An unusual case of vaccine-associated paralytic poliomyelitis.

The present article reports a case involving an immunocompetent, previously well child who, despite two previous doses of inactivated poliovirus vaccine, developed severe flaccid paralysis consistent with polio after receiving oral polio vaccine.

Le présent article rend compte du cas d'un enfant immunocompétent auparavant en santé qui, malgré deux doses antérieures de vaccin inactivé contre le poliovirus, a contracté une grave paralysie flasque qui cadrait avec la polio après s'être fait administrer le vaccin antipolio-myélitique oral.

Phylogenetic analysis of viroid and viroid-like satellite RNAs from plants: a reassessment.

The proposed monophyletic origin of a group of subviral plant pathogens (viroids and viroid-like satellite RNAs), as well as the phylogenetic relationships and the resulting taxonomy of these entities, has been recently questioned. The criticism comes from the (apparent) lack of sequence similarity among these RNAs necessary to reliably infer a phylogeny. Here we show that, despite their low overall sequence similarity, a sequence alignment manually adjusted to take into account all the local similarities and the insertions/deletions and duplications/rearrangements described in the literature for viroids and viroid-like satellite RNA, along with the use of an appropriate estimator of genetic distances, constitutes a data set suitable for a phylogenetic reconstruction. When the likelihood-mapping method was applied to this data set, the tree-likeness obtained was higher than that corresponding to a sequence alignment that does not take into consideration the local similarities. In addition, bootstrap analysis also supports the major groups previously proposed and the reconstruction is consistent with the biological properties of this RNAs.

Reconstruction of major column defects and pelvic discontinuity in revision total hip arthroplasty.

Acetabular reconstruction with severe bone loss after failed total hip arthroplasty is a difficult problem. Defects were defined as major segmental and cavitary loss (type III anterior or posterior) or pelvic discontinuity (type IV). Seventeen cases were treated, of which 7 were type III and 10 were type IV. Bulk allograft was used in 16 of 17 cases, of which 7 were whole acetabular grafts, 2 were posterior segmental acetabular grafts, and 7 were femoral heads. Fourteen of 17 patients were female. The extensile triradiate approach was used in 12 cases. Long pelvic bone plates were applied to the posterior column and anterior brim of the pelvis in most cases. Allografts united to host-bone in 15 cases. Average follow-up was 83 months. The overall revision rate was 47%, of which 3 of 7 press-fit and 2 of 10 cemented cups had failed. The dislocation rate for the extensile approach was 50%; 2 patients had excisional arthroplasty for infection, and 2 patients had exploration of the sciatic nerve for release from migrating pelvic plate screws. Because of the overall poor results, this approach cannot be recommended for general use.

Viroids and the nature of viroid diseases.

In its methodology, the unexpected discovery of the viroid in 1971 resembles that of the virus by Beijerinck some 70 years earlier. In either case, a novel type of plant pathogen was recognized by its ability to penetrate through a medium with pores small enough to exclude even the smallest previously known pathogen: bacteria as compared with the tobacco mosaic agent; viruses as compared with the potato spindle tuber agent. Interestingly, one of the two methods used by Beijerinck, diffusion of the tobacco mosaic agent into agar gels, is conceptually similar to one method used to establish the size of the potato spindle tuber agent, namely polyacrylamide gel electrophoresis. Further work demonstrated that neither agent is an unusually small conventional pathogen (a microbe in the case of the tobacco mosaic agent; a virus in the case of the potato spindle tuber agent), but that either agent represents the prototype of a fundamentally distinct class of pathogen, the viruses and the viroids, respectively. With the viroids, this distinction became evident once their unique molecular structure, lack of mRNA activity, and autonomous replication had become elucidated. Functionally, viroids rely to a far greater extent than viruses on their host's biosynthetic systems: Whereas translation of viral genetic information is essential for virus replication, viroids are totally dependent on their hosts' transcriptional system and, in contrast to viruses, no viroid-coded proteins are involved. Because of the viroids' simplicity and extremely small size they approach more closely even than viruses Beijerinck's concept of a contagium vivum fluidum.

Mexican papita viroid: putative ancestor of crop viroids.

