scholarly journals Bioinformatics approach reveals the gene targets of Ebola virus microRNAs involved in the human skin microbiome

2017 ◽  
Author(s):  
Pei-Chun Hsu ◽  
Bin-Hao Chiou ◽  
Chun-Ming Huang
Keyword(s):  
Endothelial Cell ◽  
Ebola Virus ◽  
Propionibacterium Acnes ◽  
Immune Escape ◽  
Rna Virus ◽  
Normal Skin ◽  
Hemorrhagic Fever ◽  
Cell Swelling ◽  
Skin Microbiome ◽  
Rna Sequences

The Ebola virus, a negative-sense single-stranded RNA virus, causes severe viral hemorrhagic fever and is highly lethal. Histopathology and immunopathologic study of Ebola virus have revealed that histopathologic changes in skin tissue were mainly various degrees of endothelial cell swelling and necrosis. The interactions of microbes within or on a host are a crucial aspect of the skin immune shield. The discovery of microRNAs in Ebola virus implies that immune escape, endothelial cell rupture and tissue dissolution during Ebola virus infection are all results of the action of Ebola virus miRNAs. Keratinocytes obtained from normal skin and subsequently attached and spread on the thrombospondin protein family may play a role in initiating cell-mediated immune responses in the skin. Several miRNAs have been observed to bind the 3' untranslated region of the thrombospondin mRNA, thereby controlling its stability and translational activity. In this study, we first discover short RNA sequences that might act as miRNAs from Propionibacterium acnes by design a practical workflow of bioinformatics methods. Subsequently, we deciphered the common target gene. These RNA sequences tend to binding to the same thrombospondin protein. These RNA sequences tend to bind to the same protein , THSD4, emphasizing the potential importance of the synergistic binding of miRNAs from Ebola virus, Propionibacterium acnes , and humans to the target. By RNA expression validation, we prove the potential synergistic binding of the miRNA from Ebola virus, Propionibacterium acnes and human to the target.

scholarly journals Bioinformatics approach reveals the gene targets of Ebola virus microRNAs involved in the human skin microbiome

2017 ◽  
Author(s):  
Pei-Chun Hsu ◽  
Bin-Hao Chiou ◽  
Chun-Ming Huang
Keyword(s):  
Endothelial Cell ◽  
Ebola Virus ◽  
Propionibacterium Acnes ◽  
Immune Escape ◽  
Rna Virus ◽  
Normal Skin ◽  
Hemorrhagic Fever ◽  
Cell Swelling ◽  
Skin Microbiome ◽  
Rna Sequences

The Ebola virus, a negative-sense single-stranded RNA virus, causes severe viral hemorrhagic fever and is highly lethal. Histopathology and immunopathologic study of Ebola virus have revealed that histopathologic changes in skin tissue were mainly various degrees of endothelial cell swelling and necrosis. The interactions of microbes within or on a host are a crucial aspect of the skin immune shield. The discovery of microRNAs in Ebola virus implies that immune escape, endothelial cell rupture and tissue dissolution during Ebola virus infection are all results of the action of Ebola virus miRNAs. Keratinocytes obtained from normal skin and subsequently attached and spread on the thrombospondin protein family may play a role in initiating cell-mediated immune responses in the skin. Several miRNAs have been observed to bind the 3' untranslated region of the thrombospondin mRNA, thereby controlling its stability and translational activity. In this study, we first discover short RNA sequences that might act as miRNAs from Propionibacterium acnes by design a practical workflow of bioinformatics methods. Subsequently, we deciphered the common target gene. These RNA sequences tend to binding to the same thrombospondin protein. These RNA sequences tend to bind to the same protein , THSD4, emphasizing the potential importance of the synergistic binding of miRNAs from Ebola virus, Propionibacterium acnes , and humans to the target. By RNA expression validation, we prove the potential synergistic binding of the miRNA from Ebola virus, Propionibacterium acnes and human to the target.

scholarly journals On revealing the gene targets of Ebola virus microRNAs involved in the human skin microbiome

