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HIV neurological complications
Published in Avindra Nath, Joseph R. Berger, Clinical Neurovirology, 2020
In addition to structural proteins, the HIV viral genome encodes regulatory and accessory proteins that govern the viral replication process [20]. The regulatory proteins act in the cell nucleus, either promoting the elongation phase of HIV transcription (Tat) or activating the export of unspliced RNA (Rev). The accessory proteins have multiple functions including downregulation of CD4 cell surface receptors (Nef, Vpu), modulation of the cell cycle and viral DNA nuclear import (Vpr) [21], and degradation of cellular antiretroviral factors (Vif) [22].
HIV-2
Published in Niel T. Constantine, Johnny D. Callahan, Douglas M. Watts, Retroviral Testing, 2020
Niel T. Constantine, Johnny D. Callahan, Douglas M. Watts
The major regulatory genes tat and rev appear analogous in HIV-1 and HIV-2, although they may vary more in the HIV-2 virus. However, one of the regulatory components, vpx (pl6), is present in HIV-2 but not in HIV-1; it is similar in function to the vpu of HIV-1, may be responsible for determining which cells are infected with the virus, and may be responsible for the different pathologic effects noted with HIV-2 infection. Antibody responses to vpx have been detected in about 14% of HIV-2-infected individuals. This may have important diagnostic application, since the detection of antibodies to vpx will identify HIV-2 infection, especially when sera react by both assays. Antibodies to the nef regulatory protein, which may not function as a down regulator in HIV-2, have been detected in about 25% of HIV-2-infected individuals. Sera that contain HIV-1 antibodies have no neutralizing affect on HIV-2 isolates, which contrasts with the cross-neutralizing activity of HIV-2 sera on HIV-1 isolates.
The Acquired Immunodeficiency Syndrome (AIDS)
Published in Constantin A. Bona, Francisco A. Bonilla, Textbook of Immunology, 2019
Constantin A. Bona, Francisco A. Bonilla
The vif gene product facilitates virus release and increases viral particle infectivity. It may act as a cysteine protease on the Env protein. Vpu facilitates budding of the virus. This protein is not a component of the mature virion, but the ability of HIV to infect other cells depends on its activity. The vpr gene product is contained in virus particles. This molecule enhances viral replication, but the mechanism is unknown.
Important role of microglia in HIV-1 associated neurocognitive disorders and the molecular pathways implicated in its pathogenesis
Published in Annals of Medicine, 2021
A. Borrajo, C. Spuch, M. A. Penedo, J. M. Olivares, R. C. Agís-Balboa
Direct HIV-mediated neurotoxicity is related to the interaction between neurons and viral proteins gp120, viral surface glycoprotein 41 (gp41), negative regulatory factor (Nef), Tat, Vpr, and Viral protein U (Vpu), resulting in neuronal injury or apoptosis and contributing to CNS pathology (Figure 1) [76]. During the process of HIV entry into host cells, the viral envelope proteins gp120 and gp41 may damage other neurons in close proximity to them. More of these damaging viral proteins are released when viral replication is high leading to the release of viral particles from these infected cells [77] through a direct mechanism involving the induction of ROS production and increased cell death [78–81]. Elevated levels of ROS increases DNA nucleic acid oxidation, causing DNA instability, and also inhibits DNA repair by eliminating DNA glycosylase 1 [82]. Gp120 and Tat further contribute to neurotoxicity by increasing lipid peroxidation, leading to the accumulation of ceramide [83]. Vpr protein provokes G2/M arrest and plays a role in the infection of macrophages [84], HIV transcription, and apoptosis [85,86]. Finally, Vpu induces virion release by preventing the action of host restriction factors [87,88], downregulating CD4 during the late stages of HIV-1 infection [89], and impeding Nuclear factor-kappa-light-chain-enhancer of activated B cells (NF-κB) activation [89,90].
