Sequential events in the morphogenesis of Japanese encephalitis virus

Leary, Kathryn; Blair, Carol D.

doi:10.1016/s0022-5320(80)90050-7

Cited by 72 publications

(63 citation statements)

References 16 publications

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“…In medulloblasts and glioblasts, we observed similar structural abnormalities formed by membrane modifications such as the formation of SMS, ER proliferation, accumulation and convolution of membranes, which are in accordance with typical cell abnormalities described for other flavivirus infections (Matsumura et al, 1971;Ko et al, 1979;Leary & Blair, 1980;Ho et al, 1987;Ng & Hong, 1989;Chu & Westaway, 1992;Ng et al, 1994b). SMS is a typical flavivirus-induced structure associated with RER (Hase, 1993; Wang et al, 1997) that is probably formed through budding from the RER.…”

Section: Discussionsupporting

confidence: 89%

“…Either cis or trans modes of maturation have been shown in several flaviviruses (e.g. WNV, DENV-2 and TBEV), depending on the particular virus strain and cells used (Leary & Blair, 1980;Hase et al, 1987;Ng, 1987;Ng & Hong, 1989;Ng et al, 1994aNg et al, , 2001Mackenzie et al, 1999; Šenigl et al, 2006). Šenigl et al (2006) described that TBEV exhibits a trans mode of maturation in mammalian cells, but a cis mode in tick cells.…”

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confidence: 99%

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Morphological changes in human neural cells following tick-borne encephalitis virus infection

Růžek

Vancová

Tesařová

et al. 2009

Journal of General Virology

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Tick-borne encephalitis (TBE) is one of the leading and most dangerous human viral neuroinfections in Europe and north-eastern Asia. The clinical manifestations include asymptomatic infections, fevers and debilitating encephalitis that might progress into chronic disease or fatal infection. To understand TBE pathology further in host nervous systems, three human neural cell lines, neuroblastoma, medulloblastoma and glioblastoma, were infected with TBE virus (TBEV). The susceptibility and virus-mediated cytopathic effect, including ultrastructural and apoptotic changes of the cells, were examined. All the neural cell lines tested were susceptible to TBEV infection. Interestingly, the neural cells produced about 100-to 10 000-fold higher virus titres than the conventional cell lines of extraneural origin, indicating the highly susceptible nature of neural cells to TBEV infection. The infection of medulloblastoma and glioblastoma cells was associated with a number of major morphological changes, including proliferation of membranes of the rough endoplasmic reticulum and extensive rearrangement of cytoskeletal structures. The TBEV-infected cells exhibited either necrotic or apoptotic morphological features. We observed ultrastructural apoptotic signs (condensation, margination and fragmentation of chromatin) and other alterations, such as vacuolation of the cytoplasm, dilatation of the endoplasmic reticulum cisternae and shrinkage of cells, accompanied by a high density of the cytoplasm. On the other hand, infected neuroblastoma cells did not exhibit proliferation of membranous structures. The virions were present in both the endoplasmic reticulum and the cytoplasm. Cells were dying preferentially by necrotic mechanisms rather than apoptosis. The neuropathological significance of these observations is discussed. INTRODUCTIONTick-borne encephalitis virus (TBEV) is the most medically important member of the tick-borne group of the genus Flavivirus within the family Flaviviridae (Thiel et al., 2005). The virus represents a causative agent of tick-borne encephalitis (TBE), a severe infection of the central nervous system (CNS) (Gritsun et al., 2003), which is prevalent throughout wide areas in Europe and Asia.The nature of the host cell response to TBEV infection remains undefined. Characteristic, but not disease-specific neuropathologic changes in the CNS include meningitis and polioencephalomyelitis predominantly in the spinal cord, brainstem and cerrebellum associated with inflammatory cell infiltration. These pathological changes have been described in mice (Osetowska & Wró blewskaMularczyk, 1966; Rů žek et al., 2009), hamsters (Simon et al., 1966), monkeys (Simon et al., 1967 and humans (Seitelberger & Jellinger, 1966; Környey, 1978;Beer et al., 1999; Schellinger et al., 2000; Gelpi et al., 2005 Gelpi et al., , 2006. Although cytopathic effects (CPEs) have been observed primarily in virus-infected neurons, other cells can also exhibit pathological changes, presumably through bystander injury.To clarify the inter...