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e4138 ◽  
Author(s):  
Pei-Chun Hsu ◽  
Bin-Hao Chiou ◽  
Chun-Ming Huang
Keyword(s):  
Endothelial Cell ◽  
Virus Infection ◽  
Molecular Mechanisms ◽  
Ebola Virus ◽  
Propionibacterium Acnes ◽  
Immune Escape ◽  
Cell Swelling ◽  
Skin Microbiome ◽  
Rna Sequences ◽  
Ebola Virus Infection

Ebola virus, a negative-sense single-stranded RNA virus, causes severe viral hemorrhagic fever and has a high mortality rate. Histopathological and immunopathological analyses of Ebola virus have revealed that histopathological changes in skin tissue are associated with various degrees of endothelial cell swelling and necrosis. The interactions of microbes within or on a host are a crucial for the skin immune shield. The discovery of microRNAs (miRNAs) in Ebola virus implies that immune escape, endothelial cell rupture, and tissue dissolution during Ebola virus infection are a result of the effects of Ebola virus miRNAs. Keratinocytes obtained from normal skin can attach and spread through expression of the thrombospondin family of proteins, playing a role in initiation of cell-mediated immune responses in the skin. Several miRNAs have been shown to bind the 3′ untranslated region of thrombospondin mRNA, thereby controlling its stability and translational activity. In this study, we discovered short RNA sequences that may act as miRNAs from Propionibacterium acnes using a practical workflow of bioinformatics methods. Subsequently, we deciphered the common target gene. These RNA sequences tended to bind to the same thrombospondin protein, THSD4, emphasizing the potential importance of the synergistic binding of miRNAs from Ebola virus, Propionibacterium acnes, and humans to the target. These results provide important insights into the molecular mechanisms of thrombospondin proteins and miRNAs in Ebola virus infection.

scholarly journals Structure of the Ebola virus envelope protein MPER/TM domain and its interaction with the fusion loop explains their fusion activity

2017 ◽  
Vol 114 (38) ◽  
pp. E7987-E7996 ◽  
Author(s):  
Jinwoo Lee ◽  
David A. Nyenhuis ◽  
Elizabeth A. Nelson ◽  
David S. Cafiso ◽  
Judith M. White ◽  
...  
Keyword(s):  
Membrane Fusion ◽  
Viral Entry ◽  
Ebola Virus ◽  
Rna Virus ◽  
Hemorrhagic Fever ◽  
Virus Envelope ◽  
Tm Domain ◽  
Virus Envelope Protein ◽  
Niemann Pick ◽  
Fusion Loop

Ebolavirus (EBOV), an enveloped filamentous RNA virus causing severe hemorrhagic fever, enters cells by macropinocytosis and membrane fusion in a late endosomal compartment. Fusion is mediated by the EBOV envelope glycoprotein GP, which consists of subunits GP1 and GP2. GP1 binds to cellular receptors, including Niemann-Pick C1 (NPC1) protein, and GP2 is responsible for low pH-induced membrane fusion. Proteolytic cleavage and NPC1 binding at endosomal pH lead to conformational rearrangements of GP2 that include exposing the hydrophobic fusion loop (FL) for insertion into the cellular target membrane and forming a six-helix bundle structure. Although major portions of the GP2 structure have been solved in pre- and postfusion states and although current models place the transmembrane (TM) and FL domains of GP2 in close proximity at critical steps of membrane fusion, their structures in membrane environments, and especially interactions between them, have not yet been characterized. Here, we present the structure of the membrane proximal external region (MPER) connected to the TM domain: i.e., the missing parts of the EBOV GP2 structure. The structure, solved by solution NMR and EPR spectroscopy in membrane-mimetic environments, consists of a helix-turn-helix architecture that is independent of pH. Moreover, the MPER region is shown to interact in the membrane interface with the previously determined structure of the EBOV FL through several critical aromatic residues. Mutation of aromatic and neighboring residues in both binding partners decreases fusion and viral entry, highlighting the functional importance of the MPER/TM–FL interaction in EBOV entry and fusion.

