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  • Morwitzer, M. Jane  (2)
  • Reid, St Patrick  (2)
  • 1
    In: Alcoholism: Clinical and Experimental Research, Wiley, Vol. 47, No. 1 ( 2023-01), p. 95-103
    Abstract: Over 43% of the world's population regularly consumes alcohol. Although not commonly known, alcohol can have a significant impact on the respiratory environment. Living in the time of the COVID‐19 pandemic, alcohol misuse can have a particularly deleterious effect on SARS‐CoV‐2‐infected individuals and, in turn, the overall healthcare system. Patients with alcohol use disorders have higher odds of COVID‐19‐associated hospitalization and mortality. Even though the detrimental role of alcohol on COVID‐19 outcomes has been established, the underlying mechanisms are yet to be fully understood. Alcohol misuse has been shown to induce oxidative damage in the lungs through the production of reactive aldehydes such as malondialdehyde and acetaldehyde (MAA). MAA can then form adducts with proteins, altering their structure and function. One such protein is surfactant protein D (SPD), which plays an important role in innate immunity against pathogens. Methods and Results In this study, we examined whether MAA adduction of SPD (SPD‐MAA) attenuates the ability of SPD to bind SARS‐CoV‐2 spike protein, reversing SPD‐mediated virus neutralization. Using ELISA, we show that SPD‐MAA is unable to competitively bind spike protein and prevent ACE2 receptor binding. Similarly, SPD‐MAA fails to inhibit entry of wild‐type SARS‐CoV‐2 virus into Calu‐3 cells, a lung epithelial cell line, as well as ciliated primary human bronchial epithelial cells isolated from healthy individuals. Conclusions Overall, MAA adduction of SPD, a consequence of alcohol overconsumption, represents one mechanism of compromised lung innate defense against SARS‐CoV‐2, highlighting a possible mechanism underlying COVID‐19 severity and related mortality in patients who misuse alcohol.
    Type of Medium: Online Resource
    ISSN: 0145-6008 , 1530-0277
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2046886-6
    detail.hit.zdb_id: 3167872-5
    SSG: 15,3
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  • 2
    In: Viruses, MDPI AG, Vol. 11, No. 4 ( 2019-04-23), p. 372-
    Abstract: Ebola virus (EBOV) is a filovirus that has become a global public health threat in recent years. EBOV is the causative agent of a severe, often fatal hemorrhagic fever. A productive viral infection relies on the successful recruitment of host factors for various stages of the viral life cycle. To date, several investigations have discovered specific host-pathogen interactions for various EBOV proteins. However, relatively little is known about the EBOV nucleoprotein (NP) with regard to host interactions. In the present study, we aimed to elucidate NP-host protein-protein interactions (PPIs). Affinity purification-mass spectrometry (AP-MS) was used to identify candidate NP cellular interactors. Candidate interactors RUVBL1 and RUVBL2, partner proteins belonging to the AAA+ (ATPases Associated with various cellular Activities) superfamily, were confirmed to interact with NP in co-immunoprecipitation (co-IP) and immunofluorescence (IF) experiments. Functional studies using a minigenome system revealed that the siRNA-mediated knockdown of RUVBL1 but not RUVBL2 moderately decreased EBOV minigenome activity. Super resolution structured illumination microscopy (SIM) was used to identify an association between NP and components of the R2TP complex, which includes RUVBL1, RUVBL2, RPAP3, and PIH1D1, suggesting a potential role for the R2TP complex in capsid formation. Moreover, the siRNA-mediated knockdown of RPAP3 and subsequent downregulation of PIH1D1 was shown to have no effect on minigenome activity, further suggesting a role in capsid formation. Overall, we identify RUVBL1 and RUVBL2 as novel interactors of EBOV NP and for the first time report EBOV NP recruitment of the R2TP complex, which may provide novel targets for broad-acting anti-EBOV therapeutics.
    Type of Medium: Online Resource
    ISSN: 1999-4915
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
    detail.hit.zdb_id: 2516098-9
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