Surgery for Jaccoud Arthropathy: A Systematic Review.

INTRODUCTION: Jaccoud arthropathy (JA) is characterized by the presence of joint deformities similar to those seen in rheumatoid arthritis but generally with a "reversible" pattern. The etiopathogenic mechanisms are not known, and its therapeutical approach has been regarded as disappointing. The aim of the present study was to perform a systematic review of the literature on the scientific evidence of the surgical procedures for JA. METHODS: The MEDLINE, LILACS, and Scielo databases were searched using the following keywords: "systemic lupus erythematosus," "rheumatic fever," "Jaccoud arthropathy," "deforming arthropathy," "surgery," and their corresponding terms in Portuguese and Spanish. The search period was between 1966 and 2014. RESULTS: Only 7 articles fulfilled the inclusion criteria, and a total of 58 patients underwent surgical procedures for JA. Such studies were limited to small case series, there was no uniform definition of the outcome, and the follow-up time varied largely. CONCLUSIONS: There is no consensus on the best approach for the surgical procedures in patients with JA, who are the best candidates to undergo this, and when to indicate the procedure.

Severe Jaccoud's arthropathy in systemic lupus erythematosus.

Jaccoud's arthropathy (JA) is a clinical situation nowadays present mostly in systemic lupus erythematosus (SLE). It is characterized by the presence of joint deformities such as "swan neck," ulnar deviation and "Z-thumb" resembling rheumatoid arthritis (RA) but that are passively correctable and without bone erosion on plain radiographs. From our cohort of SLE patients with JA, we selected a subgroup with a more severe form of this arthropathy and looked at their clinical and laboratory profile as well as studied the magnetic resonance imaging (MRI) findings or ultrasound (US) obtained from the hand with most evident deformities. Seven SLE patients with a severe form of JA were identified. All seven patients have "swan neck," ulnar deviation and "Z-thumb" deformities. Two out of seven had "mutilans-type JA" and four had fixed deformities in the metacarpophalangeal (MCP) joints. The MRI of the hand with more evident deformity clinically performed in six cases and US performed in one case showed mild synovitis in five and moderate synovitis in two patients, mild flexor tenosynovitis in six and severe tenosynovitis in one. Only two small bone erosions were observed in the second and third MCP joints of one patient with moderate synovitis. Severe JA compromises the functional capacity of the joints and imposes the risk of misdiagnosis of RA. With the improvement of the survival rate of SLE and the lack of specific prophylactic or therapeutical measures for JA, it is reasonable to assume that more and more cases of severe JA are going to be identified.

Viral fitness implications of variation within an immunodominant CD8+ T-cell epitope of HIV-1.

Cytotoxic T-lymphocyte (CTL) epitopes within the HIV genome are subject to negative and positive selective pressures, the balance of which influences CTL escape at a given epitope. We investigated whether viral fitness requirements dictate conservation of the HLA-A2 restricted immunodominant epitope SLYNTVATL (SL9). Viral clones incorporating changes throughout the SL9 epitope region were compared to consensus SL9 virus in terms of replication kinetics and relative viral fitness. Constructs recapitulating in vivo SL9-CTL escape variants showed markedly little effect on replication and fitness, as did non-natural conservative mutations targeting immunologically relevant positions of the epitope. Although certain residues of the epitope were constrained by viral requirements, our research reveals that there are multiple SL9 variants that are well tolerated virologically but fail to arise in vivo. In light of this data, assumptions regarding the balance of immune and viral selective pressures on this immunodominant epitope sequence need to be reassessed.

In vitro concatemer formation catalyzed by vaccinia virus DNA polymerase.

During poxvirus infection, both viral genomes and transfected DNAs are converted into high-molecular-weight concatemers by the replicative machinery. However, aside from the fact that concatemer formation coincides with viral replication, the mechanism and protein(s) catalyzing the reaction are unknown. Here we show that vaccinia virus DNA polymerase can catalyze single-stranded annealing reactions in vitro, converting linear duplex substrates into linear or circular concatemers, in a manner directed by sequences located at the DNA ends. The reaction required > or =12 bp of shared sequence and was stimulated by vaccinia single-stranded DNA-binding protein (gpI3L). Varying the structures at the cleaved ends of the molecules had no effect on efficiency. These duplex-joining reactions are dependent on nucleolytic processing of the molecules by the 3'-to-5' proofreading exonuclease, as judged by the fact that only a 5'-(32)P-end label is retained in the joint molecules and the reaction is inhibited by dNTPs. The resulting concatemers are joined only through noncovalent bonds, but can be processed into stable molecules in E. coli, if the homologies permit formation of circular molecules. This reaction provides a starting point for investigating the mechanism of viral concatemer formation and can be used to clone PCR-amplified DNA.

