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Anti-HIV Agents
Published in Mihai V. Putz, New Frontiers in Nanochemistry, 2020
There are several proteins involved with the HIV virion entry process. They are: CD4 – a protein receptor found on the surface of the helper T Cells of the human immune system.gp120 – an HIV protein that binds to the CD4 receptor.CXCR4 and CCR5 – chemokine co-receptors found on the surface of the Helper T Cells and macrophages.gp41 – an HIV protein that penetrates the host cell’s membrane.
Dendrimers as a Candidate for Microbicide in Prevention of HIV-1 Infection in Women: Steps toward Their Clinical Evaluation
Published in Costas Demetzos, Stergios Pispas, Natassa Pippa, Drug Delivery Nanosystems, 2019
Daniel Sepúlveda-Crespo, Jose Luis Jiménez-Fuentes, María Angeles Muñoz-Fernández
The HIV-1 life cycle is a multistep process that depends on sequential interactions between viral and host cell factors that can be divided into six stages, as follows: Virus entry into the host cells: The first steps in the HIV-1 entry are the binding of HIV-1 gp120 to CD4 on the surface of T-helper lymphocytes or macrophages and a series of conformational changes in gp120. Initially, the D1 domain of CD4 joins the CD4-binding site of gp120, a highly conserved carbohydrate-free region. Then, the V1/V2 domain of gp120 modifies its position and its flexibility and the V3 loop extends away from the virion spike and is positioned toward the cell membrane to interact with CCR5 or CXCR4 coreceptors. Therefore, the V3 loop is the main domain involved in this interaction and V3 amino sequences determine the coreceptors used by HIV-1 for entry into the host cell [56]. The binding of gp120 to coreceptors, which involves two sequential interactions: The N-terminus of CCR5 or CXCR4 binds to the V3 loop, altering its conformation and facilitating the second interaction, with the extracellular loops of coreceptors that are critical for HIV-1 entry. These conformational changes allow the heptad repeat regions HR1 and HR2 to undergo an energetically favorable arrangement into a six-helix bundle where the HR1 domains form a central coiled-coil and the HR2 domains wrap around in an antiparallel direction. The proximity between cellular and viral membranes allows gp41 fusion and the entry of the viral capsid into host cells [56]. Finally, the location of the viral entry may or may not require the endocytosis of viral particles for full fusion [57]. In summary, the entry of HIV-1 involves binding of gp120 to CD4, followed by its binding to the coreceptor. This sequential binding leads to the release of gp41, with the subsequent fusion of the viral and host membranes [58, 59].Reverse transcription: The RT catalyzes the formation of a double-stranded viral DNA using the viral RNA as a template [60]. The newly synthesized proviral DNA is the substrate for the integration process.Integration: The viral DNA moves into the nucleus, and the IN catalyzes its integration into the host’s genomic DNA [61]. The integrated viral DNA can reversibly remain latent in an unproductive infection or can undergo active virus production.Transcription and translation: The integrated DNA is transcribed into a viral RNA, and it is translated into a long-chain polypeptide. The long polypeptide is then dissected into smaller individual proteins by the PR and undergoes further modifications to become functional [62].Viral assembly, budding, and maturation: Viral proteins and two single-stranded viral RNAs are assembled, and new virions are released out of host cells, which convert the immature virion into mature infectious HIV-1 [63].
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).