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The Immunological System and Neoplasia
Published in Julius P. Kreier, Infection, Resistance, and Immunity, 2022
The basic structure and the genomic map of retroviruses are depicted in Figure 12.1. Purified viruses contain a limited number of viral proteins. Two glycoproteins are expressed on the cell surface and are important for the attachment of the virus to the cells: a transmembrane protein or spike protein to which the second glycoprotein or “knob” is attached. These proteins are identified as glycoprotein (gp) 15 and gp 70, respectively in feline leukemia virus (FeLV), the number indica ting the molecular mass in kilodaltons. In addition, the virion contains the reverse transcriptase and four structural proteins: p27 (capsid protein), p15 (matrix protein), p10 (nucieocapsid protein), and p12 (inner coat protein). After virus enters the cells, the RNA is reverse transcribed into DNA, which is incorporated into the cellular genome. The incorporated DNA will persist in these cells. This group of retroviruses does not transform cells in vitro and tumors develop only after a prolonged incubation time in hosts. Some retroviruses, however, transform cells easily in vitro, and tumors develop rapidly in vivo. These acutely transforming viruses have captured a proto-oncogene (see below) from the cellular genome replacing part of the viral genome or adding it after the env gene. The captured proto-oncogene has become a viral oncogene or v-onc. The long terminal repeat or LTR (see Figure 12.1) is a strong promoter that can overexpress the v-onc gene leading to the development of tumor cells.
Order Ortervirales
Published in Paul Pumpens, Peter Pushko, Philippe Le Mercier, Virus-Like Particles, 2022
Paul Pumpens, Peter Pushko, Philippe Le Mercier
It is noteworthy that the Retroviridae members package dimers of the single-stranded, positive-sense, linear RNA genomes. In addition to the gag, pol and env genes, these viruses may have accessory genes, which are located between pol and env, downstream from the env, or within the env gene. Some retroviruses may carry genes called oncogenes or onc genes, which are known for their ability to cause tumors in animals and transform cells in a culture into an oncogenic state.
Acute and Chronic Transforming Retroviruses
Published in Pimentel Enrique, Oncogenes, 2020
The complete nucleotide sequence of the HTLV-I provirus genome integrated in human leukemia cell DNA has been determined and it was predicted that genome would code for 48-kd, 99-kd, and 54-kd proteins, corresponding to gag, pol, and env products, respectively.225 The complete LTR nucleotide sequences of American and Japanese isolates of HTLV-I have been compared and only a few differences exist between these virus isolates, which would represent strains of the same virus.197 In addition to these three genes, which are common to other chronic retroviruses, the HTLV genome contains a 1.5 kb region, the X region, located between the env gene, and the 3′ LTR. The X region can be divided into a 5′ nonconserved region and a 3′ highly conserved region designated LOR (long open reading frame).226 Comparison of the entire genomes of HTLV-I and BLV demonstrates an apparent relatedness of the two viruses, although there are some remarkable structural differences between them.227
Human endogenous retrovirus K (HERV-K) env in neuronal extracellular vesicles: a new biomarker of motor neuron disease
Published in Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, 2022
Yuan Li, Yong Chen, Nan Zhang, Dongsheng Fan
Douville et al. reported that HERV-K transcripts were increased in patients with ALS, especially in the prefrontal lobe (15). Li et al. (16) suggested that the expression of HERV-K was increased in autopsy brain tissue of patients with ALS compared to healthy controls and patients with Alzheimer's disease (AD). And env was increased selectively in the cytoplasm of pyramidal cells and spinal anterior horn cells but not in glial cells, white matter, hippocampal neurons and posterior cord. Cells transfected with HERV-K or the env gene all resulted in atrophy and shortened processes, which were concentration-dependent. Transgenic mice expressing the full-length or TM of env exhibited atrophy of the motor cortex and decreased protrusions of pyramidal cells. Therefore, HERVs, especially HERV-K env, may be used as a marker for the diagnosis and monitoring of disease progression in MND. There is an urgent need for a noninvasive technique to detect the expression level of HERVs derived from the central nervous system.
Clinical development of retroviral replicating vector Toca 511 for gene therapy of cancer
Published in Expert Opinion on Biological Therapy, 2021
Sara A. Collins, Ashish H. Shah, Derek Ostertag, Noriyuki Kasahara, Douglas J. Jolly
RRV, currently being evaluated clinically for the treatment of recurrent glioblastoma multiforme and colorectal cancer, are derived from amphotropic murine leukemia virus (MLV), a gammaretrovirus [20,21]. RRV have an intact MLV viral genome (including long terminal repeats [LTR], packaging signal (ψ), and genes gag, pol, and env), enabling vector replication. In addition, RRV carry a transgene cassette between the env gene and the 3ʹuntranslated region (3ʹ UTR). In most RRV described so far, transgene expression has been driven with an internal ribosome entry site (IRES, see Figure 1 a,b)but other expression systems have also been used successfully [22,23]. These vectors are unique compared to other oncolytic agents currently in development, as viral replication does not result in cell lysis. Rather, these vectors maintain viral persistence in tumors through the combined characteristics of non-lytic replication, stable integration into the cancer cell genome, and interferon-suppressive activity [24–28].
A clinical role for Förster resonance energy transfer in molecular diagnostics of disease
Published in Expert Review of Molecular Diagnostics, 2019
The rapid development of analytical techniques with extremely low limits of detection and emerging materials with superior photophysical properties (high brightness, photostability, large Stokes shift, narrow emission peak) have resulted in technologies that do not require amplification of nucleic acids [15]. Single-pair (sp)FRET techniques (analysis of single donor-acceptor pairs instead of many donor-acceptor ensembles) have been one major approach for accomplishing higher sensitivities [16,17]. Wabuyele et al. utilized spFRET in combination with a reverse molecular beacon (Cy5-to-Cy5.5 FRET pair) to detect a point mutation in the KRAS oncogene with 600 copies (50 aM) of human genomic DNA [18]. Nanomaterials such as QDs, metal NPs, graphene oxides, and upconversion NPs (UCNPs) have also been widely explored as FRET donors or acceptors for DNA or RNA based diagnostics. Zhang et al. showed that the QD-to-AF647 spFRET strategy with a 5 fM detection limit of target DNA was capable of detecting KRAS point mutations in clinical samples from ovarian cancer patients [19]. This method was later extended to a multiplexed format to detect the gap gene of HIV-1 and env gene of HIV-2 [20]. Such technologies are continuing to be improved for better sensitivity, specificity, and higher order multiplexing.