An Induced Hypersensitive-Like Response Limits Expression of Foreign Peptides via a Recombinant TMV-Based Vector in a Susceptible Tobacco

BACKGROUND: By using tobacco mosaic virus (TMV)-based vectors, foreign epitopes of the VP1 protein from food-and-month disease virus (FMDV) could be fused near to the C-terminus of the TMV coat protein (CP) and expressed at high levels in susceptible tobacco plants. Previously, we have shown that the recombinant TMV vaccines displaying FMDV VP1 epitopes could generate protection in guinea pigs and swine against the FMDV challenge. Recently, some recombinant TMV, such as TMVFN20 that contains an epitope FN20 from the FMDV VP1, were found to induce local necrotic lesions (LNL) on the inoculated leaves of a susceptible tobacco, Nicotiana tabacum Samsun nn. This hypersensitive-like response (HLR) blocked amplification of recombinant TMVFN20 in tobacco and limited the utility of recombinant TMV vaccines against FMDV. METHODOLOGY/PRINCIPAL FINDINGS: Here we investigate the molecular mechanism of the HLR in the susceptible Samsun nn. Histochemical staining analyses show that these LNL are similar to those induced in a resistant tobacco Samsun NN inoculated with wild type (wt) TMV. The recombinant CP subunits are specifically related to the HLR. Interestingly, this HLR in Samsun nn (lacking the N/N'-gene) was able to be induced by the recombinant TMV at both 25°C and 33°C, whereas the hypersensitive response (HR) in the resistant tobacco plants induced by wt TMV through the N/N'-gene pathways only at a permissive temperature (below 30°C). Furthermore, we reported for the first time that some of defense response (DR)-related genes in tobacco were transcriptionally upregulated during HLR. CONCLUSIONS: Unlike HR, HLR is induced in the susceptible tobacco through N/N'-gene independent pathways. Induction of the HLR is associated with the expression of the recombinant CP subunits and upregulation of the DR-related genes

Plant virus particles carrying tumour antigen activate TLR7 and induce high levels of protective antibody

Induction of potent antibody is the goal of many vaccines targeted against infections or cancer. Modern vaccine designs that use virus-like particles (VLP) have shown efficacy for prophylactic vaccination against virus-associated cancer in the clinic. Here we used plant viral particles (PVP), which are structurally analogous to VLP, coupled to a weak idiotypic (Id) tumour antigen, as a conjugate vaccine to induce antibody against a murine B-cell malignancy. The Id-PVP vaccine incorporates a natural adjuvant, the viral ssRNA, which acts via TLR7. It induced potent protective anti-Id antibody responses in an in vivo mouse model, superior to the "gold standard" Id vaccine, with prevalence of the IgG2a isotype. Combination with alum further increased antibody levels and maintained the IgG2a bias. Engagement of TLR7 in vivo was followed by secretion of IFN-? by plasmacytoid dendritic cells and by activation of splenic CD11chi conventional dendritic cells. The latter was apparent from up-regulation of co-stimulatory molecules and from secretion of a wide range of inflammatory cytokines and chemokines including the Th1-governing cytokine IL-12, in keeping with the IgG2a antibody isotype distribution. PVP conjugates are a novel cancer vaccine design, offering an attractive molecular form, similar to VLP, and providing T-cell help. In contrast to VLP, they also incorporate a safe "in-built" ssRNA adjuvant

One word or two? Psycholinguistic and sociolinguistic interpretations of meaning in a court case

What relative weighting should be given to court case, to psycholinguistic and sociolinguistic explanations of an alleged offence? We review the case of an African-American plaintiff, who claimed that her receipt of work of a framed document with the title "Temporary Coon Ass Certificate" from a white mailer supervisory-level employee in the same agency constituted racial discrimination in the workplace. Dialect research conducted by JJS, as expert witness for the prosecution, demonstrated that the dialectical use of coon ass to refer to Cajuns (white settlers of French descent) was restricted to the states of Louisiana and south-eastern Texas. It was argued by the prosecution to be unreasonable to expect someone from another part of the USA to know the meaning of the word. The jury found in favour of the plaintiff. The prosecution case rested upon the premise that when a word is unknown, it will be interpreted by breaking it down into smaller units, in this case coon and ass, both derogatory terms, the former strongly racist. We explore the psycholinguistic rationale for this assumption and its converse, that when a word is well known to an individual (s)he may fail to see how it is constructed

One word or two? Psycholinguistic and sociolinguistic interpretations of meaning in a civil court case

What relative weighting should be given to court case, to psycholinguistic and sociolinguistic explanations of an alleged offence? We review the case of an African-American plaintiff, who claimed that her receipt of work of a framed document with the title "Temporary Coon Ass Certificate" from a white mailer supervisory-level employee in the same agency constituted racial discrimination in the workplace. Dialect research conducted by JJS, as expert witness for the prosecution, demonstrated that the dialectical use of coon ass to refer to Cajuns (white settlers of French descent) was restricted to the states of Louisiana and south-eastern Texas. It was argued by the prosecution to be unreasonable to expect someone from another part of the USA to know the meaning of the word. The jury found in favour of the plaintiff. The prosecution case rested upon the premise that when a word is unknown, it will be interpreted by breaking it down into smaller units, in this case coon and ass, both derogatory terms, the former strongly racist. We explore the psycholinguistic rationale for this assumption and its converse, that when a word is well known to an individual (s)he may fail to see how it is constructed