HIV insertional cis-activation of the protooncogene c-fes in AIDS associated lymphomagenesis

Mack, Karl D.; Wci, R; Hcrndicr, B; Shiramizu, Bruce; Hurt, Mark H.; Abbey, Nancy W.; Cascon, R.; Elbaggari, Ahmed; McGrath, Michael S.

doi:10.1097/00042560-199704010-00155

Cited by 6 publications

(2 citation statements)

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“…An increased risk for cancer development risk in HIVseropositive individuals has also been observed and includes Kaposi sarcoma associated with HHV-8 infection [reviewed in 19] and Burkitt lymphoma associated with EBV infection [reviewed in 20], both resulting from reactivation of these adventitious viruses in patients with immunodeficiency, and in extremely rare cases, HIV-1 associated T-Cell lymphomas. In the latter case HIV-1 has been shown to be clonally integrated in the CD4+ T cell genome just upstream from the c-fes oncogene where the integrated HIV-LTR acted as an enhancer element for c-fes, leading to upregulated Fes expression [21][22][23].…”

Section: Potential Adverse Effects Attribu-table To Lentiviral Vectorsmentioning

confidence: 99%

State-of-the-Art Lentiviral Vectors for Research Use: Risk Assessment and Biosafety Recommendations

Pauwels¹,

Gijsbers²,

Toelen³

et al. 2009

CGT

108

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Lentiviral vectors (LV) are competent gene transfer vehicles, as used for both research and gene therapy applications, because of their stable integration in non-dividing and dividing cells and long-term transgene expression. Along with our understanding that LV offer solutions for gene therapy, biosafety concerns have uncovered risks due to insertional mutagenesis, the generation of replication competent lentiviruses (RCL) and vector mobilization. Researchers therefore continue to devote significant efforts in designing LV with improved efficacy and biosafety features.The choice of a particular LV system for experimental studies is often driven by functional considerations, including increased productivity and/or transduction efficiency. The design of safer vectors has also directly benefited researchers allowing them to conduct experimental studies with lower risk. Currently, vectors combine improved safety features (that decrease the risk of recombination and vector mobilization) with increased transduction efficiency. Hence, risks associated with the inadvertent transduction of cells of the investigator gain greater importance in assessing the overall risk of these vectors and become an important biosafety concern.This review outlines the different strategies used to improve LV biosafety by comparing state-of-the-art and emerging LV production systems and highlighting biosafety issues that can arise during their contained use. The few existing national and international biosafety recommendations that specifically address the use of LV in research are discussed and recommendations for most common research activities using LV are proposed.

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Section: Potential Adverse Effects Attribu-table To Lentiviral Vectorsmentioning

confidence: 99%

State-of-the-Art Lentiviral Vectors for Research Use: Risk Assessment and Biosafety Recommendations

Pauwels¹,

Gijsbers²,

Toelen³

et al. 2009

CGT

108

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show abstract

“…7,8 In humans, HIV integration may be responsible for some lymphomas. [9][10][11][12] Insertional mutagenesis and oncogenesis Lentiviruses typically insert into host DNA as a single non-rearranged copy. It is unknown how many integration events yield the desired level of transgene expression.…”

Section: Previous Experiences With Retroviral Vectorsmentioning

confidence: 99%