scholarly journals Anion homeostasis is important for non-lytic release of BK polyomavirus from infected cells

Open Biology ◽  
2015 ◽  
Vol 5 (8) ◽  
pp. 150041 ◽  
Author(s):  
Gareth L. Evans ◽  
Laura G. Caller ◽  
Victoria Foster ◽  
Colin M. Crump

BK polyomavirus (BKPyV) is a member of a family of potentially oncogenic viruses, whose reactivation can cause severe pathological conditions in transplant patients, leading to graft rejection. As with many non-enveloped viruses, it is assumed that virus release occurs through lysis of the host cell. We now show the first evidence for a non-lytic release pathway for BKPyV and that this pathway can be blocked by the anion channel inhibitor DIDS. Our data show a dose-dependent effect of DIDS on the release of BKPyV virions. We also observed an accumulation of viral capsids in large LAMP-1-positive acidic organelles within the cytoplasm of cells upon DIDS treatment, suggesting potential late endosome or lysosome-related compartments are involved in non-lytic BKPyV release. These data highlight a novel mechanism by which polyomaviruses can be released from infected cells in an active and non-lytic manner, and that anion homeostasis regulation is important in this pathway.

2011 ◽  
Vol 91 (9) ◽  
pp. 997-1004 ◽  
Author(s):  
Giovanni Stallone ◽  
Barbara Infante ◽  
Paola Pontrelli ◽  
Maddalena Gigante ◽  
Eustacchio Montemurno ◽  
...  

2020 ◽  
Vol 2 (7A) ◽  
Author(s):  
Sophia Ho ◽  
Laura Caller ◽  
Rupert Beale ◽  
Colin Crump

BK polyomavirus (BKPyV) is a small, non-enveloped dsDNA virus that infects 70-90% of the world's population and causes a lifelong, silently persistent infection. In immunocompromised individuals, BKPyV replication can result in serious pathology. Bone marrow transplant patients can develop a haemorrhagic cystitis, and in kidney transplant patients BKPyV replication can provoke a nephropathy that leads to deterioration of allograft function and eventual loss of the transplanted organ. There are currently no antiviral treatments with clinical efficacy against BKPyV associated nephropathy. While the life cycles of non-enveloped viruses are often assumed to require cell lysis to release progeny virions, we have evidence to suggest that BKPyV exits the cell via non-lytic means using an unconventional secretory pathway. We have investigated the effects of knocking out cellular genes thought to be involved in unconventional secretory pathways that bypass the Golgi apparatus on the release of BKPyV. We observe decreased BKPyV release from cells that have undergone CRISPR-mediated knockout of Golgi Reassembly Stacking Protein (GORASP) 1 or 2. Investigation of BKPyV-induced changes to the plasma membrane of infected cells demonstrated increased cell surface expression of transmembrane proteins normally resident in the endoplasmic reticulum. This appears to be inhibited by the knockout of GORASP1 or 2, suggesting that virions and ER markers are secreted via a common pathway in infected cells. These experiments are uncovering novel virus-host interactions that, when targeted, could help prevent BKPyV-associated nephropathy and allograft loss.


