Crystallization and preliminary X-ray analysis of human rhinovirus serotype 2 (HRV2)

Verdaguer, N.; Marlovits, Thomas C.; Bravo, Jerónimo; Stuart, David I.; Blaas, Dieter; Fita, Ignacio

doi:10.1107/s0907444999006137

Cited by 4 publications

(2 citation statements)

References 17 publications

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“…Our HTS identified also LDLR and DNCL2B (Table 2) as cellular factors required for BDV cell entry. LDLR has been shown to function as a receptor for rhinoviruses (34,56) and potentially also HCV (16); whether LDLR can serve a similar role for BDV remains to be investigated. In addition, LDLR can trigger the clathrin-mediated endocytotic pathway (5), which we have found to direct the entry of BDV into cells (submitted for publication).…”

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Identification of Host Factors Involved in Borna Disease Virus Cell Entry through a Small Interfering RNA Functional Genetic Screen

Clemente

Sisman

Aza-Blanc

et al. 2010

J Virol

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Borna disease virus (BDV), the prototypic member of the Bornaviridae family, within the order Mononegavirales, is highly neurotropic and constitutes an important model system for the study of viral persistence in the central nervous system (CNS) and associated disorders. The virus surface glycoprotein (G) has been shown to direct BDV cell entry via receptor-mediated endocytosis, but the mechanisms governing cell tropism and propagation of BDV within the CNS are unknown. We developed a small interfering RNA (siRNA)-based screening to identify cellular genes and pathways that specifically contribute to BDV G-mediated cell entry. Our screen relied on silencing-mediated increased survival of cells infected with rVSV⌬G*/BDVG, a cytolytic recombinant vesicular stomatitis virus expressing BDV G that mimics the cell tropism and entry pathway of bona fide BDV. We identified 24 cellular genes involved in BDV G-mediated cell entry. Identified genes are known to participate in a broad range of distinct cellular functions, revealing a complex process associated with BDV cell entry. The siRNA-based screening strategy we have developed should be applicable to identify cellular genes contributing to cell entry mediated by surface G proteins of other viruses. (12,49,51). However, based on its unique genetics and biological features, BDV is considered to be the prototypic member of a new virus family, Bornaviridae, within the order Mononegavirales (13, 49). BDV is highly neurotropic and causes central nervous system (CNS) disease in a variety of vertebrate species that is frequently manifested by behavioral abnormalities (25,53). Both host and viral factors contribute to a variable period of incubation and heterogeneity in the symptoms and pathology associated with BDV infection (18,20,32,44,46). BDV provides an important model for the investigation of both immune-mediated pathological events associated with virus-induced neurological disease and mechanisms whereby viruses induce neurodevelopmental and behavioral disturbances in the absence of the hallmarks of cytolysis and inflammation (19,24,42). Borna disease virus (BDV) is an enveloped virus with a nonsegmented negative-strand (NNS) RNA genome whose organization (3Ј-N-p10/P-M-G-L-5Ј) is characteristic of mononegaviruses (MNV)Serological data and molecular epidemiological studies suggest that BDV, or a BDV-like virus, can infect humans, and it might be associated with certain neuropsychiatric disorders (23,29). Moreover, the recent identification of an avian bornavirus (22, 45) underscores the prospect of finding other BDV-like emerging viruses of potential relevance to human health. The identification of host cell factors involved in BDV cell entry will contribute to a better understanding of BDV cell tropism and propagation within the CNS, a first and necessary step to elucidate the mechanisms by which BDV disrupts normal brain functions. Likewise, the development of effective antiviral strategies to combat bornavirus infections may be facilitated by targeting host cell fact...

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