Van Breedam W.,Ghent University |
Pohlmann S.,Infection Biology Unit |
Favoreel H.W.,Ghent University |
de Groot R.J.,University Utrecht |
Nauwynck H.J.,Ghent University
FEMS Microbiology Reviews | Year: 2014
Glycans are carbohydrate modifications typically found on proteins or lipids, and can act as ligands for glycan-binding proteins called lectins. Glycans and lectins play crucial roles in the function of cells and organs, and in the immune system of animals and humans. Viral pathogens use glycans and lectins that are encoded by their own or the host genome for their replication and spread. Recent advances in glycobiological research indicate that glycans and lectins mediate key interactions at the virus-host interface, controlling viral spread and/or activation of the immune system. This review reflects on glycan-lectin interactions in the context of viral infection and antiviral immunity. A short introduction illustrates the nature of glycans and lectins, and conveys the basic principles of their interactions. Subsequently, examples are discussed highlighting specific glycan-lectin interactions and how they affect the progress of viral infections, either benefiting the host or the virus. Moreover, glycan and lectin variability and their potential biological consequences are discussed. Finally, the review outlines how recent advances in the glycan-lectin field might be transformed into promising new approaches to antiviral therapy. © 2013 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.
Hofmann H.,Infection Biology Unit |
Pohlmann S.,Infection Biology Unit
Cell Host and Microbe | Year: 2011
Lozach and colleagues show that phleboviruses (bunyaviridae), which comprise important emerging viral pathogens, exploit the C-type lectin DC-SIGN for dendritic cell binding, entry, and infection. The authors elegantly visualize the cellular processes underlying DC-SIGN-dependent viral capture and uptake. © 2011 Elsevier Inc.
Hatesuer B.,Helmholtz Center for Infection Research |
Hatesuer B.,University of Tennessee Health Science Center |
Bertram S.,Infection Biology Unit |
Mehnert N.,Helmholtz Center for Infection Research |
And 7 more authors.
PLoS Pathogens | Year: 2013
Annual influenza epidemics and occasional pandemics pose a severe threat to human health. Host cell factors required for viral spread but not for cellular survival are attractive targets for novel approaches to antiviral intervention. The cleavage activation of the influenza virus hemagglutinin (HA) by host cell proteases is essential for viral infectivity. However, it is unknown which proteases activate influenza viruses in mammals. Several candidates have been identified in cell culture studies, leading to the concept that influenza viruses can employ multiple enzymes to ensure their cleavage activation in the host. Here, we show that deletion of a single HA-activating protease gene, Tmprss2, in mice inhibits spread of mono-basic H1N1 influenza viruses, including the pandemic 2009 swine influenza virus. Lung pathology was strongly reduced and mutant mice were protected from weight loss, death and impairment of lung function. Also, after infection with mono-basic H3N2 influenza A virus body weight loss and survival was less severe in Tmprss2 mutant compared to wild type mice. As expected, Tmprss2-deficient mice were not protected from viral spread and pathology after infection with multi-basic H7N7 influenza A virus. In conclusion, these results identify TMPRSS2 as a host cell factor essential for viral spread and pathogenesis of mono-basic H1N1 and H3N2 influenza A viruses. © 2013 Hateuser et al.
Kuhl A.,Hannover Medical School |
Pohlmann S.,German Primate Research Center |
Pohlmann S.,Infection Biology Unit
Zoonoses and Public Health | Year: 2012
Zoonotic transmission of Ebola virus (EBOV) to humans causes a severe haemorrhagic fever in afflicted individuals with high case-fatality rates. Neither vaccines nor therapeutics are at present available to combat EBOV infection, making the virus a potential threat to public health. To devise antiviral strategies, it is important to understand which components of the immune system could be effective against EBOV infection. The interferon (IFN) system constitutes a key innate defence against viral infections and prevents development of lethal disease in mice infected with EBOV strains not adapted to this host. Recent research revealed that expression of the host cell IFN-inducible transmembrane proteins 1-3 (IFITM1-3) and tetherin is induced by IFN and restricts EBOV infection, at least in cell culture model systems. IFITMs, tetherin and other effector molecules of the IFN system could thus pose a potent barrier against EBOV spread in humans. However, EBOV interferes with signalling events required for human cells to express these proteins. Here, we will review the strategies employed by EBOV to fight the IFN system, and we will discuss how IFITM proteins and tetherin inhibit EBOV infection. © 2012 Blackwell Verlag GmbH.
Wrensch F.,Infection Biology Unit |
Winkler M.,Infection Biology Unit |
Pohlmann S.,Infection Biology Unit
Viruses | Year: 2014
The interferon-inducible transmembrane (IFITM) proteins 1, 2 and 3 inhibit the host cell entry of several enveloped viruses, potentially by promoting the accumulation of cholesterol in endosomal compartments. IFITM3 is essential for control of influenza virus infection in mice and humans. In contrast, the role of IFITM proteins in coronavirus infection is less well defined. Employing a retroviral vector system for analysis of coronavirus entry, we investigated the susceptibility of human-adapted and emerging coronaviruses to inhibition by IFITM proteins. We found that entry of the recently emerged Middle East respiratory syndrome coronavirus (MERS-CoV) is sensitive to inhibition by IFITM proteins. In 293T cells, IFITM-mediated inhibition of cellular entry of the emerging MERS-and SARS-CoV was less efficient than blockade of entry of the globally circulating human coronaviruses 229E and NL63. Similar differences were not observed in A549 cells, suggesting that cellular context and/or IFITM expression levels can impact inhibition efficiency. The differential IFITM-sensitivity of coronaviruses observed in 293T cells afforded the opportunity to investigate whether efficiency of entry inhibition by IFITMs and endosomal cholesterol accumulation correlate. No such correlation was observed. Furthermore, entry mediated by the influenza virus hemagglutinin was robustly inhibited by IFITM3 but was insensitive to accumulation of endosomal cholesterol, indicating that modulation of cholesterol synthesis/transport did not account for the antiviral activity of IFITM3. Collectively, these results show that the emerging MERS-CoV is a target of the antiviral activity of IFITM proteins and demonstrate that mechanisms other than accumulation of endosomal cholesterol can contribute to viral entry inhibition by IFITMs. © 2014 by the authors; licensee MDPI, Basel, Switzerland.