Antiviral therapy for the sexually transmitted viruses: recent updates on vaccine development
Published in Expert Review of Clinical Pharmacology, 2020
Kimia Kardani, Parya Basimi, Mehrshad Fekri, Azam Bolhassani
HIV causing AIDS has become one of the most serious problems in health since the first cases were reported in 1981 [208]. HIV was grouped to the genus Lentivirus, the family of Retroviridae, and the subfamily Orthoretrovirinae. The full length HIV genome is encoded on 9.5 kb RNA strand [209]. Based on geographical origin, genetic characteristics, organization of genome and differences in the viral antigens, HIV-1 and HIV-2 were differentiated in the world. The HIV-1 was divided into groups M, N, O and P [210]. M group of HIV-1 was further divided into A-D, F-H, J and K subtypes. The present global epidemic has occurred by M group more than N and O groups. The HIV-1 is more common than HIV-2 in the world. HIV-2 was identified in West Africa region. The majority of the people in America, Europe, Asia and Australia were infected with the subtype B of M group. The subtypes A, C and D of M group were observed in Africa [211]. In Argentina, most people were infected with BF recombinant forms. The recombination was found when a target cell was infected with two different HIV subtypes [212,213]. The HIV genome encodes 16 viral proteins which play essential roles during the HIV life cycle. The gag, pol, and env major genes express the structural proteins (i.e. matrix, capsid, nucleocapsid and p6), the viral enzymes (i.e. reverse transcriptase, protease, and integrase), and the envelope proteins (gp120 and gp41), respectively. Other genes express the accessory proteins (i.e. Vif, Vpu/Vpx, Vpr and Nef), and the regulatory proteins (i.e. Tat and Rev) [214].
In Silico and in Vivo Analysis of HIV-1 Rev Regulatory Protein for Evaluation of a Multiepitope-based Vaccine Candidate
Published in Immunological Investigations, 2022
Samaneh H. Shabani, Kimia Kardani, Alireza Milani, Azam Bolhassani
Since the first determination of binding motifs for T-cell antigens by Rammensee et al., epitope selection has been extensively developed by algorithms of epitope prediction (Falk et al. 1991). Some studies evaluated the development of in silico prediction of potential MHC class I and class II-restricted epitopes against various pathogens such as HIV-1 (Kardani et al. 2020). The fact that there is no FDA approved vaccine against HIV-1 infection make scientists to rethink about developing a potent and effective vaccine. Nowadays, new approaches such as the use of immune-informatics have been utilized in the field of vaccine design to save time and cost (Chiarella et al. 2009; Slingluff 2011). Multiepitope subunit vaccines can enhance the specificity of the target, ease in production, safety, and rate of accuracy (Sahni and Nagendra 2004; Slingluff 2011). For example, one study identified 27 conserved, multiple HLA-DR-binding peptides in HIV-1 Gag, Pol, Nef, Vif, Vpr, Rev and Vpu proteins. Mice immunization showed T-cell proliferation and subsequently IFN-γ and TNF-α secretion (Almeida et al. 2012). In another study, mice immunization with multiepitope construct harboring the 18 HIV-1 CD4+ epitopes induced the proliferation of T cells and the secretion of effective cytokines (Rosa et al. 2011). Fusion of the 8 HIV-1 CD4+ epitopes derived from P6, P17, Pol, Gp160, Rev, Vpr, Vif and Nef proteins to the heavy chain of αDEC205 efficiently enhanced immunity versus HIV-1 infection, as well (Apostólico et al. 2017). In a clinical report, the CD8+ T cell responses were found up to 19 and 37% of HIV-1 patients against overlapping peptides derived from Tat and Rev proteins, respectively (Addo et al. 2001). Moreover, the cellular and humoral responses were elicited in 45% of tested subjects by a peptide-based vaccine comprising a cocktail of T-cell epitopes of the conserved Rev, Vif, Vpr, and Nef sequences in a phase II clinical trial (Boffito et al. 2013).