The potato spindle tuber disease was first observed early in the 20th century in the northeastern United States and shown, in 1971, to be incited by a viroid, potato spindle tuber viroid (PSTVd). No wild-plant PSTVd reservoirs have been identified; thus, the initial source of PSTVd infecting potatoes has remained a mystery. Several variants of a novel viroid, designated Mexican papita viroid (MPVd), have now been isolated from Solanum cardiophyllum Lindl. (papita güera, cimantli) plants growing wild in the Mexican state of Aguascalientes. MPVd's nucleotide sequence is most closely related to those of the tomato planta macho viroid (TPMVd) and PSTVd. From TPMVd, MPVd may be distinguished on the basis of biological properties, such as replication and symptom formation in certain differential hosts. Phylogenetic and ecological data indicate that MPVd and certain viroids now affecting crop plants, such as TPMVd, PSTVd, and possibly others, have a common ancestor. We hypothesize that commercial potatoes grown in the United States have become viroid-infected by chance transfer of MPVd or a similar viroid from endemically infected wild solanaceous plants imported from Mexico as germplasm, conceivably from plants known to have been introduced from Mexico to the United States late in the 19th century in efforts to identify genetic resistance to the potato late blight fungus, Phytophthora infestans.

Origin and evolution of viroids and viroid-like satellite RNAs.

Viroids, the smallest and simplest agents of infectious disease, cause a number of economically important diseases of crop plants. Present evidence indicates that most of these diseases originated recently (in the 20th century) by chance transfer of viroids from endemically infected wild plants or by use of viroid-infected germplasm during plant breeding. Modern agricultural practices, such as widespread monoculture of genetically identical plants, and worldwide distribution of planting material, has made it possible for the pathogens to maintain themselves in the crop plants and to conquer new territories. Phylogenetic analysis of their nucleotide sequences indicates that viroids and satellite RNAs represent a monophyletic group, with all but the two self-cleaving viroids forming one cluster and the satellite RNAs another. The two self-cleaving viroids are phylogenetically distant from either cluster; they may represent ancestral forms. Results from site-directed mutagenesis experiments indicate that, upon exposure to selective pressures, viroids can evolve extremely rapidly, with another, fitter, component of the quasi-species often becoming dominant within days or weeks. This extreme plasticity of their nucleotide sequences establishes viroids as the most rapidly evolving biological system known.

The viroid: big punch in a small package.

Although viroids consist solely of short lengths of unencapsidated single-stranded circular RNA, they replicate autonomously in plants and cause diseases that are as varied and often as severe as those caused by plant viruses. All this, without ever serving as mRNAs. However, aside from some fascinating glimpses, the mechanisms of viroid pathogenesis remain largely enigmatic.

Viroids: the smallest and simplest agents of infectious disease. How do they make plants sick?

Viroids are autonomously replicating pathogens of higher plants that consist solely of unencapsidated, single-stranded, circular RNAs of 246-375 nucleotides. Despite their extreme simplicity, viroids cause syndromes in plants that are about as varied as those caused by plant viruses. Because viroids are not translated, their effects on plants must be a consequence of direct interaction of the viroid with host constituents. Although the molecular mechanisms of viroid pathogenesis are still unknown, analysis of molecular chimeras between viroids of different pathogenicity levels has revealed that the severity of symptoms is the result of complex interactions among three of the five viroid domains. In vitro experiments with purified mammalian protein kinase P68 have shown that the enzyme is strongly activated (phosphorylated) by viroid strains that incite moderate to severe symptoms, but far less by a mild strain. Activation of a plant homolog of P68 may be the triggering event in viroid pathogenesis.

Mechanism of viroid pathogenesis: differential activation of the interferon-induced, double-stranded RNA-activated, M(r) 68,000 protein kinase by viroid strains of varying pathogenicity.

Purified potato spindle tuber viroid (PSTVd) was added to an in vitro assay system containing purified interferon-induced, dsRNA-activated protein kinase (P68). Viroid RNA activated (phosphorylated) the enzyme, although with less efficiency than did the synthetic, perfectly matched poly I-poly C. In binding experiments, RNA transcripts of the intermediate strain of PSTVd were shown to specifically bind to a P68-antibody complex. Activation of the enzyme by a strain of PSTVd that results in severe symptoms in infected tomato plants was at least ten-fold that by the mild strain. Activation by a strain that results in intermediate symptoms was quantitatively similar to activation by the severe strain. To our knowledge, this is the first demonstration of a differential effect of viroid strains inducing different levels of pathology on any biochemical or metabolic system investigated. This differential effect suggests that activation of a plant enzyme homologous to mammalian P68 protein kinase may represent the triggering event in viroid pathogenesis. Differential activation of P68 is surprising, because the primary structures of the mild and severe PSTVd strains analyzed differ by only a two-nucleotide inversion (UUC-->CUU) in the lower portion of the 'pathogenicity' region of the molecules. This change, according to thermodynamic calculations, should have only a minor effect on the secondary structure of the viroid molecule. Binding assays indicated that PSTVd specifically binds to P68.

