| 1. |
- Backström, Ellenor, 1980-, et al.
(författare)
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Adenovirus L4-22K stimulates major late transcription by a mechanism requiring the intragenic late-specific transcription factor-binding site
- 2010
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Ingår i: Virus Research. - : Elsevier BV. - 0168-1702 .- 1872-7492. ; 151:2, s. 220-228
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Tidskriftsartikel (refereegranskat)abstract
- The adenovirus major late promoter (MLP) generates a primary transcript that undergoes a complex pattern of regulated alternative RNA splicing and polyadenylation events. The late-specific activation of the MLP requires binding of two infected-cell specific transcription factor complexes, DEF-A and DEF-B, to the so-called DE sequence located downstream of the MLP start site. Previous studies have shown that DEF-B is a homodimer of the viral IVa2 protein and suggested that DEF-A is a heterodimer of IVa2 and an unknown protein. Here we have searched for a possible DEF-A candidate protein. The adenovirus L4-33K protein functions as a virus-encoded alternative RNA splicing factor, stimulating cytoplasmic accumulation of most late viral mRNAs. Interestingly, the L4 region also encodes for a second related protein, L4-22K, which share the 105 amino-terminal amino acids with L4-33K. Here we show that L4-22K both in vivo and in vitro stimulates transcription from the MLP in a DE sequence dependent manner. We also show that the viral pIX promoter is a natural target, activated by L4-22K. Interestingly, the position of the L4-22K DNA binding site in a promoter does not appear to be critical for function. Thus, tethering L4-22K, as a BPV E2 DNA binding domain fusion protein either to a position upstream or downstream of the MLP start site, or upstream of a minimal E1B promoter, resulted in an activation of transcription. Collectively, our results are compatible with the hypothesis that L4-22K may be the elusive component of DEF-A that partakes in activation of the MLP.
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| 2. |
- Banabazi, Mohammad Hossein
(författare)
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Epidemiology, pathogenesis, and diagnosis of Aleutian disease caused by Aleutian mink disease virus: a literature review with a perspective of genomic breeding for disease control in American mink (Neogale vison)
- 2023
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Ingår i: Virus Research. - 0168-1702 .- 1872-7492. ; 336
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Forskningsöversikt (refereegranskat)abstract
- Aleutian disease (AD) is a multi-systemic infectious disease in American mink (Neogale vison) caused by the Aleutian mink disease virus (AMDV). Commonly referred to as mink plasmacytosis, AD is an economically significant disease in mink-breeding countries. Aleutian disease mainly induces weight loss, lower fertility, and dropped pelt quality in adults and can result in acute interstitial pneumonia with high mortality rates in kits. In this review, we employed the scientific literature on AD over the last 70 years to discuss the historical and contemporary status of AD outbreaks and seroprevalence in mink farming countries. We also explained different forms of AD and the differences between the pathogenicity of the virus in kits and adults. The application of the available AD serological tests in AD control strategies was argued. We explained how selection programs could help AD control and proposed different approaches to selecting animals for building AD-tolerant herds. The advantages of genomic selection for AD tolerance over traditional breeding strategies were discussed in detail. We also explained how genomic selection could help AD control by selecting tolerant animals for the next generation based on genome-wide single nucleotide polymorphisms (SNP) data and the challenges of implementing genomic selection for AD tolerance in the mink industry. This review collected the information required for designing successful breeding programs for AD tolerance. Examples of the application of information are presented, and data gaps are highlighted. We showed that AD tolerance is necessary to be among the traits that animals are selected for in the mink industry.
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| 3. |
- Blomström, Anne-Lie, et al.
(författare)
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Detection of a novel porcine boca-like virus in the background of porcine circovirus type 2 induced postweaning multisystemic wasting syndrome
- 2009
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Ingår i: Virus Research. - : Elsevier BV. - 0168-1702 .- 1872-7492. ; 146, s. 125-129
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Tidskriftsartikel (refereegranskat)abstract
- Porcine circovirus type 2 (PCV-2) has been found to be the causative agent of postweaning multisystemic wasting syndrome (PMWS). However, PCV-2 is a ubiquitous virus in the swine population and a majority of pigs infected with PCV-2 do not develop the disease. Different factors such as age, maintenance, the genetics of PCV-2, other pathogens, etc. have been suggested to contribute to the development of PMWS. However, so far no proven connection between any of these factors and the disease development has been found. In this study we explored the possible presence of other so far unknown DNA containing infectious agents in lymph nodes collected from Swedish pigs with confirmed PMWS through random amplification and high-throughput sequencing. Although the vast majority of the amplified genetic sequences belonged to PCV-2, we also found genome sequences of Torque Teno virus (TTV) and of a novel parvovirus. The detection of TTV was expected since like PCV-2, TTV has been found to have high prevalence in pigs around the world. We were able to amplify a longer region of the parvovirus genome, consisting of the entire NP1 and partial VP1/2. By comparative analysis of the nucleotide sequences and phylogenetic studies we propose that this is a novel porcine parvovirus, with genetic relationship to bocaviruses. (C) 2009 Elsevier B.V. All rights reserved.
