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Zika: An Ancient Virus Incipient into New Spaces
Published in Jagriti Narang, Manika Khanuja, Small Bite, Big Threat, 2020
Bennet Angel, Neelam Yadav, Jagriti Narang, Surender Singh Yadav, Annette Angel, Vinod Joshi
Immature virions present in the cytoplasm contain a lipid membrane having prM, and envelope proteins are present on the surface in icosahedral fashion (Kostyuchenko et al., 2016). Trimers of prM-envelope protein heterodimers are formed for the translation and processing of viral polyproteins. prM translocation is assisted by C protein, which contains a site for RNA interaction and shows interaction due to C-terminal trans-domain and also serves as signal sequence. Immature virions become mature when they move around the low-pH environment of trans-Golgi network (Dai et al., 2016). In the low-pH environment, prM can be cleaved by host protease. There is change in the conformation of E protein dimer, and the remaining portion is still associated with the virions (Barba-Spaeth et al., 2016). Upon increase in pH, the mature virion separates from the pr peptide as the virion is exported from the cell using host secretory machinery. The mature ZIKV envelope protein has only one glycosylation at Asnl54, which makes it differ from the dengue virus envelope protein, which is glycosylated at two sites (Asnl53 and Asn57) (Haddow et al., 2012). The molecular pattern present on infected cells can be easily recognized by pattern recognition receptors (RIG-1/MDA5 and TLR3) induced by the innate immune response. It ultimately leads to the production of interferons (IFN-I and IFN-III) (Faye et al., 2014). Transmembrane IFN inducible proteins are expressed, which inhibit the replication of ZIKV. IFITM3 and IFITM1 have also been shown to inhibit the replication of ZIKV (Barba-Spaeth et al., 2016; Dai et al., 2016; Kostyuchenko et al., 2016; Sirohi et al., 2016) (Figs. 6.5 and 6.6).
Coronavirus disease 2019: investigational therapies in the prevention and treatment of hyperinflammation
Published in Expert Review of Clinical Immunology, 2020
Isabelle Amigues, Alexander H Pearlman, Aarat Patel, Pankti Reid, Philip C. Robinson, Rashmi Sinha, Alfred Hj Kim, Taryn Youngstein, Arundathi Jayatilleke, Maximilian Konig
Emerging information implicates impairment of the type I interferon response in the pathogenesis of severe COVID-19 infection. Blanco-Melo et al. found that SARS-CoV-2 impairs expression of type I and III IFN genes in a SARS-CoV-2 animal model as well as in lung tissue and sera from patients with COVID-19 [39]. Trouillet-Assant et al. examined the kinetics of the plasma IFN-I response in 26 critically ill patients with COVID-19 and found that all (5 out of 5) patients with sustained lack of IFN-α2 production required invasive ventilation compared to 9 out of 21 patients with the expected peak of IFN-α2 8–10 days after onset of symptoms; all patients had sustained elevation of C-reactive protein (CRP) and IL-6 levels [40]. Hadjadj et al. reported that plasma levels of IFN-α2 at 8–12 days after symptom onset were lower in 18 critically ill patients with COVID-19 than in 15 patients with mild-to-moderate symptoms [41]. Gene expression analysis also showed that ISGs such as MX1, IFITM1, and IFIT2 were downregulated, but serial measurements were not reported [41]. Taken together, these findings support the concept of delayed or impaired IFN responses causing delayed viral clearance and increased proinflammatory cytokine release, ultimately causing severe disease. While we are still striving to fully understand the pathophysiology of COVID-19, this model could explain part of the wide range of clinical presentations of SARS-CoV-2 infection.
DNA methylation changes on immune cells in Systemic Lupus Erythematosus
Published in Autoimmunity, 2020
Carolina Hurtado, Liliana Yazmín Acevedo Sáenz, Elsa María Vásquez Trespalacios, Rodrigo Urrego, Scott Jenks, Iñaki Sanz, Gloria Vásquez
In the first of these studies, methylation difference was found in 293 GC sites, of which 68% were hypomethylated and 32% hypermethylated. Within the genes with hypomethylation were IFITM1, IFIT3, DDX60, ISG15 and the two with the largest hypomethylation were MX1 and IFI44L, which are regulated by interferon. As a consequence, the expression of the mentioned genes was increased [69]. On the other hand, Sukapan et al. identified hypomethylation of LINE-1 (Long Interspersed Nuclear Elements) in neutrophils of patients with SLE. The genes with LINE-1 content were correspondingly over-expressed and were related to cellular functions such as apoptosis. Finally, no correlation was reported between methylation patterns of LINE-1 with disease activity measured by SLEDAI [70]. Also, LINE-1 appear to participate during the neutrophil differentiation process [71].
Zika virus, vaccines, and antiviral strategies
Published in Expert Review of Anti-infective Therapy, 2018
Sophie Masmejan, David Baud, Didier Musso, Alice Panchaud
Interferons (IFNs) signaling cascade is essential in the antiviral host response against flavivirus [64]. This has led to the hypothesis that IFNs could be a potential drug against ZIKV. IFN-alpha and -beta are considered compatible with pregnancy in all trimesters for appropriate indications [27,28]. Contreras et al. developed a mammalian cell-based culture model for ZIKV and showed that IFN-alpha, -beta, and -gamma inhibit ZIKV growth in this platform [65]. Later, utilizing a qRT-PCR assay, Goebel et al. showed that IFN-alpha had an antiviral activity in pretreated Vero cells [66]. Chan et al. tested IFN-alpha and -beta on mice, which showed attenuated weight loss and improved survival in addition to lower expression of ZIKV-NS1 protein in the blood, after having been challenged by ZIKV PRVABC59 [67]. Bowen et al. challenged these results on human dendritic cells, showing that IFN had only a modest effect on ZIKV, suggesting that ZIKV could evade the type 1 IFN response [64]. Savidis et al. studied IFITM1 and IFITM3 (IFN-inducible transmembrane proteins) and showed they were able to inhibit infection in HeLa cells [68]. In addition to the molecules above, Van Der Hoek et al. interestingly showed that expression of Viperin, an IFN-stimulated gene that has a known effect against other viruses, resulted in impairment of ZIKV replication in cultured cells [69].