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HIV-Integrase
Published in Mihai V. Putz, New Frontiers in Nanochemistry, 2020
Corina Duda-Seiman, Daniel Duda-Seiman, Mihai V. Putz
In the early stages of lifecycles of retroviruses, the viral RNA genome is converted into a DNA provirus. When entering into a host cell (infected cell), the intracytoplasmatic transcription stage of viral RNA is initiated in order to form a linear double-stranded DNA molecule with long terminal repeats (LTR) with the possibility of intra-chromosomial DNA integration (Bowerman et al., 1989). Viral integrase was considered an attractive and promising target for therapy: HIV viruses are not able to replicate without integration into a host chromosome (De Clercq, 2002). HIV-1 integrase (Mr 32000) is encoded at the 3′-end of the pol gene. Integration of HIV DNA into the host cell genome comprises certain DNA cleavage and coupling reactions; to be noticed that the viral cDNA is initially modeled in the host cell cytoplasm, and afterward, it is integrated into the nucleus. This step depends on the entirely functional HIV-integrase. (Nair and Chi, 2007). A particular aspect of HIV integration is the accumulation of increased volumes of unintegrated viral DNA in the infected cells, being considered a significant issue of the viral cytopathic effect. (Faucci, 1988).
Selection and Application of Catalytically Active Oligonucleotides
Published in Rakesh N. Veedu, Aptamers, 2017
Rachel Gysbers, Kha Tram, Sepehr Manochehry, Dingran Chang, Yingfu Li
DNAzymes are also being developed as therapeutics for viral diseases such as HIV and hepatitis (Table 4.3). Targeting different regions of the HIV genome with DNAzymes allows for inhibition at different stages of the HIV life cycle. For example, HIV integrase is an enzyme that is responsible for integration of the proviral genome into the human genome and this integration step is the first step of the virus hijacking the human cell machinery for its propagation and replication. RNA-cleaving DNAzymes were shown to suppress integrase expressions through sequence-specific mRNA cleavage [138].
Proteins and proteomics
Published in Firdos Alam Khan, Biotechnology Fundamentals, 2018
Some viruses (such as HIV, the cause of AIDS) have the ability to transcribe RNA into DNA. HIV has an RNA genome that is duplicated into DNA. The resulting DNA can be merged with the DNA genome of the host cell. The main enzyme responsible for the synthesis of DNA from an RNA template is called reverse transcriptase. In the case of HIV, reverse transcriptase is responsible for synthesizing a complementary DNA strand (cDNA) to the viral RNA genome. An associated enzyme ribonuclease H digests the RNA strand, and reverse transcriptase synthesizes a complementary strand of DNA to form a double helix DNA structure. This cDNA is integrated into the host cell’s genome via another enzyme (integrase) causing the host cell to generate viral proteins, which reassemble into new viral particles. Subsequently, the host cell undergoes programmed cell death called apoptosis. Some eukaryotic cells contain an enzyme with reverse transcription activity called telomerase. Telomerase is a reverse transcriptase that lengthens the ends of linear chromosomes. Telomerase carries an RNA template from which it synthesizes DNA repeating sequence, or “junk” DNA. This repeated sequence of DNA is important because every time a linear chromosome is duplicated, it is shortened in length. With “junk” DNA at the ends of chromosomes, the shortening eliminates some of the nonessential, repeated sequence rather than the protein-encoding DNA sequence farther away from the chromosome end. Telomerase is often activated in cancer cells to enable cancer cells to duplicate their genomes indefinitely without losing important protein-coding DNA sequence. Activation of telomerase could be part of the process that allows cancer cells to become technically immortal. However, the true in vivo significance of telomerase has still not been empirically proven.
Optimal control in a multi-pathways HIV-1 infection model: a comparison between mono-drug and multi-drug therapies
Published in International Journal of Control, 2021
Chittaranjan Mondal, Debadatta Adak, Nandadulal Bairagi
Transmission of HIV-1 within a host may be possible through two modes, viz. cell-free mode and cell-to-cell mode (Hübner et al., 2009; Iwami et al., 2015; Zhong, Agosto, Munro, & Mothes, 2013). In cell-free transmission mode, free plasma virus infects the healthy cells. In this transmission process, a virus is attached to the receptor and co-receptor of healthy cell with gp120 spikes and join the host cell with the help of gp41 protein of HIV. Neutralizing antibodies can significantly affect this binding process (Zhong, Agosto, Ilinskaya, et al., 2013). After successful viral entry, the virus life cycle is completed using the host cell's machineries. First, viral RNA is transcribed into DNA with the help of reverse transcriptase enzyme of virus and it is then integrated into cell's chromosome with the help of integrase enzyme. Using the enzyme RNA polymease of the host cell, HIV makes messenger RNA and long chains of viral particle are produced using the host's enzyme. The viral protease enzyme then cuts the long chains of HIV proteins into smaller individual proteins. At the final stage, newly formed virus particles are released through cell lysis (Adamson & Freed, 2007).
Predicting algorithm of attC site based on combination optimization strategy
Published in Connection Science, 2022
Zhendong Liu, Xi Chen, Dongyan Li, Xinrong Lv, Mengying Qin, Ke Bai, Zhiqiang He, Yurong Yang, Xiaofeng Li, Qionghai Dai
The attC site is the main site for site specific recombination, and its bottom strand is folded into a hairpin-like structure and recombined as a single strand (Figure 1). The attC site can mediate the insertion and excision of gene cassettes under the catalysis of integrase. The excision of the gene cassette mainly occurs between two adjacent attC sites on the integrative system, and the insertion of the gene cassette involves the attC site on the gene cassette and the attI site on the integrative system (Figure 2).
Three-step synthetic procedure to prepare dolutegravir, cabotegravir, and bictegravir
Published in Green Chemistry Letters and Reviews, 2022
Xianheng Wang, Song Chen, Hanqi Cui, Yuqi He, Changkuo Zhao
AIDS remains a serious global public health threat to humans even in modern society. With the development of science and technology, it has been found that integrase plays an important role in the replication of HIV-1 virus, and this enzyme has become an attractive drug target over the past few years (1). So far, a lot of integrase inhibitors including raltegravir, elvitegravir, dolutegravir, cabotegravir, and bictegravir have been launched globally or approved to enter into phase III clinic trials (Figure 1) (2–4).