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The Viruses
Published in Julius P. Kreier, Infection, Resistance, and Immunity, 2022
The replication process in the RNA tumor viruses is unique. The single-stranded viral RNA template is used to produce an initial DNA-RNA hybrid, which is then converted by DNA polymerase into a double stranded DNA linear intermediate. The DNA intermediate integrates into the host cell DNA and is referred to as a “provirus.” The provirus is transcribed into both viral messenger and viral genomic RNA. The RNA viruses containing reverse transcriptase were named the Retroviridae (Table 16.1) in recognition of the retrograde flow of genetic information from RNA into DNA. Retroviruses are known to infect a wide variety of animals, including humans, and are associated with certain types of cancer. They may also induce immunosuppressive or immune-mediated diseases, or may exist as stable members of the host germ line.
Genetic Manipulation of Human Marrow: Gene Transfer Using Retroviruses
Published in Adrian P. Gee, BONE MARROW PROCESSING and PURGING, 2020
Philip Hughes, R. Keith Humphries
The advantages conferred by using retroviruses as a gene transfer vehicle stem from their unique life cycle.1–3 Retroviruses are single-stranded RNA viruses that infect cells by the interaction of the viral envelope protein with specific cell surface receptors. Once the viral genomic RNA has entered the cytoplasm, it is reverse transcribed into double-stranded DNA by enzymes supplied by the virus. This double-stranded DNA copy of the viral genome, or provirus, is then integrated, again under the control of viral proteins, into the cell’s DNA. Once part of the cell’s genome, the provirus transcribes messenger RNA from its three genes: gag, pol, and env, and these are used to produce the viral core proteins, enzymes, and envelope proteins. The provirus also produces a genomic length RNA which is assembled into the core, along with the retroviral enzymes, and the core then buds from the cell membrane at a site where the viral envelope proteins have been embedded. The proviral activities do not disrupt the cellular machinery and the cell continues to live.
Human T lymphotropic virus type 1 (HTLV-1)
Published in Avindra Nath, Joseph R. Berger, Clinical Neurovirology, 2020
Utilizing an HTLV-1 specific reverse transcriptase and integrase, HTLV-1 transcribes a DNA copy of its genome and integrates it into host DNA. The integrated virus is then known as provirus. Both sense and antisense orientation code for viral proteins. These include gag, pol, and env genes shared by all retroviruses, as well as tax, which plays an important role in activation of host genes, rex which controls splicing of the viral mRNA, and a more recently described anti-sense transcript protein HBZ, which maintains the transformed phenotype. Viral proteins promote clonal expansion of infected cells. Clonal expansion allows for higher fidelity in viral gene replication than de novo error-prone reverse transcription [12].
Pathogenicity and virulence of human T lymphotropic virus type-1 (HTLV-1) in oncogenesis: adult T-cell leukemia/lymphoma (ATLL)
Published in Critical Reviews in Clinical Laboratory Sciences, 2023
Sanaz Ahmadi Ghezeldasht, David J. Blackbourn, Arman Mosavat, Seyed Abdolrahim Rezaee
Surprisingly, many of those clones in ATLL (around 56%) have two different types of defective provirus, with a higher frequency of type 2 defective HTLV-1 (43%) [98]. Defective provirus type 2 cannot express Tax due to the deletion of the 5′ LTR or the deletion of the second exon. However, the HBZ sequence remains intact and frequently expressed [99]. These types of provirus are integrated into the host genome and seem to comprise a higher number of infected clones than those with complete proviruses. A defective virus may exist via: (1) Tax silencing to evade the host immune responses; (2) gene nonsense mutation or insertion and deletion; (3) LTR loss in 5′-end; and (4) 5′-LTR DNA methylation, which is discussed in various studies [19,100–102]. These clones containing defective HTLV-1 are more proliferative than those intact [90]. Most authors suggest a single integrated HTLV-1 provirus in infected cells, while an in vivo study could not exclude the possibility that some clones have more than one integrated provirus, particularly in the ATLL transformed clones [57,93]. Therefore, it is practically impossible to ignore the role of defective HTLV-1 proviruses in the pathogenesis of HTLV-1-associated diseases. Moreover, in acute and lymphomatous types of ATLL, the frequency of defective provirus was very high compared to the chronic types, demonstrating a close relationship between defective viruses and the progression of aggressive diseases.
Current status of COVID-19 vaccination: safety and liability concern for children, pregnant and lactating women
Published in Expert Review of Vaccines, 2022
Swagat Kumar Das, Manish Paul, Bikash Chandra Behera, Hrudayanath Thatoi
Nonetheless, the downside of this sort of vaccine is that the vaccine’s effectiveness is negatively affected by the vector immunity and the type of vector chosen. The advantage of vaccine candidates developed using replicating viral vectors is that the immune system is stimulated similar to natural infection. However, the disadvantage is the low vaccine production as only one or fewer copies of provirus are expressed per cell. The expression of proviruses is sensitive to chromosomal position effects as well as DNA repeats and introns. In the development of live attenuated vaccines, a simple technique is employed in conjunction with existing infrastructure. The downside of generating this form of vaccination is that it takes time to create the infectious clones for attenuated coronavirus because of its large genome size. Aside from that, considerable safety testing is required during the vaccine’s development. Like a live attenuated vaccine, inactivated vaccine development also follows a straightforward method utilizing existing infrastructure. This vaccine has been tested in humans to treat SARS-CoV-1 infection. In this vaccine development, adjuvants can be used for increasing immunogenicity. Handling huge volumes of infectious viruses and ensuring the integrity of antigen or epitope are key difficulties during vaccine production.
Aiming for protective T-cell responses: a focus on the first generation conserved-region HIVconsv vaccines in preventive and therapeutic clinical trials
Published in Expert Review of Vaccines, 2019
Curative strategies for HIV-1 infection have experienced increased interest and investments. As for sterile cure, it will never be possible to routinely purge every single integrated functional provirus from the body and no assay will ever be sensitive enough to definitely rule out the provirus presence. In contrast, a functional cure (immune control without LR eradication) or a hybrid cure (LR reduction with improved immune control), which would prevent both AIDS and onward HIV-1 transmission, might be more a realistic goal [102]. An HIV cure explores many approaches and the currently most pursued is the ‘kick-&-kill’ strategy [103]. It aims to expose the latent HIV-1 through latency reverting agents (LRA) and kill the cells with reactivated virus by augmented immune effector functions. Induction of effective killer T cells is, therefore, high on the priority list.