scholarly journals Ebola Virus ? A Global Threat

2015 ◽  
Vol 5 (1) ◽  
pp. 44-51
Author(s):  
Mejbah Uddin Ahmed ◽  
Sushmita Roy
Keyword(s):  
Nonhuman Primates ◽  
Ebola Virus ◽  
Rna Virus ◽  
Close Contact ◽  
Multiorgan Failure ◽  
Hemorrhagic Fever ◽  
Human Infection ◽  
Current Data ◽  
Sub Saharan Africa ◽  
Virus Infections

Ebola virus is a filamentous, enveloped, non-segmented, single-stranded, negative-sense RNA virus. It belongs to the Filoviridae and was first recognized near the Ebola River valley in Zaire in 1976. Since then most of the outbreaks have occurred to both human and nonhuman primates in sub-Saharan Africa. Ebola virus causes highly fatal hemorrhagic fever in human and nonhuman primates. In addition to hemorrhagic fever, it could be used as a bioterrorism agent. Although its natural reservoir is yet to be proven, current data suggest that fruit bats are the possibility. Infection has also been documented through the handling of infected chimpanzees, gorillas, monkeys, forest antelope and porcupines. Human infection is caused through close contact with the blood, secretion, organ or other body fluids of infected animal. Human-to-human transmission is also possible. Ebola virus infections are characterized by immune suppression and a systemic inflammatory response that causes impairment of the vascular, coagulation, and immune systems, leading to multiorgan failure and shock. The virus constitutes an important public health threat in Africa and also worldwide as no effective treatment or vaccine is available till now DOI: http://dx.doi.org/10.3329/jemc.v5i1.21497 J Enam Med Col 2015; 5(1): 44-51

scholarly journals Ebola Virus Glycoprotein Toxicity Is Mediated by a Dynamin-Dependent Protein-Trafficking Pathway

2005 ◽  
Vol 79 (1) ◽  
pp. 547-553 ◽  
Author(s):  
Nancy J. Sullivan ◽  
Mary Peterson ◽  
Zhi-yong Yang ◽  
Wing-pui Kong ◽  
Heinricus Duckers ◽  
...  
Keyword(s):  
Cell Surface ◽  
Ebola Virus ◽  
Immune Escape ◽  
Cell Damage ◽  
Hemorrhagic Fever ◽  
Viral Envelope ◽  
Cellular Damage ◽  
Cell Surface Expression

ABSTRACT Ebola virus infection causes a highly lethal hemorrhagic fever syndrome associated with profound immunosuppression through its ability to induce widespread inflammation and cellular damage. Though GP, the viral envelope glycoprotein, mediates many of these effects, the molecular events that underlie Ebola virus cytopathicity are poorly understood. Here, we define a cellular mechanism responsible for Ebola virus GP cytotoxicity. GP selectively decreased the expression of cell surface molecules that are essential for cell adhesion and immune function. GP dramatically reduced levels of αVβ3 without affecting the levels of α2β1 or cadherin, leading to cell detachment and death. This effect was inhibited in vitro and in vivo by brefeldin A and was dependent on dynamin, the GTPase. GP also decreased cell surface expression of major histocompatibility complex class I molecules, which alters recognition by immune cells, and this effect was also dependent on the mucin domain previously implicated in GP cytotoxicity. By altering the trafficking of select cellular proteins, Ebola virus GP inflicts cell damage and may facilitate immune escape by the virus.

scholarly journals Identification and characterization of defective viral genomes in Ebola virus infected rhesus macaques

2021 ◽  
Author(s):  
Rebecca I. Johnson ◽  
Beata Boczkowska ◽  
Kendra Alfson ◽  
Taylor Weary ◽  
Heather Menzie ◽  
...  
Keyword(s):  
Nonhuman Primates ◽  
Ebola Virus ◽  
Sequence Data ◽  
Rna Virus ◽  
Hemorrhagic Fever ◽  
Marburg Virus ◽  
Immunostimulatory Activity ◽  
Viral Genomes