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Section: Discussionsupporting

confidence: 89%

mentioning

confidence: 99%

Morphological changes in human neural cells following tick-borne encephalitis virus infection

Růžek

Vancová

Tesařová

et al. 2009

Journal of General Virology

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“…This virus induces membrane structures called convoluted membranes and paracrystalline structures, representing the putative sites of viral polyprotein processing. In addition, proliferating ER and vesicles of about 100 nm in diameter described as small, spherical smooth membrane structures that seem to harbor the viral RCs were observed (9,29,(43)(44)(45)(46). It is possible that the cytoplasmic foci observed in our DV studies represent one or several of these membrane structures.…”

Section: Discussionmentioning

confidence: 99%

Subcellular Localization and Membrane Topology of the Dengue Virus Type 2 Non-structural Protein 4B

Miller

Sparacio

Bartenschlager

2006

Journal of Biological Chemistry

253

289

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Dengue virus (DV) is a member of the family Flaviviridae. These positive strand RNA viruses encode a polyprotein that is processed in case of DV into 10 proteins. Although for most of these proteins distinct functions have been defined, this is less clear for the highly hydrophobic non-structural protein (NS) 4B. Despite its possible role as an antagonist of the interferon-induced antiviral response, this protein may play an additional more direct role for viral replication. In this study we determined the subcellular localization, membrane association, and membrane topology of DV NS4B. We found that NS4B resides primarily in cytoplasmic foci originating from the endoplasmic reticulum. NS4B colocalizes with NS3 and double-stranded RNA, an intermediate of viral replication, arguing that NS4B is part of the membrane-bound viral replication complex. Biochemical analysis revealed that NS4B is an integral membrane protein, and that its preceding 2K signal sequence is not required for this integration. We identified three membrane-spanning segments in the COOH-terminal part of NS4B that are sufficient to target a cytosolic marker protein to intracellular membranes. Furthermore, we established a membrane topology model of NS4B in which the NH 2 -terminal part of the protein is localized in the endoplasmic reticulum lumen, whereas the COOH-terminal part is composed of three trans-membrane domains with the COOH-terminal tail localized in the cytoplasm. This topology model provides a good starting point for a detailed investigation of the function of NS4B in the DV life cycle. The mosquito-transmitted Dengue virus (DV)3 is the causative agent of dengue fever, the most prevalent arthropod-borne viral illness in humans with 50 -100 million individuals infected annually worldwide (1). Dengue fever is characterized by high fever, chills, body aches, and skin rash and ranges from mild, flu-like symptoms to severe forms, which are dengue hemorrhagic fever and the dengue shock syndrome. The four serotypes of DV identified so far (DV1-4) belong to the genus Flavivirus in the family Flaviviridae. Flaviviruses are small, enveloped viruses that have a single-stranded genomic RNA of positive polarity ϳ11 kb in length. This RNA serves as mRNA for translation of a large polyprotein (3,391 amino acids in case of DV2) at the rough endoplasmic reticulum. The viral polyprotein is co-and post-translationally processed into three structural proteins (C, prM, and E) and seven nonstructural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5). The amino termini of prM, E, NS1, and NS4B are generated upon cleavage by the host signal peptidase in the lumen of the ER, whereas processing of most of the other NS proteins and the COOH terminus of the C protein is carried out by the viral two-component protease NS2B-3 in the cytoplasm of DV-infected cells (2-4). For cleavage of the COOH terminus of NS1 an unknown ER resident protease seems to be responsible (5). A Golgi-localized furin protease mediates cleavage of prM at a late state of infection to...

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“…No direct evidence for envelopment of flaviviruses by an intracellular budding process has been obtained by either thin-section or freeze-fracture studies of infected cells (Murphy et ai., 1968;Demsey et a1., 1974;Westaway, 1980;Murphy, 1980). Leary and Blair (1980) have suggested that virion assembly may occur within lucent vesicles budded from cytopathic vacuoles. Intracellular virions have been observed to exit from infected cells by at least two routes.…”

Section: Viral Morphogenesismentioning

confidence: 99%

Replication of Flaviviruses

Brinton

1986

The Togaviridae and Flaviviridae

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Sequential events in the morphogenesis of Japanese encephalitis virus

Cited by 72 publications

References 16 publications

Morphological changes in human neural cells following tick-borne encephalitis virus infection

Morphological changes in human neural cells following tick-borne encephalitis virus infection

Subcellular Localization and Membrane Topology of the Dengue Virus Type 2 Non-structural Protein 4B

Replication of Flaviviruses

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