<i>In vivo</i>
            oligomerization and raft localization of Ebola virus protein VP40 during vesicular budding

Panchal, Rekha G.; Ruthel, Gordon; Kenny, Tara; Kallstrom, George; Lane, Douglas; Badie, Shirin S.; Liu, Limin; Bavari, Sina; Aman, M. Javad

doi:10.1073/pnas.2533915100

Cited by 190 publications

(238 citation statements)

References 30 publications

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“…25 VP24 and VP35 participate in viral nucleocapsid assembly, 18 and VP40 is essential for virus budding and assembly. [26][27][28] In addition, GP, VP24, VP30, VP35 and VP40 interact with multiple host proteins to complete the viral life cycle and to suppress the host immune response.…”

Section: Introductionmentioning

confidence: 99%

Predictive and comparative analysis of Ebolavirus proteins

2015

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Ebolavirus is the pathogen for Ebola Hemorrhagic Fever (EHF). This disease exhibits a high fatality rate and has recently reached a historically epidemic proportion in West Africa. Out of the 5 known Ebolavirus species, only Reston ebolavirus has lost human pathogenicity, while retaining the ability to cause EHF in long-tailed macaque. Significant efforts have been spent to determine the three-dimensional (3D) structures of Ebolavirus proteins, to study their interaction with host proteins, and to identify the functional motifs in these viral proteins. Here, in light of these experimental results, we apply computational analysis to predict the 3D structures and functional sites for Ebolavirus protein domains with unknown structure, including a zinc-finger domain of VP30, the RNA-dependent RNA polymerase catalytic domain and a methyltransferase domain of protein L. In addition, we compare sequences of proteins that interact with Ebolavirus proteins from RESTV-resistant primates with those from RESTV-susceptible monkeys. The host proteins that interact with GP and VP35 show an elevated level of sequence divergence between the RESTV-resistant and RESTV-susceptible species, suggesting that they may be responsible for host specificity. Meanwhile, we detect variable positions in protein sequences that are likely associated with the loss of human pathogenicity in RESTV, map them onto the 3D structures and compare their positions to known functional sites. VP35 and VP30 are significantly enriched in these potential pathogenicity determinants and the clustering of such positions on the surfaces of VP35 and GP suggests possible uncharacterized interaction sites with host proteins that contribute to the virulence of Ebolavirus.

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Section: Introductionmentioning

confidence: 99%

Predictive and comparative analysis of Ebolavirus proteins

2015

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“…NP, viral protein (VP)35, VP30, and L, the RNA-dependent RNA polymerase, are components of the nucleocapsid and are essential for viral replication and transcription (5). VP40 is the matrix protein and is critical for viral budding (18,19). VP24 is essential for the formation of nucleocapsids composed of NP, VP35, and viral RNA (20).…”

mentioning

confidence: 99%

Generation of biologically contained Ebola viruses

Halfmann

Kim

Ebihara

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

119

163

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Ebola virus (EBOV), a public health concern in Africa and a potential biological weapon, is classified as a biosafety level-4 agent because of its high mortality rate and the lack of approved vaccines and antivirals. Basic research into the mechanisms of EBOV pathogenicity and the development of effective countermeasures are restricted by the current biosafety classification of EBOVs. We therefore developed biologically contained EBOV that express a reporter gene instead of the VP30 gene, which encodes an essential transcription factor. A Vero cell line that stably expresses VP30 provides this essential protein in trans and biologically confines the virus to its complete replication cycle in this cell line. This complementation approach is highly efficient because biologically contained EBOVs lacking the VP30 gene grow to titers similar to those obtained with wild-type virus. Moreover, EBOVs lacking the VP30 gene are indistinguishable in their morphology from wild-type virus and are genetically stable, as determined by sequence analysis after seven serial passages in VP30-expressing Vero cells. We propose that this system provides a safe means to handle EBOV outside a biosafety level-4 facility and will stimulate critical studies on the EBOV life cycle as well as large-scale screening efforts for compounds with activity against this lethal virus.antiviral screening ͉ reverse genetics ͉ vaccine development

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“…The role of membrane rafts in the assembly and budding of enveloped viruses has been investigated for influenza virus [59,63,[150][151][152][153][154][155][156][157][158][159][160], HIV-1 [63,[161][162][163][164][165][166][167][168][169][170][171][172][173], HTLV-1 [174], measles virus (Paramyxoviridae) [63,175,176], Sendai virus [Paramyxoviridae] [177,178], Newcastle disease virus (NDV; Paramyxoviridae) [179,180], RSV [147,148,[181][182][183][184], HSV [185,186], murine cytomegalovirus (MCMV; Herpesviridae) [187], Ebola virus [70,188], Marburg virus [70], and vesicular stomatitis virus (VSV; Rhabdoviridae) …”

Section: Role Of Membrane Rafts In Virus Genome Replication Assemblymentioning

confidence: 99%

“…The cellular TSG101 protein, a component of the vacuolar protein sorting machinery, actively redirects to membrane rafts at the cell surface, along with VP40, due to VP40 binding with TSG101 through a PTAP motif. Thus, budding complexes containing VP40, TSG101, and possibly other components accumulate in membrane rafts to serve in virus budding [188].…”

Section: Role Of Membrane Rafts In Virus Genome Replication Assemblymentioning

confidence: 99%

Role of Membrane Rafts in Viral Infection

Takahashi¹,

Suzuki²

2009

TODJ

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Membrane rafts are small (10-200 nm), heterogeneous, highly dynamic, sterol-and sphingolipid-enriched domains that compartmentalize cellular processes. Many studies have established that membrane rafts play an important role in the process of virus infection cycle and virus-associated diseases. It is well known that many viral components or virus receptors are concentrated in the lipid microdomains. Viruses are divided into four main classes, nonenveloped RNA virus, enveloped RNA virus, nonenveloped DNA virus, and enveloped DNA virus. General virus infection cycle is also classified into two sections, the early stage (entry) and the late stage (assembly and budding of virion). Caveola-dependent endocytosis has been investigated mostly by analysis of cell entry of the SV40 representative of polyomaviruses. Thus, the study of membrane rafts has been partially advanced by virological researches. Membrane rafts also act as a scaffold of many cellular signal transductions. Involvement of membrane rafts in many virus-associated diseases is often responsible for up-or down-regulation of cellular signal transductions. What is the role of membrane rafts in virus replications? Viruses do not necessarily require and probably utilize membrane rafts for more efficiency in virus entry, viral genome replication, high-infective virion production, and cellular signaling activation toward advantageous virus replication. In this review, we described the involvement of membrane rafts in the virus life cycle and virus-associated diseases.

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In vivo oligomerization and raft localization of Ebola virus protein VP40 during vesicular budding

Cited by 190 publications

References 30 publications

Predictive and comparative analysis of Ebolavirus proteins

Predictive and comparative analysis of Ebolavirus proteins

Generation of biologically contained Ebola viruses

Role of Membrane Rafts in Viral Infection

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