Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.23 (beta-galactosidase)
 14,648 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The emergence of T cell-tropic, syncytium-inducing (T-tropic/SI) HIV-1 variants from the background of macrophage-tropic, non-syncytium-inducing (M-tropic/NSI) strains is associated with disease progression in infected individuals. HIV89.6 is a primary isolate with a transitional phenotype: like M-tropic strains it replicates in primary macrophages and lymphocytes but not in most transformed cells, yet it is also syncytium inducing. We have shown that HIV89.6 can utilize both the M-tropic and T-tropic cofactors CCR-5 and CXCR-4, respectively, in conjunction with CD4 for fusion and entry into otherwise nonpermissive nonhuman cells. To better understand the nature of restricted HIV89.6 infection of transformed cells, we analyzed its interaction with CD4-expressing transformed human HeLaCD4-LTR/beta-Gal cells, which contain the beta-galactosidase gene linked to the HIV-1 LTR. Here we show that HIV89.6 enters these cells and undergoes reverse transcription and integration. Furthermore, HIV89.6 induces LTR-driven beta-galactosidase expression, indicating Tat-dependent trans-activation, in a similar number of cells as the permissive T-tropic/SI isolate HIV(HXB). Acute infection with HIV89.6, however, produces markedly lower levels of p24 antigen and infectious virus per trans-activation-positive cell than HIV(HXB). In contrast, transfection results in high levels of expression for both viruses but HIV89.6 still fails to establish spreading infection. HIV89.6 is also blocked after entry in two other nonpermissive cell lines, SUP-T1 and U937. HIV89.6 arrest in HeLaCD4-LTR/beta-Gal cells at a stage subsequent to entry, reverse transcription, integration, and Tat expression is a novel level at which HIV-1 strain- and cell-specific restrictions define host cell tropism. These studies emphasize that complex patterns of tropism are determined by the interplay of permissive or restricted virus-cell interactions at multiple steps in the replication cycle.
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PMID:Abortive infection in HeLaCD4 cells by a primary HIV type 1 isolate: implications for differential host cell tropism. 917 Dec 20

Respiratory infection by Actinobacillus pleuropneumoniae causes a highly pathogenic necrotizing pleuropneumonia with severe edema, hemorrhage and fever. Acute infection is characterized by expression of inflammatory cytokines, including interleukin-1 (IL-1), IL-6 and IL-8. To determine if high level production of inflammatory cytokines contributed to disease pathogenesis, we investigated if inhibiting macrophage activation with adenovirus type 5-expressed IL-10 (Ad-5/IL-10) reduced the severity of acute disease. Porcine tracheal epithelial cells infected with Ad-5/IL-10 produced bioactive human IL-10. When pigs were intratracheally infected with A. pleuropneumoniae, pigs pretreated with Ad-5/IL-10 showed a significant reduction in the amount of lung damage when compared to adenovirus type 5-expressing beta-galactosidase (Ad-5/beta-Gal)-treated and untreated pigs. In addition, serum zinc levels were unchanged, the lung weight/body weight ratio (an indicator of vascular leakage) was significantly reduced, and lung pathology scores were reduced. Myeloperoxidase activity in lung lavage fluid samples, an indicator of neutrophil invasion, was decreased to levels similar to that seen in pigs not infected with A. pleuropneumoniae. Reduction in inflammatory cytokine levels in lung lavage fluid samples correlated with the clinical observations in that pigs pretreated with Ad-5/IL-10 showed a corresponding reduction of IL-1 and tumor necrosis factor (TNF) compared with untreated and Ad-5/beta-Gal-treated pigs. IL-6 levels were unaffected by pretreatment with Ad-5/IL-10, consistent with observations that IL-6 was not derived from alveolar macrophages. Since inflammatory cytokines are expressed at high levels in acute bacterial pleuropneumonia, these results indicate that macrophage activation, involving overproduction of IL-1 and TNF, is a prime factor in infection-related cases of massive lung injury.
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PMID:Interleukin-10 gene therapy-mediated amelioration of bacterial pneumonia. 1089 82