestingly, during this recovery phase, we observed a marked decrease of Th1 and an important increase in Th17 and T-reg cells. Moreover, our results indicate a specific cytokine expression profile along the EAE course characterized by no changes of IL10 and IL17 levels, decrease of IL21 on the peak, and high IL22 levels during the induction and peak phases that markedly decrease during recovery. In summary, these results revealed the existence of a specific pattern of lymphocyte infiltration and cytokine secretion along the different phases of the acute EAE model in Lewis rat that differs from those already described in chronic or relapsing-remitting mouse models, where Th17-cells were found mostly during the peak, suggesting a specific role of these lymphocytes and cytokines in the evolution of this acute EAE model.

Building on the dramatic success of the global effort to eradicate rinderpest we now wish to draw attention to a related but significantly different morbillivirus disease, peste des petits ruminants (PPR), also known variously as goat plague, pseudorinderpest, pneumoenteritis and kata.

This paper reports a concatemeric RNA in a strain of epizootic haemorrhagic disease virus (EHDV) serotype 5. Sequencing showed that the concatemeric RNA contains two identical full-length copies of genome segment 9, arranged in series, which has apparently replaced the monomeric form of the segment. In vitro translation demonstrated that the concatemeric RNA can act as a viable template for VP6 translation, but that no double-sized protein is produced. Studies were also performed to assess whether mutations might be easily introduced into the second copy (which might indicate some potential evolutionary significance of a concatemeric RNA segment), however multiple (n = 40) passages generated no changes in the sequence of either the upstream or downstream segments. Further, we present results that demonstrate the presence of concatemers or partial gene duplications in multiple segments of different orbiviruses (in tissue culture and purified virus), suggesting their generation is likely to be a normal feature of orbivirus replication