Neuroviral Infections
Sunit K. Singh, Daniel Růžek in Neuroviral Infections, 2013
The phenomenon of viral tropism to certain types of cells and tissues is determined by specific cell surface receptors. These receptors are normal constituents of the cytomembrane, which play key roles in normal cell physiology, but they may also be used by viruses for their attachment to and entry into the cell, thus having decisive roles for tissue tropism and virus host range. For the binding of a virus to a cell receptor, certain structures on the virus surface—the envelope glycoproteins in enveloped viruses, the nucleocapsid proteins in nonenveloped viruses, and the viral attachment proteins—have an equally important role. Definite cell surface receptors may allow attachment for several types of viruses, and, on the other hand, definite types of viruses may be attached to several types of receptors.
Measles and its neurological complications
Avindra Nath, Joseph R. Berger in Clinical Neurovirology, 2020
One of the most important characteristics determining viral tropism is the usage of specific receptors on the surface of susceptible target cells that allow viral attachment and penetration. MV is highly species specific in that it does not naturally replicate in nonprimate hosts. In vivo it reveals a pronounced tropism for cells of the hematopoietic lineage and epithelial cells. Multinucleated giant cells are formed in lymph nodes. They are pathognomonic for the measles infection. However, endothelial cells and neural cells such as neurons, astrocytes and microglial cells can also be infected. As cellular receptors for MV, the widely expressed transmembrane protein CD46 [12,13], the lymphoid cell specific signaling lymphocytic activation molecule (SLAM, CD150) [14,15], and the epithelial cell-specific receptor nectin-4 [16,17] have been identified. In contrast to CD46, which is utilized by vaccine and lab-adapted MV strains, all wild-type strains and isolates interact with CD150 on the surface of activated B and T cells, dendritic and memory cells, and with nectin-4 on epithelial cells.
Recombinant DNA Technology and Gene Therapy Using Viruses
Patricia G. Melloy in Viruses and Society, 2023
Some common characteristics to consider when picking a viral vector for gene therapy include how long and where you want the virus to drive expression of a gene, whether the virus can replicate inside the cell, what the risk is of causing a change in the genome if it is an integrating virus, and what the likelihood is that the virus itself will activate the immune system (Kurreck and Stein 2016). Different applications favor different characteristics. In some cases, you may not want the virus to replicate if your goal is to correct a monogenic disease, but replication might be all right if are trying to create an oncolytic virus to go after the rogue dividing cells (Kurreck and Stein 2016). Sometimes a viral vector is chosen based on its “tissue tropism.” For example, many types of AAVs target different organs ranging from the liver, heart, and skeletal muscle to other organs (Kurreck and Stein 2016). For example, AAV9 can cross the blood-brain barrier, meaning that potentially it can be used to treat neurological disorders (Wang, Tai, and Gao 2019). However, it should be noted that AAVs are not found to cause human disease on their own and are not capable of their own replication (Dunbar et al. 2018; Wang, Tai, and Gao 2019; Li and Samulski 2020).
The dawn of precision medicine in HIV: state of the art of pharmacotherapy
Published in Expert Opinion on Pharmacotherapy, 2018
Ying Mu, Sunitha Kodidela, Yujie Wang, Santosh Kumar, Theodore J. Cory
CCR5 antagonist test and HLA-B*5701 allele test are two other lab tests recommended by FDA for ART administration. Identifying the pharmacogenetics of patients’ is another way to apply for the precision medicine. Patients with the HLA-B*5701 allele are at a higher risk of hypersensitivity to react with abacavir. HLA-B*5701 screening is recommended prior to prescribing abacavir. GT of viral tropism is widely used in the clinical settings to test patient’s [171] dominant virus population. The genetic test of CYP2B6 516 G > T is useful to identify side effects of patients using efavirenz. UGT1A1*28 testing prior administration of ATV can reduce the risk of hyperbilirubinemia. These current tests in the clinic are essential to practice precision antiretrovirals. However, improvements are in need: patients’ genetic tests are not always available, and the tests can be costly and time consuming. Furthermore, drug response may be effected by multiple genes and not just the one code for the specific protein. These tests reduce the risk of side effects and improve drug efficacy, but going forward will require knowledge of genetic risk factors and the development of new DNA technologies. With advanced knowledge of the human genome and new technologies, including DNA microarrays, DNA chips, and human genome analysis, in the future patients’ specific gene characteristics will be basic information for physicians to choose drug combinations, optimizing drug concentration and minimizing the side effects.