Identification of multiple structural domains regulating viroid pathogenicity.

To investigate the role of individual structural domains in viroid pathogenicity and replication, a series of interspecific chimeras was constructed by exchanging the terminal left (TL) and/or pathogenicity (P) domains between tomato apical stunt (TASVd) and citrus exocortis (CEVd) viroids. All six chimeras tested were replicated stably in tomato, and the symptoms exhibited by infected plants were intermediate between those induced by the parental viroids. Quantitative comparisons of symptom development and progeny accumulation revealed that: (i) the TL domain of TASVd contains a determinant required for appearance of severe veinal necrosis in tomato, (ii) the severe epinasty and stunting characteristic of TASVd requires the presence of its TL and P domains, and (iii) the variable (V) and terminal right (TR) domains comprising the right side of the native structure also play an important role in viroid pathogenicity. Chimeras containing the right side of TASVd accumulated to higher levels early in infection, and infected plants developed more severe symptoms than those whose right halves were derived from CEVd. Although the individual contributions of the TL and P domains to symptom induction could not be completely separated from that of viroid titer, the TL domain appears to exert a greater effect upon symptom severity than does the P domain. The TL, P, V, and TR domains of TASVd and CEVd contain three discrete regions of sequence and/or structural variability that may correspond to the pathogenicity determinants uncovered by our genetic analysis.

Subviral pathogens of plants: viroids and viroidlike satellite RNAs.

Contrary to earlier beliefs, viruses are not the smallest causative agents of infectious diseases. Single-stranded RNAs as small as 246 nucleotides exist in certain higher plants and cause more than a dozen crop diseases. These RNAs have been termed viroids. Despite their extremely limited information content, viroids replicate autonomously in susceptible cells--that is, they do not require helper functions from simultaneously replicating conventional viruses. Viroids are covalently closed circular molecules with a characteristic rodlike secondary structure in which short helical regions are interrupted by internal and bulge loops. Viroids are not translated; they are replicated by a host enzyme (or enzymes) (probably RNA polymerase II) via oligomeric RNA intermediates by a rolling circle mechanism. Viroidlike satellite RNAs resemble viroids in size and molecular structure, but are found within the capsids of specific helper viruses on which they depend for their own replication. These RNAs are of great interest to molecular biology for at least two reasons: 1) they are the smallest and simplest replicating molecules known, and 2) they may represent living fossils of precellular evolution in a hypothetical RNA world.

Indian bunchy top disease of tomato plants is caused by a distinct strain of citrus exocortis viroid.

A viroid has been isolated from tomato plants affected by Indian bunchy top disease of tomato (Lycopersicon esculentum Mill.). In dot blot hybridization assays with 32P-labelled cRNA probes specific for the detection of various viroids, the Indian viroid was shown to be most closely related to the citrus exocortis viroid (CEVd). Sequence determination showed that the viroid consists of 372 nucleotides and confirmed its close relationship with CEVd. The viroid, for which we propose the acronym CEVd-t, differs from the Australian CEVd strains A and B by 36 and 47 nucleotides, respectively, and from the Spanish grapevine isolate by 52 changes. A phylogenetic analysis confirmed the closet relationship with CEVd in all structural domains, except the pathogenicity and left-terminal domains, which are closely related to the corresponding domains of the potato spindle tuber and tomato apical stunt viroids, respectively.

Phylogeny of viroids, viroidlike satellite RNAs, and the viroidlike domain of hepatitis delta virus RNA.

We report a phylogenetic study of viroids, some plant satellite RNAs, and the viroidlike domain of human hepatitis delta virus RNA. Our results support a monophyletic origin of these RNAs and are consistent with the hypothesis that they may be "living fossils" of a precellular RNA world. Moreover, the viroidlike domain of human hepatitis delta virus RNA appears closely related to the viroidlike satellite RNAs of plants, with which it shares some structural and functional properties. On the basis of our phylogenetic analysis, we propose a taxonomic classification of these RNAs.