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| 4. |
- Blomström, Anne-Lie, et al.
(författare)
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Studies of porcine circovirus type 2, porcine boca-like virus and torque teno virus indicate the presence of multiple viral infections in postweaning multisystemic wasting syndrome pigs
- 2010
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Ingår i: Virus Research. - : Elsevier BV. - 0168-1702 .- 1872-7492. ; 152, s. 59-64
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Tidskriftsartikel (refereegranskat)abstract
- In a previous study, using random amplification and large-scale sequencing technology, we identified a novel porcine parvovirus belonging to the genus Bocavirus in the background of porcine circovirus type 2 (PCV-2) in Swedish pigs with postweaning multisystemic wasting syndrome (PMWS). In addition to bocavirus we demonstrated the presence of torque teno virus (TTV) genogroups 1 and 2 in these cases of PMWS, indicating the simultaneous presence of several viruses in this disease complex. In the present study, 34 PMWS-affected animals and 24 pigs without PMWS were screened by PCR for the presence of PCV-2, TTV-1, TTV-2 and porcine boca-like virus (Pbo-likeV). The studies revealed the following infection rates in the PMWS-affected pigs: PCV-2 100%, TTV-1 77%, TTV-2 94% and Pbo-likeV 88%. In comparison. the pigs without PMWS had the following rates: PCV-2 80%, TTV-1 79%, TTV-2 83% and Pbo-likeV 46%. The sequence identity between the different Swedish Pbo-likeV sequences ranged between 98% and 100%. By checking co-infection, it was found that 71% of the PMWS-affected pigs harbor simultaneously all these viruses. As a contrast, in the group without PMWS only 33% of the animals were positive simultaneously for these viruses. These observations indicate a multiple viral infection in PMWS-affected pigs. It has to be studied further if the clinical manifestation of PMWS might be due to synergistic effects of different viruses acting together. (C) 2010 Elsevier B.V. All rights reserved.
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| 5. |
- Byg, Luise M., et al.
(författare)
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NF-kappa B signalling is attenuated by the E7 protein from cutaneous human papillomaviruses
- 2012
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Ingår i: Virus Research. - : Elsevier BV. - 1872-7492 .- 0168-1702. ; 169:1, s. 48-53
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Tidskriftsartikel (refereegranskat)abstract
- The high-risk Alpha-types of human papillomavirus (HPV) are the causative agent of cervical cancer, which is the second major cause of death among women worldwide. Recent investigations have shown that E7 from the Alpha-papillomavirus HPV-16 interacts with IKK alpha and IKK beta of the IKK complex in the NF-kappa B pathway leading to an attenuation of the activity. There is a possible link between development of non-melanoma skin cancer and cutaneous Beta-papillomavirus but if these HPV types attenuate the NF-kappa B pathway is unclear. Seven different E7 proteins, representing four out of the five different species of the Beta genus (HPV-20, -37, -38, -92, -93 and -96) and one from the Gamma genus (HPV-4) were investigated for potential modulation of the NF-kappa B pathway in U2OS cells. Our results demonstrate that E7 from all the cutaneous HPV types were capable of inhibiting the NF-kappa B activity as well as E7 from HPV-16. In addition, E7 proteins from the cutaneous HPV types demonstrated interaction with IKK alpha but not with IKK beta. The deregulation of the NF-kappa B pathway by cutaneous HPVs might contribute to the pathogenesis of non-melanoma skin cancers and its precursors. (C) 2012 Elsevier B.V. All rights reserved.
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| 6. |
- Cholleti, Harindranath, et al.
(författare)
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Equine arteritis virus induced cell death is associated with activation of the intrinsic apoptotic signalling pathway
- 2013
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Ingår i: Virus Research. - : Elsevier BV. - 0168-1702 .- 1872-7492. ; 171:1, s. 222-226
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Tidskriftsartikel (refereegranskat)abstract
- Equine arteritis virus (EAV) causes a respiratory and reproductive disease in horses, equine viral arteritis. Though cell death in infection with EAV is considered to occur by apoptosis, the underlying molecular mechanism has not been extensively elucidated. We investigated the expression of mRNA of pro-apoptotic and caspase genes during EAV infection in BHK21 cells, a well-established cell type for EAV replication. Using a SYBR Green real-time PCR, mRNA of p53, Bax, caspase 3 and caspase 9 were found up-regulated in a time dependent manner in EAV infected cells. Western blot analysis for caspase 3 and caspase 9 showed expression of cleaved forms of these proteins during EAV infection. In addition, a luminescence-based cell assay for caspase 3/7 activation as a hallmark in apoptosis confirmed apoptotic cell death. The findings demonstrate that cell death in EAV infected BHK21 cells results from apoptosis mediated through the intrinsic signalling pathway.
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| 7. |
- Christ, Wanda, et al.
