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Bunyaviruses
Published in Sunit K. Singh, Daniel Růžek, Neuroviral Infections, 2013
Patrik Kilian, Vlasta Danielová, Daniel Růžek
The accumulation of viral proteins, maturation and budding of viral particles leads to Golgi apparatus fragmentation and a breakdown of the cell secretory pathway (Salanueva et al. 2003). These processes result in cell death. However, in mosquito cells the situation is completely different. Here, the massive synthesis of viral proteins in the primary phase is followed by a recession, and the infection goes into a persistent phase (Scallan and Elliott 1992). During the primary phase of the infection in mosquito cells in vitro, the cells become highly mobile and form projections that connect to other cells. Structures such as microtubules, mitochondria, GA, and lysozymes can be seen in the projections. The viral nonstructural protein NSm was also observed inside these structures. However, it seems that NSm does not enter uninfected cells via the projections. The most probable function of the structures is to deliver warning signals to uninfected cells. Generally, the formation of complexes consisting of N and L viral proteins is considered to be the first phase of persistent infection (López-Montero and Risco 2011). A similar situation can be observed in mammalian cells when the interferon-induced antiviral protein MxA combines with viral protein N and formed complexes are accumulated in the perinuclear area. Since N protein is required for viral replication, its aggregation limits its utilization for viral multiplication (Kochs et al. 2002). Nevertheless, similar proteins that are responsible for the aggregation of L and N proteins in mosquito cells have not yet been identified.
Preadmission use of inhaled corticosteroids and risk of fatal or severe COVID-19: a meta-analysis
Published in Journal of Asthma, 2022
Chia Siang Kow, Syed Shahzad Hasan
Although our findings assured the safe use of inhaled corticosteroids during the COVID-19 pandemic, at the same time they challenged the hypothesis that inhaled corticosteroids could be a therapeutic intervention for patients with COVID-19 (7). Preclinical data found that the inhaled corticosteroids ciclesonide and mometasone, blocked the replication of severe acute respiratory syndrome coronavirus 2 by targeting viral nonstructural protein 15 (8). Hence, it seems from our meta-analysis that preclinical evidence does not translate into real-world clinical efficacy. However, included studies are of retrospective design, with different extents of adjustment of potential confounders in the respective studies. We await future studies with prospective designs to substantiate our findings.
Platelet–leukocyte interactions in the pathogenesis of viral infections
Published in Platelets, 2022
Eugenio D. Hottz, Anna Cecíllia Quirino-Teixeira, Laura Botelho Merij, Mariana Brandi Mendonça Pinheiro, Stephane Vicente Rozini, Fernando A. Bozza, Patrícia T. Bozza
It has been demonstrated that platelets can internalize DENV through DC-SIGN and heparan sulfate proteoglycans [26]. Moreover, DENV-infected platelets sustain viral genome translation and replication [26,27,64]. However, DENV-infected platelets are not capable of secreting new viral particles [27,64], implicating that platelets produce an abortive replication cycle. Despite the abortive infection, DENV engagement to DC-SIGN induces both platelet activation and apoptosis in vitro [41], which are also increased in platelets from patients [41,65]. Recently, we have reported that activation of DENV-infected platelets depends on viral genome translation with secretion of the viral nonstructural protein 1 (NS1), a TLR4 ligand [27]. These reports highlight that DENV activates platelets through receptor attachment and viral internalization leading to an abortive replication cycle that triggers platelet thromboinflammatory responses by generating viral PAMPs, such as NS1, and engaging innate immune receptors, such as TLR4. Aside from DC-SIGN, it has been reported that DENV activates platelets through mechanisms involving CLEC2 [37], but whether interaction through CLEC2 leads to virus internalization and replication remains unknown.
Asthma in the era of SARS CoV-2 virus
Published in Journal of Asthma, 2022
Agamemnon Bakakos, Anastasia Krompa
In a recent in vitro study, ICS were even reported to have a protective effect against the novel virus, especially ciclesonide and mometasone, by inhibiting the replication of the viral nonstructural protein 15 (NSP-15) in MERS and SARS-CoV-2. However, the generation of resistant mutations might preclude clinical effect (24). Similar results were reported in another in vitro study, as Yamaya et al. demonstrated that budesonide paired with bronchodilators, either formoterol or glycopyronium, can act protectively against the coronavirus HCov-229E by halting its replication and cytokines production. Regarding OCS, data is still scarce due to the small number of patients who still rely on them for severe asthma control. Most severe asthmatics presenting a T2 high endotype are able to reduce or even stop OCS with the use of biologics that are corticosteroid sparing such as omalizumab, mepolizumab, benralizumab and dupilumab (25). After early skepticism over the use of corticosteroids, the RECOVERY trial enrolled a total of 6,425 coronavirus positive hospitalized patients who were divided in groups that received standard care with or without the addition of dexamethasone. The subgroup that received corticosteroids demonstrated a lower mortality rate after a 28-day period compared to the usual care group, with the results being most notable in patients that needed mechanical ventilation or oxygen support. These results, although preliminary, imply that corticosteroids and more specifically dexamethasone can be beneficial in critically ill patients. Unless proved otherwise, we can believe that asthmatics follow the same rule and can be benefited by the use of oral corticosteroids in the setting of severe illness by COVID-19 (26). Current guidelines from experts and major respiratory societies such as GINA don’t recognize a particular danger from continuing ICS or OCS as controller treatment and underline the importance of maintaining patients in the lowest possible oral corticosteroid daily dose (25). Moreover, they strongly advise against the discontinuation of any medication without consulting a healthcare provider. It should be stressed that in a pandemic situation many patients can abruptly stop their treatment due to misinformation from the media or the Web and doctors should be prepared to reassure those patients.