Ebola virus (EBOV), of the family Filoviridae, is an RNA virus that can cause hemorrhagic fever with a high mortality rate. Defective viral genomes (DVGs) are truncated genomes that have been observed during multiple RNA virus infections, including  in vitro EBOV infection, and have previously been associated with viral persistence and immunostimulatory activity. As DVGs have been detected in cells persistently infected with EBOV, we hypothesized that DVGs may also accumulate during viral replication in filovirus-infected hosts. Therefore, we interrogated sequence data from serum and tissues using a bioinformatics tool in order to identify the presence of DVGs in nonhuman primates (NHPs) infected with EBOV, Sudan virus (SUDV) or Marburg virus (MARV). Multiple 5’ copy-back DVGs (cbDVGs) were detected in NHP serum during the acute phase of filovirus infection. While the relative abundance of total DVGs in most animals was low, serum collected during acute EBOV and SUDV infections, but not MARV infection, contained a higher proportion of short trailer sequence cbDVGs than the challenge stock. This indicated an accumulation of these DVGs throughout infection, potentially due to the preferential replication of short DVGs over the longer viral genome. Using RT-PCR and deep sequencing, we also confirmed the presence of 5’ cbDVGs in EBOV-infected NHP testes, which is of interest due to EBOV persistence in semen of male survivors of infection. This work suggests that DVGs play a role in EBOV infection in vivo and further study will lead to a better understanding of EBOV pathogenesis. Importance The study of filovirus pathogenesis is critical for understanding the consequences of infection and the development of strategies to ameliorate future outbreaks. Defective viral genomes (DVGs) have been detected during EBOV infections in vitro , however their presence in in vivo infections remains unknown. In this study, DVGs were detected in samples collected from EBOV- and SUDV-infected nonhuman primates (NHPs). The accumulation of these DVGs in the trailer region of the genome during infection indicates a potential role in EBOV and SUDV pathogenesis. In particular, the presence of DVGs in the testes of infected NHPs requires further investigation as it may be linked to the establishment of persistence.

scholarly journals Porcine Reproductive and Respiratory Syndrome Virus: Immune Escape and Application of Reverse Genetics in Attenuated Live Vaccine Development

Vaccines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 480
Author(s):  
Honglei Wang ◽  
Yangyang Xu ◽  
Wenhai Feng
Keyword(s):  
Immune Responses ◽  
Reverse Genetics ◽  
Vaccine Development ◽  
Immune Escape ◽  
Rna Virus ◽  
Economic Losses ◽  
Respiratory Syndrome Virus ◽  
Live Vaccines ◽  
Host Immune Responses ◽  
Inactivated Vaccines

Porcine reproductive and respiratory syndrome virus (PRRSV), an RNA virus widely prevalent in pigs, results in significant economic losses worldwide. PRRSV can escape from the host immune response in several processes. Vaccines, including modified live vaccines and inactivated vaccines, are the best available countermeasures against PRRSV infection. However, challenges still exist as the vaccines are not able to induce broad protection. The reason lies in several facts, mainly the variability of PRRSV and the complexity of the interaction between PRRSV and host immune responses, and overcoming these obstacles will require more exploration. Many novel strategies have been proposed to construct more effective vaccines against this evolving and smart virus. In this review, we will describe the mechanisms of how PRRSV induces weak and delayed immune responses, the current vaccines of PRRSV, and the strategies to develop modified live vaccines using reverse genetics systems.

scholarly journals The Function of the PRRSV–Host Interactions and Their Effects on Viral Replication and Propagation in Antiviral Strategies

Vaccines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 364
Author(s):  
Jun Ma ◽  
Lulu Ma ◽  
Meiting Yang ◽  
Wei Wu ◽  
Wenhai Feng ◽  
...  
Keyword(s):  
Immune Response ◽  
Molecular Mechanisms ◽  
Immune Escape ◽  
Rna Virus ◽  
Economic Losses ◽  
Respiratory Syndrome Virus ◽  
Swine Industry ◽  
Live Virus ◽  
Virus Challenge ◽  
Host Interactions

