Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001486 (Adenovirus)
 3,125 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We recently demonstrated that the Adenovirus-5 E1A gene products (E1A), known E2F activators, can block the differentiation of murine preadipocytes and that differentiation suppression occurs at lower levels than required for full neoplastic transformation. Progressively higher levels were accompanied by apoptosis induction. To examine the role of the cellular Ras protooncogene product (Ras) in E1A function, E1A was expressed in C3H10T(1/2) (10T(1/2))-derived preadipocytes rendered deficient in Ras activity by transfection with inducible or constitutive antisense ras gene constructs (Ras-knockdowns). The results showed that, although even low amounts of E1A could block the differentiation of 10T(1/2) preadipocytes with normal Ras levels, even the highest E1A levels were unable to block the differentiation or induce transformation of Ras-knockdown preadipocytes. Ras downregulation did not affect E2F activation by E1A. Interestingly, our results further demonstrated a dramatic reduction in the levels of the E1A protein itself as differentiation progressed, with a concomitant reduction in E1A's ability to induce apoptosis as a result. These findings suggest for the first time that Ras, although cytoplasmic, is an integral component of the pathway whereby E1A, an oncoprotein believed to have primarily nuclear targets, suppresses differentiation or induces neoplastic conversion of murine preadipocytes.
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PMID:Adenovirus E1A requires c-Ras for full neoplastic transformation or suppression of differentiation of murine preadipocytes. 1729 29

T-cell based vaccines have been considered as attractive candidates for prevention of hepatitis C virus (HCV) infections. In this study we compared the magnitude and phenotypic characteristics of CD8+ T-cells induced by three commonly used viral vectors, Adenovirus-5 (Ad5), Vaccinia virus (VV) and Modified Vaccinia Ankara (MVA) expressing the HCV NS3/4A protein. C57/BL6 mice were primed with DNA expressing NS3/4A and boosted with each of the viral vectors in individual groups of mice. We then tracked the vaccine-induced CD8+ T-cell responses using pentamer binding and cytokine production analysis. Overall, our data indicate that the memory cells induced by Ad5 were inferior to those induced by VV or MVA. We found that Ad5 boosting resulted in rapid expansion and significantly higher frequencies of NS3-specific T-cells compared to VV and MVA boosting. However, the functional profiles, assessed through analysis of the memory cell marker CD127 and the anti-apoptotic molecule Bcl-2 in the blood, spleen, and liver; and measurements of interferon-gamma, tumor necrosis factor-alpha, and interleukin-2 production indicated significantly lower frequencies of long-lived memory T-cells following Ad5 boosting compared to VV and MVA. This same set of analyses suggested that the memory cells induced following boosting with MVA were superior to those induced by both Ad5 and VV. This superiority of the MVA-induced CD8+ T-cells was confirmed following surrogate challenge of mice with a recombinant mouse herpes virus expressing the HCV NS3 protein. Higher levels of NS3-specific CD8+ T-cells displaying the functional markers CD69, Ki67 and Granzyme B were found in the spleens of mice boosted with MVA compared to VV and Ad5, both alone and in combination. These data suggest that MVA may be a more successful viral vector for induction of effective CD8+ T-cell responses against hepatitis C virus.
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PMID:Qualitative differences in cellular immunogenicity elicited by hepatitis C virus T-Cell vaccines employing prime-boost regimens. 2873 46


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