#Cytokine Effects on the Entry of #Filovirus Envelope Pseudotyped Virus-Like Particles into Primary #Human #Macrophages (Viruses, abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Viruses. 2019 Sep 23;11(10). pii: E889. doi: 10.3390/v11100889.

Cytokine Effects on the Entry of Filovirus Envelope Pseudotyped Virus-Like Particles into Primary Human Macrophages.

Stantchev TS1, Zack-Taylor A2, Mattson N3, Strebel K4, Broder CC5, Clouse KA6.

Author information: 1 Division of Biotechnology Review and Research 1 (DBRR1), Office of Biotechnology Products (OBP), Center for Drug Evaluation and Research (CDER), US Food and Drug Administration (FDA), Silver Spring, MD 20993, USA. tzanko.stantchev@fda.hhs.gov. 2 Division of Biotechnology Review and Research 1 (DBRR1), Office of Biotechnology Products (OBP), Center for Drug Evaluation and Research (CDER), US Food and Drug Administration (FDA), Silver Spring, MD 20993, USA. autumn.zack-taylor@fda.hhs.gov. 3 Division of Biotechnology Review and Research 1 (DBRR1), Office of Biotechnology Products (OBP), Center for Drug Evaluation and Research (CDER), US Food and Drug Administration (FDA), Silver Spring, MD 20993, USA. nicholas.mattson@fda.hhs.gov. 4 Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20814, USA. kstrebel@niaid.nih.gov. 5 Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences (USUHS), Bethesda, MD 20814, USA. christopher.broder@usuhs.edu. 6 Division of Biotechnology Review and Research 1 (DBRR1), Office of Biotechnology Products (OBP), Center for Drug Evaluation and Research (CDER), US Food and Drug Administration (FDA), Silver Spring, MD 20993, USA. kathleen.clouse@fda.hhs.gov.

 

Abstract

Macrophages are one of the first and also a major site of filovirus replication and, in addition, are a source of multiple cytokines, presumed to play a critical role in the pathogenesis of the viral infection. Some of these cytokines are known to induce macrophage phenotypic changes in vitro, but how macrophage polarization may affect the cell susceptibility to filovirus entry remains largely unstudied. We generated different macrophage subsets using cytokine pre-treatment and subsequently tested their ability to fuse with beta-lactamase containing virus-like particles (VLP), pseudotyped with the surface glycoprotein of Ebola virus (EBOV) or the glycoproteins of other clinically relevant filovirus species. We found that pre-incubation of primary human monocyte-derived macrophages (MDM) with interleukin-10 (IL-10) significantly enhanced filovirus entry into cells obtained from multiple healthy donors, and the IL-10 effect was preserved in the presence of pro-inflammatory cytokines found to be elevated during EBOV disease. In contrast, fusion of IL-10-treated macrophages with influenza hemagglutinin/neuraminidase pseudotyped VLPs was unchanged or slightly reduced. Importantly, our in vitro data showing enhanced virus entry are consistent with the correlation established between elevated serum IL-10 and increased mortality in filovirus infected patients and also reveal a novel mechanism that may account for the IL-10-mediated increase in filovirus pathogenicity.

KEYWORDS: Ebola virus (EBOV); cytokines; filoviruses; interleukin-10 (IL-10)

PMID: 31547585 DOI: 10.3390/v11100889

Keywords: Ebola; Filovirus; Cytokines; Immunopathology; Viral pathogenesis.

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Giuseppe Michieli

I am an Italian blogger, active since 2005 with main focus on emerging infectious diseases such as avian influenza, SARS, antibiotics resistance, and many other global Health issues. Other fields of interest are: climate change, global warming, geological and biological sciences. My activity consists mainly in collection and analysis of news, public services updates, confronting sources and making decision about what are the 'signals' of an impending crisis (an outbreak, for example). When a signal is detected, I follow traces during the entire course of an event. I started in 2005 my blog ''A TIME'S MEMORY'', now with more than 40,000 posts and 3 millions of web interactions. Subsequently I added an Italian Language blog, then discontinued because of very low traffic and interest. I contributed for seven years to a public forum (FluTrackers.com) in the midst of the Ebola epidemic in West Africa in 2014, I left the site to continue alone my data tracking job.