(författare)
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Sars-cov-2 variant-specific differences in inhibiting the effects of the pkr-activated integrated stress response
- 2024
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Ingår i: Virus Research. - : Elsevier. - 0168-1702 .- 1872-7492. ; 339
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Tidskriftsartikel (refereegranskat)abstract
- The integrated stress response (ISR) is a eukaryotic cell pathway that triggers translational arrest and the formation of stress granules (SGs) in response to various stress signals, including those caused by viral infections. The SARS-CoV-2 nucleocapsid protein has been shown to disrupt SGs, but SARS-CoV-2 interactions with other components of the pathway remains poorly characterized. Here, we show that SARS-CoV-2 infection triggers the ISR through activation of the eIF2α-kinase PKR while inhibiting a variety of downstream effects. In line with previous studies, SG formation was efficiently inhibited and the induced eIF2α phosphorylation only minimally contributed to the translational arrest observed in infected cells. Despite ISR activation and translational arrest, expression of the stress-responsive transcription factors ATF4 and CHOP was not induced in SARS-CoV-2 infected cells. Finally, we found variant-specific differences in the activation of the ISR between ancestral SARS-CoV-2 and the Delta and Omicron BA.1 variants in that Delta infection induced weaker PKR activation while Omicron infection induced higher levels of p-eIF2α, and greatly increased SG formation compared to the other variants. Our results suggest that different SARS-CoV-2 variants can affect normal cell functions differently, which can have an impact on pathogenesis and treatment strategies.
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| 8. |
- Corrêa Giron, Carolina, et al.
(författare)
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On the interactions of the receptor-binding domain of SARS-CoV-1 and SARS-CoV-2 spike proteins with monoclonal antibodies and the receptor ACE2
- 2020
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Ingår i: Virus Research. - : Elsevier. - 0168-1702 .- 1872-7492. ; 285
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Tidskriftsartikel (refereegranskat)abstract
- A new betacoronavirus named SARS-CoV-2 has emerged as a new threat to global health and economy. A promising target for both diagnosis and therapeutics treatments of the new disease named COVID-19 is the coronavirus (CoV) spike (S) glycoprotein. By constant-pH Monte Carlo simulations and the PROCEEDpKa method, we have mapped the electrostatic epitopes for four monoclonal antibodies and the angiotensin-converting enzyme 2 (ACE2) on both SARS-CoV-1 and the new SARS-CoV-2 S receptor binding domain (RBD) proteins. We also calculated free energy of interactions and shown that the S RBD proteins from both SARS viruses binds to ACE2 with similar affinities. However, the affinity between the S RBD protein from the new SARS-CoV-2 and ACE2 is higher than for any studied antibody previously found complexed with SARS-CoV-1. Based on physical chemical analysis and free energies estimates, we can shed some light on the involved molecular recognition processes, their clinical aspects, the implications for drug developments, and suggest structural modifications on the CR3022 antibody that would improve its binding affinities for SARS-CoV-2 and contribute to address the ongoing international health crisis.
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| 9. |
- Cuevas Romero, Julieta Sandra, et al.
(författare)
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Long-term RNA persistence of Porcine rubulavirus (PorPV-LPMV) after an outbreak of a natural infection: The detection of viral mRNA in sentinel pigs suggests viral transmission
- 2014
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Ingår i: Virus Research. - : Elsevier BV. - 0168-1702 .- 1872-7492. ; 188, s. 155-161
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Tidskriftsartikel (refereegranskat)abstract
- The persistence of porcine rubulavirus (PorPV-LPMV) in five pigs that had survived an outbreak of a natural infection was determined. After the resolution of the outbreak, each animal was housed in an isolation pen together with one sentinel pig. Approximately every 2 months thereafter one group of animals was euthanized and tissue samples taken for virological and serological analysis. Infectious virus was not isolated from any samples; antibodies to PorPV-LPMV were detected in convalescent pigs by virus neutralisation test and blocking ELISA but not in sentinel pigs. PorPV-LPMV mRNA of the nucleoprotein (NP) and phosphoprotein (P) genes was detected by a nested polymerase chain reaction (nPCR) in samples of trigeminal and optic nerves, cervical spinal cord, tonsils, salivary gland, lung and pancreas from convalescent pigs. mRNA was also detected in the midbrain, corpus callosum, or olfactory bulb in four out of five pigs by nRT-PCR, this result was confirmed by the sequencing of a 260 bp PCR product of P gene region. The highest average viral copies/mu g of total RNA occurred in the olfactory bulb and pancreas tissues of convalescent pigs and midbrain, tonsil and pancreas of sentinel pigs housed with the convalescent pigs. Satellitosis and gliosis of the midbrain, olfactory bulb, corpus callosum, medulla oblongata or choroid plexus were microscopically observed in four convalescent pigs. The control pig remained negative in all tests. The results indicate that PorPV-LPMV mRNA persists and induces a durable humoral immune response in pigs that have recovered from a natural infection. After a possible reactivation of the virus, it was transmitted to sentinel pigs in contact with the convalescent pigs. (C) 2014 Elsevier B.V. All rights reserved.
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| 10. |
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