The complete genome sequence of shope (rabbit) fibroma virus.

We have determined the complete DNA sequence of the Leporipoxvirus Shope fibroma virus (SFV). The SFV genome spans 159.8 kb and encodes 165 putative genes of which 13 are duplicated in the 12.4-kb terminal inverted repeats. Although most SFV genes have homologs encoded by other Chordopoxvirinae, the SFV genome lacks a key gene required for the production of extracellular enveloped virus. SFV also encodes only the smaller ribonucleotide reductase subunit and has a limited nucleotide biosynthetic capacity. SFV preserves the Chordopoxvirinae gene order from S012L near the left end of the chromosome through to S142R (homologs of vaccinia F2L and B1R, respectively). The unique right end of SFV appears to be genetically unstable because when the sequence is compared with that of myxoma virus, five myxoma homologs have been deleted (C. Cameron, S. Hota-Mitchell, L. Chen, J. Barrett, J.-X. Cao, C. Macaulay, D. Willer, D. Evans, and G. McFadden, 1999, Virology 264, 298-318). Most other differences between these two Leporipoxviruses are located in the telomeres. Leporipoxviruses encode several genes not found in other poxviruses including four small hydrophobic proteins of unknown function (S023R, S119L, S125R, and S132L), an alpha 2, 3-sialyltransferase (S143R), a protein belonging to the Ig-like protein superfamily (S141R), and a protein resembling the DNA-binding domain of proteins belonging to the HIN-200 protein family S013L). SFV also encodes a type II DNA photolyase (S127L). Melanoplus sanguinipes entomopoxvirus encodes a similar protein, but SFV is the first mammalian virus potentially capable of photoreactivating ultraviolet DNA damage.

The complete DNA sequence of myxoma virus.

Myxomatosis in European rabbits is a severely debilitating disease characterized by profound systemic cellular immunosuppression and a high rate of mortality. The causative agent, myxoma virus, is a member of the poxvirus family and prototype of the Leporipoxvirus genus. As a major step toward defining the genetic strategies by which the virus circumvents host antiviral responses, the genomic DNA sequence of myxoma virus, strain Lausanne, was determined. A total of 171 open reading frames were assigned to cover the 161.8-kb genome, including two copies each of the 12 genes that map within the 11.5-kb terminal inverted repeats. Database searches revealed a central core of approximately 120 kb that encodes more than 100 genes that exhibit close relationships to the conserved genes of members of other poxvirus genera. Open reading frames with predicted signal sequences, localization motifs, or homology to known proteins with immunomodulatory or host-range functions were examined more extensively for predicted features such as hydrophobic regions, nucleic acid binding domains, ankyrin repeats, serpin signatures, lectin domains. and structural cysteine spacings. As a result, several novel, potentially immunomodulatory proteins have been identified, including a family with multiple ankyrin-repeat domains, an OX-2 like member of the neural cell adhesion molecule family, a third myxoma serpin, a putative chemokine receptor fragment, two natural killer receptor-like species, and a variety of species with domains closely related to diverse host immune regulatory proteins. Coupled with the genomic sequencing of the related leporipoxvirus Shope fibroma virus, this work affirms the existence of a conserved complement of poxvirus-specific core genes and expands the growing repertoire of virus genes that confer the unique capacity of each poxvirus family member to counter the immune responses of the infected host.

Vaccinia virus DNA polymerase promotes DNA pairing and strand-transfer reactions.

Vaccinia virus infection results in the synthesis of a protein that promotes joint molecule formation and strand-transfer reactions in vitro. We show here that this activity is also expressed by vaccinia DNA polymerase (gpE9L). Recombinant vaccinia polymerase was produced using a hybrid vaccinia/T7 expression system and purified to homogeneity. This protein catalyzed joint molecule formation and strand transfer in vitro in reactions containing single-stranded circular and linear duplex DNAs. The reaction required homologous substrates and magnesium ions and was stimulated by DNA aggregating agents such as spermidine HCl and Escherichia coli single-strand DNA binding protein. There was no requirement for a nucleoside triphosphate cofactor. The reaction ceased when approximately 20% of the double-stranded substrate had been incorporated into joint molecules and required stoichiometric quantities of DNA polymerase (0.5-1 molecules of polymerase per double-stranded DNA end). Electron microscopy showed that the joint molecules formed during these reactions contained displaced strands and thus represented the products of a strand-exchange reaction. We also reexamined the link between replication and recombination using a luciferase-based transfection assay and cells infected with DNA polymerase Cts42 mutant viruses. These data substantiate the claim that there exists an inextricable link between replication and recombination in poxvirus-infected cells. Together, these biochemical and genetic data suggest a way of linking poxviral DNA replication with genetic recombination.