Recently it has been recognized that bacteriophages, the natural predators of bacteria can be used efficiently in modern biotechnology. They have been proposed as alternatives to antibiotics for many antibiotic resistant bacterial strains. Phages can be used as biocontrol agents in agriculture and petroleum industry. Moreover phages are used as vehicles for vaccines both DNA and protein, for the detection of pathogenic bacterial strain, as display system for many proteins and antibodies. Bacteriophages are diverse group of viruses which are easily manipulated and therefore they have potential uses in biotechnology, research, and therapeutics. The aim of this review article is to enable the wide range of researchers, scientists, and biotechnologist who are putting phages into practice, to accelerate the progress and development in the field of biotechnology.

In Pakistan more than 10 million people are living with Hepatitis C virus (HCV), with high morbidity and mortality. This article reviews the prevalence, genotypes and factors associated with HCV infection in the Pakistani population. A literature search was performed by using the keywords; HCV prevalence, genotypes and risk factors in a Pakistani population, in Pubmed, PakMediNet and Google scholar. Ninetyone different studies dating from 1994 to May 2009 were included in this study, and weighted mean and standard error of each population group was calculated. Percentage prevalence of HCV was 4.95% ± 0.53% in the general adult population, 1.72% ± 0.24% in the pediatric population and 3.64% ± 0.31% in a young population applying for recruitment, whereas a very high 57% ± 17.7% prevalence was observed in injecting drug users and 48.67% ± 1.75% in a multitransfused population. Most prevalent genotype of HCV was 3a. HCV prevalence was moderate in the general population but very high in injecting drug users and multi-transfused populations. This data suggests that the major contributing factors towards increased HCV prevalence include unchecked blood transfusions and reuse of injection syringes. Awareness programs are required to decrease the future burden of HCV in the Pakistani population.

Chronic infection with hepatitis C virus (HCV) can induce insulin resistance (IR) in a genotype-dependent fashion, thus contributing to steatosis, progression of fibrosis and resistance to interferon therapy. The molecular mechanisms in genotype 1 patients that lead to metabolic syndrome are still ambiguous. Based on our current understanding, HCV proteins associate with mitochondria and endoplasmic reticulum and promote oxidative stress. The latter mediates signals involving the p38 mitogen-activated protein kinase and activates nuclear factor kappa B. This transcription factor plays a key role in the expression of cytokines, tumor necrosis factor alpha (TNF-␣), interleukin 6, interleukin 8, tumor growth factor beta, and Fas ligand. TNF-␣ inhibits the function of insulin receptor substrates and decreases the expression of the glucose transporter and lipoprotein lipase in peripheral tissues, which is responsible for the promotion of insulin resistance. Furthermore, reduced adiponectin levels, loss of adiponectin receptors, and decreased anti-inflammatory peroxisome proliferator-activated receptor alpha in the liver of HCV patients may contribute to reduced fatty acid oxidation, inflammation, and eventually lipotoxicity. This chain of events may be initiated by HCV-associated IR and provides a direction for future research in the areas of therapeutic intervention. (HEPATOLOGY 2008;47:2127-2133

Several viral transcriptional activators have been shown to interact with the basal transcription factor TATA-binding protein (TBP). These associations have been implicated in facilitating the assembly of the transcriptional preinitiation complex. We report here that the hepatitis B virus protein X (pX) specifically binds to TBP in vitro. While truncations of the highly conserved carboxyl terminus of TBP abolished this binding, amino-terminal deletions had no effect. Deletion Infection by human hepatitis B virus (HBV) represents a major health problem. It is estimated that over 250 million people are chronically infected worldwide. Chronic infection has been associated with hepatocellular carcinoma (1). The HBV genome encodes four genes whose transcriptional activity is controlled by at least four promoters and two enhancer elements designated I and II. The 16.5-kDa protein X (pX), encoded by the X gene, can activate gene expression from diverse viral and cellular transcriptional control elements (2-7). pX does not interact directly with cis-acting DNA elements. The biochemical mechanism responsible for pX activity in the viral life cycle remains obscure. While little is known regarding the potential interactions between pX and cellular proteins, it is clear from numerous studies that pX may function by a number of distinct mechanisms (7). We have previously shown that pX mediates transcriptional transactivation by engaging in protein-protein interactions (8). pX was shown to enhance the DNA-binding specificity of the transcription factors ATF-2 and CREB. This interaction within the HBV enhancer element I leads to transactivation through the cAMP response element (8). Several cellular genes, including interleukin 8, intercellular adhesion molecule 1, c-myc, and major histocompatibility complex class I and class II genes, have been shown to be activated by pX via distinct transcription factors (9-13). Consistent with these findings, an NF-KB sequence located in the human immunodeficiency virus long terminal repeat was shown to be the target sequence of pX transactivation (5, 6). However, there is no direct evidence for a direct interaction between pX and these factors. pX has also been shown to increase an endogenous protein kinase C activity via signal transduction pathways (14,15). A recent report demonstrated interactions of pX with the p53 tumorsuppressor gene, and it was proposed that this interaction may impede DNA repair of host genes (16). The mechanism(s) by which pX is able to activate gene expression through a variety of promoters/enhancers has been the subject of intense investigation. Of interest is the observation that the general transcriptional factor TFIID [or the TATA-binding protein (TBP)] is the target of transactivation by a large number of viral and cellular factors. These include adenovirus ElA (17), herpes simplex virus 1 VP16 (18), Epstein-Barr virus Zta (19), human cytomegalovirus IE2 (20), human T-cell lymphotropic virus 1 Tax (21), and human immunodeficiency virus Tat (22). I...

The 78-kDa glucose-regulated protein (GRP78) is a major endoplasmic reticulum (ER) protein that can form stable associations with a variety of proteins retained in the ER because of underglycosylation or other conformational changes. In this study, we provide evidence at the transcriptional level that a conformationally abnormal protein, an altered herpes simplex virus type 1 envelope protein that is retained in the ER of a mammalian cell line, transactivates the grp78 promoter. In contrast, the normal viral envelope glycoprotein does not elevate grp78 promoter activity. Using a series of 5' deletions, linker-scanning, and internal deletion mutations spanning a 100-bp region from -179 to -80, we correlate the cis-acting regulatory elements mediating the activation of grp78 by malfolded proteins, glycosylation block, and the calcium ionophore A23187. We show that they all act through the same control elements, suggesting that they share a common signal. We report here that the highly conserved grp element, while important for basal level and induced grp78 expression, is functionally redundant. The single most important element, by linker-scanning analysis, is a 10-bp region that contains a CCAAT motif. It alone is not sufficient for promoter activity, but a 40-bp region (-129 to -90) that contains this motif is essential for mediating basal level and stress inducibility of the grp78 promoter. We show that the transcription factor CTF/NF-I is able to transactivate the grp78 promoter through interaction with this CCAAT motif.