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Viral Pathogens: A General Account
Published in Jagriti Narang, Manika Khanuja, Small Bite, Big Threat, 2020
Vinod Joshi, Bennet Angel, Annette Angel, Neelam Yadav, Jagriti Narang
According to the Baltimore classification of viruses, Togaviruses fall under Group IV, which consists of single-stranded (+ve) RNA viruses. The family Togaviridae includes two genera: Alphaviruses and Rubiviruses. Their genome is linear and non-segmented and approximately 10,000–12,000 nucleotides long. The virus has an envelope and a nucleocapsid. It is icosahedral in shape constituted by 240 monomers. Glycoprotein spikes are found throughout the surface, which help to attach efficiently to the host cell surface (Fig. 3.2).
Introduction to virus structure, classification, replication, and hosts
Published in Avindra Nath, Joseph R. Berger, Clinical Neurovirology, 2020
Philippe Simon, Kevin M. Coombs
There is significant variability in the range of cell tropism for individual species of viruses. Some viruses (e.g., arthropod-borne togaviruses) are capable of infecting vertebrate animals of diverse orders such as humans and horses and of different classes such as birds and humans as well as the phylogenetically unrelated insects that vector the virus from one vertebrate host to the next. Other viruses may be extremely limited in their cell tropism. For example, the human retrovirus HIV is capable of infecting only some human-derived cells.
Interaction of Herpesviruses and Retroviruses
Published in Fred Rapp, Oncogenic Herpesviruses, 2019
Infection with two enteroviruses apparently produces phenotypically mixed virions very efficiently. Mixed infection of HeLa cells with poliovirus types 1 and 2 resulted in a 100% yield of doubly neutralizing virions.12 When poliovirus RNA was enclosed within a Coxsackie virus type Bl capsid, it penetrated and replicated for one cycle in poliovirus-resistant mouse cells.13 Single cells doubly infected with both echovirus type 7 and Coxsackie virus type A9 yielded phenotypically mixed virions with neutralizing properties of both parents.14 Single cells doubly infected with poliovirus type 1 and echovirus type 1 have been reported15 and evidence of doubly neutralizing virus particles was also found.16 The occurrence of phenotypic mixing among other RNA viruses, such as between related strains of togaviruses, has also been reported.17
Zika virus pathogenesis and current therapeutic advances
Published in Pathogens and Global Health, 2021
Caroline Mwaliko, Raphael Nyaruaba, Lu Zhao, Evans Atoni, Samuel Karungu, Matilu Mwau, Dimitri Lavillette, Han Xia, Zhiming Yuan
Currently, a few drugs, including Pinocembrin and BCX4430, also known as Galidesivir, have completed phase 1 clinical trials performed by Biocryst Pharmaceuticals. Galidesivir was administered intravenously in 24 healthy volunteers. In trials, this drug was shown to be safe and tolerable. Intramuscular administration and animal models have also been used to show that this drug has survival benefits against several pathogens, including Ebola [129], Marburg, YFV, WNV [127] and ZIKV [129]. Additionally, Galidesivir has shown broad-spectrum activity in vitro against more than 20 RNA viruses in nine different families, including filoviruses, togaviruses, bunyaviruses, arenaviruses, paramyxoviruses, coronaviruses, and flaviviruses [151]. Nevertheless, this drug has been shown to confer resistance as a result of an E460D substitution in the NS5 protein of TBEV [128], which represents a major challenge in the development of viral replication inhibitors since the viruses are rapidly evolving.
Toward the identification of ZDHHC enzymes required for palmitoylation of viral protein as potential drug targets
Published in Expert Opinion on Drug Discovery, 2020
Mohamed Rasheed Gadalla, Michael Veit
Protein palmitoylation was first described for a viral spike protein, the G-protein of vesicular stomatitis virus [32]. It rapidly turned out that (almost) every enveloped virus contains at least one S-acylated glycoprotein [33–35]. Basic biochemical features of S-acylation, such as the role of acyl-CoA as lipid donor and that fatty acid transfer is not specific for palmitate, were initially discovered with viral spike proteins [1,3,36,37]. Since they are synthesized in large amounts and can be purified from virus particles, mass spectrometry was feasible to determine the acyl chains attached to individual cysteines. We found that HA of Influenza B virus contains 97% palmitate attached to two cytoplasmic cysteine residues and HEF of Influenza C virus is predominantly stearoylated at one cysteine at the end of the transmembrane region (Table 1). HAs of Influenza A virus contain a mixture of palmitate and stearate, but stearate is exclusively attached to the cysteine positioned at the end of the transmembrane region, whereas the two cytoplasmic cysteines are acylated with palmitate [38,39]. Shifting the TMR cysteine to a cytoplasmic location virtually eliminated attachment of stearate indicting that the main signal for stearate attachment is the location of an acylation site relative to the transmembrane span [40]. Site-specific attachment of stearate at a transmembrane cysteine was also observed for E1 of togaviruses and F of a paramyxovirus [41]. Whether attachment of palmitate or stearate has functional consequences is not known. However, myristate (C14) and palmitate (C16), which also differ by only two methylene groups show a significant difference in their hydrophobicity, which has a profound effect on the affinity of the acylated peptide for lipids, only palmitate promotes efficient membrane binding [42,43]. In addition, the length of a covalently attached acyl chain might also influence the strength of protein–protein interactions [44].