Author(s):  
K.S. Pavlova ◽  
D.S. Mdinaradze

По данным ВОЗ, рекомендации врача выполняют не более 50 пациентов. В конечном итоге это приводит к снижению или отсутствию эффекта от назначаемого лечения. В связи с этим во всех последних международных и национальных руководствах говорится о необходимости учета предпочтений пациента при выборе терапии. Аллерген-специфическая иммунотерапия (АСИТ) является одним из основных методов лечения аллергических заболеваний, таких как аллергический ринит, конъюнктивит и атопическая бронхиальная астма, обладает болезнь-модифицирующими свойствами и долгосрочным эффектом после окончания лечения. АСИТ относится к профилактическому и продолжительному методу (рекомендовано на протяжении не менее 3 лет), что часто является причиной снижения приверженности к терапии. В различных исследованиях подтвержден зависимый от дозы аллергена эффект АСИТ, а следовательно, изменение режимов или сокращение сроков терапии могут влиять на конечный результат. При недостаточной эффективности АСИТ необходимо в первую очередь рассматривать вероятность низкого комплаенса. Сублингвальная АСИТ (СЛИТ) требует от пациента высокой вовлеченности в процесс лечения. Задачей врача в данном случае становится повышение терапевтического сотрудничества как одного из важнейших факторов обеспечения эффективности СЛИТ. Основными способами в данном случае являются улучшение понимания пациентом цели терапии и регулярный контроль со стороны врача.According to WHO at last 50 of the patient dont follow doctors recommendations. Ultimately, this leads to a decrease or absence of the treatment effect. In this regard, all the latest international and national guidelines mention the need to take into account the patients preferences in the choice of therapy. Allergen-specific immunotherapy (AIT) is one of the main methods of treatment of allergic diseases such as allergic rhinitis, allergic conjunctivitis and atopic asthma, and has disease modifying properties and the long-term efficacy after stop treatment. AIT refers to a preventive and long-term method (recommended for at least 3 years), that is often the cause of reduced adherence to therapy. Various studies have confirmed the dose-dependent effect of AIT, and, consequently, changes in regimens or shortening of therapy may affect the end result. In case of insufficient effectiveness of AIT, the probability of low compliance should be considered first of all. Sublingual AIT (SLIT) requires the patient to be highly involved in the treatment process. The task of the doctor in this case is increasing therapeutic cooperation, as one of the most important factors to ensure the effectiveness of SLIT. The main methods in this case are to improve the patients understanding of the purpose of the therapy and regular monitoring by the doctor.


Author(s):  
Shiva Naseri ◽  
Gabriele Griffanti ◽  
William C. Lepry ◽  
Vimal B. Maisuria ◽  
Nathalie Tufenkji ◽  
...  

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Timo W. M. De Groof ◽  
Elizabeth G. Elder ◽  
Eleanor Y. Lim ◽  
Raimond Heukers ◽  
Nick D. Bergkamp ◽  
...  

AbstractLatent human cytomegalovirus (HCMV) infection is characterized by limited gene expression, making latent HCMV infections refractory to current treatments targeting viral replication. However, reactivation of latent HCMV in immunosuppressed solid organ and stem cell transplant patients often results in morbidity. Here, we report the killing of latently infected cells via a virus-specific nanobody (VUN100bv) that partially inhibits signaling of the viral receptor US28. VUN100bv reactivates immediate early gene expression in latently infected cells without inducing virus production. This allows recognition and killing of latently infected monocytes by autologous cytotoxic T lymphocytes from HCMV-seropositive individuals, which could serve as a therapy to reduce the HCMV latent reservoir of transplant patients.


2011 ◽  
Vol 91 (2) ◽  
pp. 520-525 ◽  
Author(s):  
Salima Mithani ◽  
Michael Kuskowski ◽  
Yelena Slinin ◽  
Areef Ishani ◽  
Edward McFalls ◽  
...  

1987 ◽  
Vol 17 (4) ◽  
pp. 869-873 ◽  
Author(s):  
C. Schmauss ◽  
J.-C. Krieg

SynopsisIn 17 benzodiazepine (BDZ) dependent in-patients a CT scan was performed before initiation of withdrawal therapy. The evaluation of the ventricular to brain ratio (VBR) by standardized and computerized measurements revealed significantly higher mean VBRs for both high-and low-dose BDZ-dependent patients compared to the mean VBR of an age- and sex-matched control group. In addition, the mean VBR of high-dose BDZ-dependent patients (N = 8) was significantly higher than the mean VBR of low-dose BDZ-dependent patients (N = 9). This difference could not be accounted for by the age of the patients or duration of BDZ-dependency and, therefore, suggests a dose-dependent effect of BDZs on the enlargement of internal CSF-spaces. On the other hand, higher values for the width of external CSF-spaces were found to be related to increasing age of the patients and duration of BDZ-dependency.


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