The bovine leukemia virus encapsidation signal is composed of RNA secondary structures.

The encapsidation signal of bovine leukemia virus (BLV) was previously shown by deletion analysis to be discontinuous and to extend into the 5' end of the gag gene (L. Mansky et al., J. Virol. 69:3282-3289, 1995). The global minimum-energy optimal folding for the entire BLV RNA, including the previously mapped primary and secondary encapsidation signal regions, was analyzed. Two stable stem-loop structures (located just downstream of the gag start codon) were predicted within the primary signal region, and one stable stem-loop structure (in the gag gene) was predicted in the secondary signal region. Based on these predicted structures, we introduced a series of mutations into the primary and secondary encapsidation signals in order to explore the sequence and structural information contained within these regions. The replication efficiency and levels of cytoplasmic and virion RNA were analyzed for these mutants. Mutations that disrupted either or both of the predicted stem-loop structures of the primary signal reduced the replication efficiency by factors of 7 and 40, respectively; similar reductions in RNA encapsidation efficiency were observed. The mutant with both stem-loop structures disrupted had a phenotype similar to that of a mutant containing a deletion of the entire primary signal region. Mutations that disrupted the predicted stem-loop structure of the secondary signal led to similar reductions (factors of 4 to 6) in both the replication and RNA encapsidation efficiencies. The introduction of compensatory mutations into mutants from both the primary and secondary signal regions, which restored the predicted stem-loop structures, led to levels of replication and RNA encapsidation comparable to those of virus containing the wild-type encapsidation signal. Replacement of the BLV RNA region containing the primary and secondary encapsidation signals with a similar region from human T-cell leukemia virus (HTLV) type 1 or type 2 led to virus replication at three-quarters or one-fifth of the level of the parental virus, respectively. The results from both the compensatory mutants and BLV-HTLV chimeras indicate that the encapsidation sequences are recognized largely by their secondary or tertiary structures.

Helicobacter pylori: beyond peptic ulcer disease.

Beyond peptic ulcer disease, Helicobacter pylori infection is associated with intestinal-type gastric cancer and low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma. It is also currently implicated as a possible cause of dyspepsia and extraintestinal disorders such as coronary artery disease, rosacea, chronic urticaria, and delayed growth in children. There are strong epidemiological data from large cohort studies linking H. pylori to gastric adenocarcinoma. Several cofactors, including early childhood acquisition of infection, strain-specific differences, genetic predisposition of the host, and the environment, appear to play a role in the progression of chronic gastritis to gastric cancer. H. pylori infection is seen in over 90% of MALT lymphomas, and about 70% of localized nonbulky tumors will undergo complete histological regression after eradication of the bacterium. Because follow-up data are limited to less than 2 years, those undergoing H. pylori eradication as primary therapy for MALT lymphoma require frequent histological surveillance for tumor recurrence. There are conflicting data from short-term studies regarding the effect of H. pylori eradication on dyspeptic symptoms. The decision to test or not for H. pylori in the dyspeptic patient may become easier when well-controlled studies with longer periods of follow-up become available. Because H. pylori induces a systemic inflammatory response, investigators are beginning to explore possible extraintestinal disease associations with the infection. The global prevalence of both peptic ulcer disease and gastric cancer has led to studies focusing on noninvasive screening for H. pylori in high-risk populations and prevention of primary infection by means of vaccination.

Beta-lactams versus glycopeptides in treatment of subcutaneous abscesses infected with Staphylococcus aureus.

The antibacterial efficacies of the beta-lactam antibiotics nafcillin and cefazolin were compared with those of the glycopeptide antibiotics vancomycin and teicoplanin in rats with subcutaneous abscesses infected with methicillin-susceptible Staphylococcus aureus. Animals were treated with antibiotics or diluent for 3 or 7 days. Rats receiving any antibiotic treatment, with the exception of teicoplanin-treated animals at day 7, had lower bacterial counts in their abscesses than did controls at days 3 and 7. Rats in the nafcillin and cefazolin treatment groups had lower bacterial counts in their abscesses than did rats in the vancomycin and teicoplanin treatment groups at days 3 and 7. The beta-lactam antibiotics were more effective therapy than the glycopeptide antibiotics in rats with subcutaneous abscesses infected with methicillin-susceptible S. aureus. In vitro, animal, and clinical data comparing beta-lactam and glycopeptide treatment of S. aureus infections were reviewed along with the resulting treatment recommendations.