A SIGNIFICANT proportion (up to 70%) of individuals experience an acute clinical syndrome of varying severity associated with primary infection with the human immunodeficiency virus (HIV). We report here studies on six individuals who showed an acute HIV syndrome which generally resolved within four weeks, concomitant with a dramatic downregulation of viraemia. To characterize the T-cell-mediated primary immune response to HIV, we used combined semiquantitative polymerase chain reaction assay and cytofluorometry to analyse the T-cell antigen receptor repertoire in sequential peripheral blood mononuclear cells from the patients. We found major oligoclonal expansions in a restricted set of variable-domain beta-chain (V beta) families. Cells expressing the expanded V beta s predominantly expressed the CD8 T-cell differentiation antigen and mediated HIV-specific cytotoxicity. Major oligoclonal expansions of these CD8+ T lymphocytes may represent an important component of the primary immune response to viral infections and may help to clarify both the immunopathogenic and the protective mechanisms of HIV infection.

Class 1 integrons are widespread genetic elements that allow bacteria to capture and express gene cassettes that are usually promoterless. These integrons play a major role in the dissemination of antibiotic resistance among Gram-negative bacteria. They typically consist of a gene (intI) encoding an integrase (that catalyzes the gene cassette movement by site-specific recombination), a recombination site (attI1), and a promoter (Pc) responsible for the expression of inserted gene cassettes. The Pc promoter can occasionally be combined with a second promoter designated P2, and several Pc variants with different strengths have been described, although their relative distribution is not known. The Pc promoter in class 1 integrons is located within the intI1 coding sequence. The Pc polymorphism affects the amino acid sequence of IntI1 and the effect of this feature on the integrase recombination activity has not previously been investigated. We therefore conducted an extensive in silico study of class 1 integron sequences in order to assess the distribution of Pc variants. We also measured these promoters' strength by means of transcriptional reporter gene fusion experiments and estimated the excision and integration activities of the different IntI1 variants. We found that there are currently 13 Pc variants, leading to 10 IntI1 variants, that have a highly uneven distribution. There are five main Pc-P2 combinations, corresponding to five promoter strengths, and three main integrases displaying similar integration activity but very different excision efficiency. Promoter strength correlates with integrase excision activity: the weaker the promoter, the stronger the integrase. The tight relationship between the aptitude of class 1 integrons to recombine cassettes and express gene cassettes may be a key to understanding the short-term evolution of integrons. Dissemination of integron-driven drug resistance is therefore more complex than previously thought.

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Twenty Acinetobacter baumannii strains resistant to various antibiotics were analyzed for integron content and sequences of the amplification products. Sixteen clinical isolates had a class 1 integron, 2 contained an additional class 1 or class 2 integron, but no class 3 integron was detected. Thirteen strains had integrons with a single cassette: aac(3)-Ia (9 strains), ant(2؆)-Ia (2 strains), or aac(6)-Ib (2 strains); 1 had aac(6)-Ib and oxa20 cassettes and an unknown gene; and 1 had an integron containing ant(2؆)-Ia and an oxa3 cassette truncated by IS6100. The remaining strains harbored class 1 integrons with gene cassettes previously found in Enterobacteriaceae. One integron had a hybrid structure composed of intI2 and the 3 conserved segment of class 1 integrons. These data indicate that integrons play a major role in multidrug resistance in Acinetobacter.Integrons are genetic elements that can integrate, by sitespecific recombination, gene cassettes, usually antibiotic resistance genes (5). Three main classes of integrons have been described (22). All have a 5Ј conserved segment, including an intI gene encoding an integrase and an attI recombination site, but have distinct 3Ј conserved segments. In the class 1 integrons, the 3Ј conserved segment includes three open reading frames (ORFs)-qacE⌬1, a deletion derivative of the antiseptic resistance gene qacE; the sul1 sulfonamide resistance gene; and ORF5, of unknown function-or tni genes, as in Tn402 (18). The second class of integrons was found in transposon Tn7 and its derivatives, and its 3Ј conserved segment contains five tns genes involved in the movements of the transposon. A single class 3 integron has been reported to date, but its 3Ј conserved segment has not been characterized (2). Cassettes usually include a single ORF and, downstream, an attC site which is an imperfect inverted repeat sequence related to a 60-bp consensus sequence (4). The movements of cassettes are catalyzed by the integrase, which can excise or integrate cassettes by site-specific recombination between two specific sequences, either attI and attC or two attC sites. Cassette mobility results in the dissemination of resistance genes, and more than 50 cassettes have been described for gram-negative bacteria (5). This genetic flexibility allows numerous cassette rearrangements under antibiotic selective pressure, and study of these various assortments can lead to a better understanding of integron evolution. Acinetobacter, in particular Acinetobacter baumannii, is increasingly responsible for nosocomial infections in intensive care units and is often resistant to multiple antibiotics (27). Integrons have already been found in this species, but their cassette content has not been fully characterized (3, 25). The aim of our study was to search for the presence of the three classes of integrons in multidrug-resistant A. baumannii clinical isolates and to characterize their gene cassette assortments. MATERIALS AND METHODSBacterial strains. Twenty clinical A. baumannii strains isolated b...

Macrophages were infected with virulent B. abortus strain 2308 or attenuated strain 19. Intracellular bacteria were recovered at different times after infection and their proteomes compared. The virulent strain initially reduced most biosynthesis and altered its respiration, adaptations reversed later in infection. The attenuated strain was unable to match the magnitude of the virulent strain’s adjustments. The results provide insight into mechanisms utilized by Brucella to establish intracellular infections.

Down-regulation of the initial burst of viremia during primary HIV infection is thought to be mediated predominantly by HIV-specific cytotoxic T lymphocytes, and the appearance of this response is associated with major perturbations of the T cell receptor repertoire. Changes in the T cell receptor repertoire of virus-specific cytotoxic T lymphocytes were analyzed in patients with primary infection to understand the failure of the cellular immune response to control viral spread and replication. This analysis demonstrated that a significant number of HIV-specific T cell clones involved in the primary immune response rapidly disappeared. The disappearance was not the result of mutations in the virus epitopes recognized by these clones. Evidence is provided that phenomena such as high-dose tolerance or clonal exhaustion might be involved in the disappearance of these monoclonally expanded HIV-specific cytotoxic T cell clones. These findings should provide insights into how HIV, and possibly other viruses, elude the host immune response during primary infection.

The ultraviolet spectrograph instrument on the Juno mission (Juno-UVS) is a long-slit imaging spectrograph designed to observe and characterize Jupiter's far-ultraviolet (FUV) auroral emissions. These observations will be coordinated and correlated with those from Juno's other remote sensing instruments and used to place in situ measurements made by Juno's particles and fields instruments into a global context, relating the local data with events occurring in more distant regions of Jupiter's magnetosphere. Juno-UVS is based on a series of imaging FUV spectrographs currently in flight-the two Alice instruments on the Rosetta and New Horizons missions, and the Lyman Alpha Mapping Project on the Lunar Reconnaissance Orbiter mission. However, Juno-UVS has several important modifications, including (1) a scan mirror (for targeting specific auroral features), (2) extensive shielding (for mitigation of electronics and data quality degradation by energetic particles), and (3) a cross delay line microchannel plate detector (for both faster photon counting and David C. Slater deceased 30 May 2011.

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