Porcine reproductive and respiratory syndrome virus (PRRSV) affects the global swine industry and causes disastrous economic losses each year. The genome of PRRSV is an enveloped single-stranded positive-sense RNA of approximately 15 kb. The PRRSV replicates primarily in alveolar macrophages of pig lungs and lymphatic organs and causes reproductive problems in sows and respiratory symptoms in piglets. To date, studies on how PRRSV survives in the host, the host immune response against viral infections, and pathogenesis, have been reported. PRRSV vaccines have been developed, including inactive virus, modified live virus, attenuated live vaccine, DNA vaccine, and immune adjuvant vaccines. However, there are certain problems with the durability and effectiveness of the licensed vaccines. Moreover, the high variability and fast-evolving populations of this RNA virus challenge the design of PRRSV vaccines, and thus effective vaccines against PRRSV have not been developed successfully. As is well known, viruses interact with the host to escape the host’s immune response and then replicate and propagate in the host, which is the key to virus survival. Here, we review the complex network and the mechanism of PRRSV–host interactions in the processes of virus infection. It is critical to develop novel antiviral strategies against PRRSV by studying these host–virus interactions and structures to better understand the molecular mechanisms of PRRSV immune escape.

scholarly journals Equine-Origin Immunoglobulin Fragments Protect Nonhuman Primates from Ebola Virus Disease

2018 ◽  
Vol 93 (5) ◽  
Author(s):  
Hualei Wang ◽  
Gary Wong ◽  
Wenjun Zhu ◽  
Shihua He ◽  
Yongkun Zhao ◽  
...  
Keyword(s):  
Large Scale ◽  
Nonhuman Primates ◽  
Ebola Virus ◽  
Virus Disease ◽  
Hemorrhagic Fever ◽  
West African ◽  
Clinical Testing ◽  
The Past ◽  
Over 40 Years

ABSTRACT Ebola virus (EBOV) infections result in aggressive hemorrhagic fever in humans, with fatality rates reaching 90% and with no licensed specific therapeutics to treat ill patients. Advances over the past 5 years have firmly established monoclonal antibody (MAb)-based products as the most promising therapeutics for treating EBOV infections, but production is costly and quantities are limited; therefore, MAbs are not the best candidates for mass use in the case of an epidemic. To address this need, we generated EBOV-specific polyclonal F(ab′)2 fragments from horses hyperimmunized with an EBOV vaccine. The F(ab′)2 was found to potently neutralize West African and Central African EBOV in vitro. Treatment of nonhuman primates (NHPs) with seven doses of 100 mg/kg F(ab′)2 beginning 3 or 5 days postinfection (dpi) resulted in a 100% survival rate. Notably, NHPs for which treatment was initiated at 5 dpi were already highly viremic, with observable signs of EBOV disease, which demonstrated that F(ab′)2 was still effective as a therapeutic agent even in symptomatic subjects. These results show that F(ab′)2 should be advanced for clinical testing in preparation for future EBOV outbreaks and epidemics. IMPORTANCE EBOV is one of the deadliest viruses to humans. It has been over 40 years since EBOV was first reported, but no cure is available. Research breakthroughs over the past 5 years have shown that MAbs constitute an effective therapy for EBOV infections. However, MAbs are expensive and difficult to produce in large amounts and therefore may only play a limited role during an epidemic. A cheaper alternative is required, especially since EBOV is endemic in several third world countries with limited medical resources. Here, we used a standard protocol to produce large amounts of antiserum F(ab′)2 fragments from horses vaccinated with an EBOV vaccine, and we tested the protectiveness in monkeys. We showed that F(ab′)2 was effective in 100% of monkeys even after the animals were visibly ill with EBOV disease. Thus, F(ab′)2 could be a very good option for large-scale treatments of patients and should be advanced to clinical testing.

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