No abstract

Apolipoprotein E (ApoE) belongs to a class of cellular proteins involved in lipid metabolism. ApoE is a polymorphic protein produced primarily in macrophages and astrocytes. Different isoforms of ApoE have been associated with susceptibility to various diseases including Alzheimer’s and cardiovascular diseases. ApoE expression has also been found to affect susceptibility to several viral diseases, including Hepatitis C and E, but its effect on the life cycle of HIV-1 remains obscure. In this study, we initially found that HIV-1 infection selectively up-regulated ApoE in human monocyte-derived macrophages (MDMs). Interestingly, ApoE knockdown in MDMs enhanced the production and infectivity of HIV-1, and was associated with increased localization of viral envelope (Env) proteins to the cell surface. Consistent with this, ApoE over-expression in 293T cells suppressed Env expression and viral infectivity, which was also observed with HIV-2 Env, but not with VSV-G Env. Mechanistic studies revealed that the C-terminal region of ApoE was required for its inhibitory effect on HIV-1 Env expression. Moreover, we found that ApoE and Env co-localized in the cells, and ApoE associated with gp160, the precursor form of Env, and that the suppression of Env expression by ApoE was cancelled by the treatment with lysosomal inhibitors. Overall, our study revealed that ApoE is an HIV-1-inducible inhibitor of viral production and infectivity in macrophages that exerts its anti-HIV-1 activity through association with gp160 Env via the C-terminal region, which results in subsequent degradation of gp160 Env in the lysosomes.

Long interspersed element-1 (LINE-1, L1) is a mobile genetic element comprising about 17% of the human genome. L1 utilizes an endonuclease to insert L1 cDNA into the target genomic DNA, which induces double-strand DNA breaks in the human genome and activates the DNA damage signaling pathway, resulting in the recruitment of DNA-repair proteins. This may facilitate or protect L1 integration into the human genome. Therefore, the host DNA repair machinery has pivotal roles in L1 mobility. In this study, we have, for the first time, demonstrated that the DNA repair protein, Rad18, restricts L1 mobility. Notably, overexpression of Rad18 strongly suppressed L1 retrotransposition as well as L1-mediated Alu retrotransposition. In contrast, L1 retrotransposition was enhanced in Rad18-deficient or knockdown cells. Furthermore, the Rad6 (E2 ubiquitin-conjugated enzyme)-binding domain, but not the Polη-binding domain, was required for the inhibition of L1 retrotransposition, suggesting that the E3 ubiquitin ligase activity of Rad18 is important in regulating L1 mobility. Accordingly, wild-type, but not the mutant Rad18-lacking Rad6-binding domain, bound with L1 ORF1p and sequestered with L1 ORF1p into the Rad18-nuclear foci. Altogether, Rad18 restricts L1 and Alu retrotransposition as a guardian of the human genome against endogenous retroelements.

The purpose of the present study is to examine the antibacterial and cytotoxic properties of methanol extract of leaves of Stephania japonica. The crude methanolic extract of S. japonica, n-hexane, chloroform and ethyl acetate soluble fractions of methanolic extract were screened for their antimicrobial activity against a wide range of both Gram-positive and Gram-negative bacteria by disc diffusion method. The crude extract showed moderate and n-Hexane, chloroform soluble fraction of crude extract showed mild antibacterial activity against both Gram-positive and Gram-negative bacteria. Ethyl acetate soluble fraction of the extract showed significant antimicrobial activity against Salmonella typhi, Escherichia coli and Bacillus cereus. The zones of inhibition produced by the crude methanolic extract, n-hexane, chloroform and ethyl acetate soluble fractions were found to be 12.80-16.55 mm, 12.60 mm, 5-14.30 mm and 10-20.25 mm, respectively, at a concentration of 30 g/disc. Chloroform, n-hexane and ethyl acetate soluble fractions of methanolic extract of S. japonica were screened for antitumor properties using brine shrimp lethality bioassay. A reputed cytotoxic agent vincristine sulphate was used as a positive control. From the results of the brine shrimp lethality bioassay, it can be well predicted that chloroform and ethyl acetate soluble fractions of methanolic extract of S. japonica possess cytotoxic principles (with LC50 66.488 mg/ml and LC50 45.662 mg/ml, respectively) comparison with positive control vincristine sulphate (with LC50 0.839 mg/ml). But n-hexane soluble fractions of methanolic extract of S. japonica exhibited no lethality effect on shrimp nauplii. DOI: http://dx.doi.org/10.3329/bjm.v28i2.11816 Bangladesh J Microbiol, Volume 28, Number 2, December 2011, pp 52-56

Vibrio alginolyticus has been thought to be a halophilic marine bacterium that causes diarrhea, otitis media and wound infection through the consumption of raw or inappropriately cooked sea food. It is one of the main Vibrio pathogens affecting marine animals, such as marine fish, shrimp and shellfish which lead to large economic damage. Although there are reports on the presence of this organism in the coastal area of other countries, not so much work has been done on the isolation and characterization of this species in Bangladesh. The present study was, therefore, undertaken to isolate and characterize V. alginolyticus organisms isolated from the rivers (fresh water) and estuaries (brackish water) of Bangladesh. A total of 9 isolates of Vibrio species were obtained from different water bodies (three from Meghna river, two from Shangu river and four from estuary) and provisionally identified as Vibrio alginolyticus following standard biochemical tests. All these 9 strains showed same pattern of antibiotic resistance to ampicillin, streotomycin, penicillin, but sensitive to nalidixic acid. In the virulence properties test, two isolates showed positive results for toxR gene and none of the isolates showed positive results for tdh gene. Challenge experiments in Singhi fish (Heteropneustes fossi) with the live cells and the culture filtrate prepared from the V. alginolyticus showed high mortality of the fish population. All these studies suggest the presence of pathogenic V. alginolyticus strains in the river water and estuarine bodies of Bangladesh and the extracellular toxin(s) of the V. alginolyticus might be one of the causes for fish mortality.