Lactoferrin for Mental Health: Neuro-Redox Regulation and Neuroprotective Effects across the Blood-Brain Barrier with Special Reference to Neuro-COVID-19
Published in Journal of Dietary Supplements, 2021
Sreus A. G. Naidu, Taylor C. Wallace, Kelvin J. A. Davies, A. Satyanarayan Naidu
SARS-CoV-2 could infect the brain through neuroaxonal and hematogenous modes of transmission. The neuroaxonal transmission includes nasal (olfactory nerve track), ocular (optic nerve tract), and gastrointestinal (vagus nerve track) routes by trans-synaptic transfer via brain stem (Jakhmola et al. 2020). The hematogenous transmission is mainly through the pulmonary/circulatory routes via the BBB. Receptor recognition is the first step of viral infection, a key determinant of host cell/tissue tropism. Coronaviruses have evolved several complex host cell surface receptor recognition patterns. Angiotensin-converting enzyme 2 (ACE2) is a potential receptor for SARS-CoV-2 cellular docking and entry (Hoffmann et al. 2020), and ACE2 is widely expressed on various brain cells and cerebral regions. The resident CNS cells such as astrocytes and microglia also express ACE2; thereby, provide potential docking sites for viral attachment/entry into the brain (Jakhmola et al. 2020). A recent study reported that neuropilin-1 (NRP1), known to bind furin-cleaved substrates, could potentiate SARS-CoV-2 infection (Cantuti-Castelvetri et al. 2020). NRP1 is abundantly expressed in the respiratory and olfactory mucosa, with highest expression in endothelial and epithelial cells. Furthermore, SARS-CoV-2 also recognizes four other putative receptors on host cells; and binds to proteoglycans such as heparan sulfate via lectin-type interactions. Versatility in cell surface receptor interactions makes SARS-CoV-2 a multi-tropic viral pathogen (Naidu et al. 2020a).
Coronavirus disease – COVID-19: new perceptives towards epidemic to pandemic
Published in Journal of Drug Targeting, 2020
S. B. Santhosh, A. Mohamed Sheik Tharik, M. Susitra Manjari, R. Balakrishnan, N. Muruganandam, M. J. N. Chandrasekar
Suspected human case samples from COVID-19 were subjected to nucleic acid amplification tests (NAAT). Although a good contact history, systemic symptoms and radiographic changes of pneumonia make the diagnosis likely, the laboratory diagnosis, however, is more reliable. Specimen collections from the symptomatic patients and contacts are presented in Table 1. NAAT tests have been routinely carried out to confirm the causative viruses from upper and lower tract respiratory secretions [25,26]. All through COVID-19 transmission events, the confirmation cases of the virus are based on the NAAT such as real-time reverse transcription polymerase chain reaction (rRT-PCR) that served as the primary clinical laboratory diagnostic test [18,19,27,28]. Success of these tests is very important to understand the viral kinetics and tissue tropism found in virus patients. Definite and sensitive assays targeting RdRP, N, E genes of SARS-CoV genome were intended to identify the viral RNA in clinical specimens [26]. Lower respiratory tract (LRT) samples give high viral loads [29]. Various sampling source or different operations may influence the RT-PCR test report. At an early stage of the virus around 60% of throat swab samples were reported as positive [30].
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