SUMMARY Cell‐mediated T‐helper type‐1 (Th1) responses play a vital role in the immunopathogenesis of genital infections caused by herpes simplex virus 2 (HSV‐2). We investigated the role of Th responses in HSV‐2 infection at different disease stages by analysing the production of Th cytokines in HSV‐stimulated peripheral blood mononuclear cells (PBMCs). IFN‐γ production decreased over time following a recurrence, whereas levels of IL‐10, and to a lesser extent IL‐2, remained elevated during this period. In addition, PBMCs from asymptomatic seropositive individuals produced high levels of IFN‐γ and low levels of IL‐10, in contrast to individuals with a history of genital ulcers. Following a recurrence, virus copy number in the genital lesions decreased progressively over time, in a manner similar to IFN‐γ production by HSV‐2‐stimulated PBMCs. Enhanced production of IFN‐γ may modulate HSV replication and B7 expression on monocytic cells of HSV‐infected individuals. In contrast to seronegative controls, IFN‐γ failed to enhance B7 expression on monocytic cells of HSV‐infected individuals. In addition, monocytic cells from HSV‐2‐infected individuals with recurrent disease supported greater HSV replication than did those of HSV‐infected asymptomatic individuals or seronegative controls. Furthermore, addition of IFN‐γ resulted in enhanced HSV replication in monocytic cells of HSV‐infected individuals with recurrent disease, in contrast to the inhibition observed in HSV‐seropositive asymptomatic individuals and seronegative controls. Taken together, our results suggest that dysregulated production of IFN‐γ at different disease stages and the impaired ability of monocytic cells to respond to IFN‐γ may play a role in the pathogenesis of recurrent genital herpes disease.

The genome of adenoviruses is a double-stranded linear DNA molecule with inverted terminal repeats about 100 base pairs (bp) in length and a terminal protein covalently linked to the 5' nucleotide of each strand. Both of these features permit the formation of DNA circles, the inverted repeats allowing the circularization of single-stranded DNA and the terminal protein the joining of one or more molecules to yield double-stranded circles or concatemers. However, although the existence of covalently closed circles has been postulated, double-stranded viral DNA purified from virions or infected cells by conventional methods (that is, using proteases and phenol or chloroform) has always been obtained in a linear form. Here, we present evidence for the existence in adenovirus 5 (Ad5) infected cells of novel structures resulting from covalent head-to-tail joining of viral DNA molecules and show that these structures are due at least in part to the formation of covalently closed circles.

P19 embryonal carcinoma (EC) cells are multipotential stem cells which can be induced to differentiate in vitro into a variety of cell types, including cardiac muscle cells. A cloned human cardiac actin (CH-actin) gene was transfected into P19 cells, and stable transformants were isolated. Low levels of CH-actin mRNA were present in transformed EC cells, but a marked increase in the level of CH-actin mRNA was found as these cells differentiated into cardiac muscle. The accumulation of CH-actin mRNA paralleled that of the endogenous mouse cardiac actin mRNA. A chimeric gene, which consisted of the CH-actin promoter linked to the herpes simplex virus thymidine kinase coding region, was constructed and transfected into P19 cells. In these transformants, the thymidine kinase protein was located almost exclusively in cardiac muscle cells and was generally not detectable in EC or other nonmuscle cells. These results suggest that the transfected CH-actin promoter functions in the appropriate developmental and tissue-specific manner during the differentiation of multipotential EC cells in culture.

: Two countries (Argentina and Uruguay) maintained continuous surveillance during the study period. Some countries gathered data periodically and several others were unable to initiate antimicrobial surveillance as a result of lack of resources. The percentage of penicillin-resistant N. gonorrhoeae isolated in the region over the decade varied considerably (1.0-11.9% carried chromosomal resistance and 17.9-38.8% produced beta-lactamase) with an overall trend to declining numbers of penicillin-resistant isolates. For tetracycline, 7.4% to 36.3% carried chromosomal resistance, whereas 12.0% to 27.4% carried plasmid-mediated resistance. There were no reports of ciprofloxacin-resistant isolates, although N. gonorrhoeae with decreased susceptibility to ciprofloxacin and azithromycin as well as spectinomycin-resistant isolates were identified in some countries.

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