Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.49 (reverse transcriptase)
 31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This chapter will describe methods that may be used to deliver agents to HIV-infected cells. These materials may be used for therapeutic or experimental purposes. There are several general approaches to delivering compounds to human immunodeficiency cells (HIV)-infected cells. All cells may be exposed to materials that only have an effect or become activated in HIV-infected cells. Examples include drugs that are specific for HIV-encoded enzymes, such as reverse transcriptase or protease, or genes that are expressed under the control of the HIV-LTR. Lack of specificity is a major limitation to this approach; for example, reverse transcriptase inhibitors also inhibit cellular DNA polymerases and cellular transcription factors clan initiate low-level-transcription off the HIV-LTR, even in the absence of tat. The alternative approach, which is the subject of this chapter, is to target the materials specifically to the infected cells. We have used monoclonal antibodies (MAbs) to deliver toxins to HIV-infected cells, but others have used this approach to deliver antiviral agents, liposomes, and even genes.
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PMID:11 Targeting HIV-Infected Cells. 2131 47

To silence a mammalian gene by RNAi using an encoded trigger, a short-hairpin RNA (shRNA) is integrated into the host cell genome as a stable transgene. Target cells are infected with viral plasmid containing shRNA inserted into the vector backbone. Before infection, the plasmid is transfected into a packaging cell line, which provides the trans-acting factors necessary for virus production. These include, minimally, capsid proteins and reverse transcriptase, but they can also include other regulatory factors (e.g., tat for some lentiviral vectors). It is critical to choose the correct packaging cell system for the viral backbone to be used. The packaging cell also defines the host range of the virus, depending on the envelope protein that it expresses. Ecotropic viruses are limited to rodent hosts, whereas amphotropic viruses have a broader host range that also includes humans. Often, investigators will express a nonretroviral envelope, such as vesicular stomatitus virus (VSV) glycoprotein, to enhance virus stability and host range and to enable viruses to be concentrated following production. Although viruses carrying shRNAs are packaged almost identically to viruses carrying protein-encoding genes, one twist is worth noting. shRNAs are efficiently cleaved by the host RNAi biogenesis machinery, which can reduce the level of viral genomic RNAs and consequently viral titers. Therefore, titers can be enhanced by cotransfecting the viral plasmid with a small interfering RNA (siRNA) that targets DGCR-8/Pasha, which is a core microRNA (miRNA) biogenesis component. siRNAs against Drosha can also be used.
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PMID:Packaging shRNA retroviruses. 2390 12

Quantitative humoral profiling of recent samples from a human immunodeficiency virus (HIV)-infected adult who was cured following a delta32/delta32 CCR5 stem cell transplant in 2007 revealed no antibodies against p24, matrix, nucleocapsid, integrase, protease, and gp120, but low levels of antibodies against reverse transcriptase, tat, and gp41. Antibody levels to these HIV proteins persisted at high and stable levels in most noncontrollers, elite controllers, and antiretroviral-treated subjects, but a rare subset of controllers had low levels of antibodies against matrix, reverse transcriptase, integrase, and/or protease. Comprehensive HIV antibody profiles may prove useful for monitoring curative interventions.
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PMID:HIV antibody characterization as a method to quantify reservoir size during curative interventions. 2428 82


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