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Journal of Clinical Oncology : Official... Nov 2017Purpose Improvement of cure rates for patients treated with allogeneic hematopoietic stem-cell transplantation (HSCT) will require efforts to decrease treatment-related...
Off-the-Shelf Virus-Specific T Cells to Treat BK Virus, Human Herpesvirus 6, Cytomegalovirus, Epstein-Barr Virus, and Adenovirus Infections After Allogeneic Hematopoietic Stem-Cell Transplantation.
Purpose Improvement of cure rates for patients treated with allogeneic hematopoietic stem-cell transplantation (HSCT) will require efforts to decrease treatment-related mortality from severe viral infections. Adoptively transferred virus-specific T cells (VSTs) generated from eligible, third-party donors could provide broad antiviral protection to recipients of HSCT as an immediately available off-the-shelf product. Patient and Methods We generated a bank of VSTs that recognized five common viral pathogens: Epstein-Barr virus (EBV), adenovirus (AdV), cytomegalovirus (CMV), BK virus (BKV), and human herpesvirus 6 (HHV-6). The VSTs were administered to 38 patients with 45 infections in a phase II clinical trial. Results A single infusion produced a cumulative complete or partial response rate of 92% (95% CI, 78.1% to 98.3%) overall and the following rates by virus: 100% for BKV (n = 16), 94% for CMV (n = 17), 71% for AdV (n = 7), 100% for EBV (n = 2), and 67% for HHV-6 (n = 3). Clinical benefit was achieved in 31 patients treated for one infection and in seven patients treated for multiple coincident infections. Thirteen of 14 patients treated for BKV-associated hemorrhagic cystitis experienced complete resolution of gross hematuria by week 6. Infusions were safe, and only two occurrences of de novo graft-versus host disease (grade 1) were observed. VST tracking by epitope profiling revealed persistence of functional VSTs of third-party origin for up to 12 weeks. Conclusion The use of banked VSTs is a feasible, safe, and effective approach to treat severe and drug-refractory infections after HSCT, including infections from two viruses (BKV and HHV-6) that had never been targeted previously with an off-the-shelf product. Furthermore, the multispecificity of the VSTs ensures extensive antiviral coverage, which facilitates the treatment of patients with multiple infections.
Topics: Adenoviruses, Human; Adult; BK Virus; DNA Virus Infections; DNA Viruses; Female; Hematopoietic Stem Cell Transplantation; Herpesvirus 4, Human; Herpesvirus 6, Human; Humans; Immunotherapy, Adoptive; Male; T-Lymphocytes; Transplantation, Homologous; Treatment Outcome
PubMed: 28783452
DOI: 10.1200/JCO.2017.73.0655 -
Journal of Virology Apr 2022Respiratory syncytial virus (RSV) is a leading cause of pediatric acute respiratory infection worldwide. There are currently no approved vaccines or antivirals to combat...
Respiratory syncytial virus (RSV) is a leading cause of pediatric acute respiratory infection worldwide. There are currently no approved vaccines or antivirals to combat RSV disease. A few transformed cell lines and two historic strains have been extensively used to study RSV. Here, we reported a thorough molecular and cell biological characterization of HEp-2 and A549 cells infected with one of four strains of RSV representing both major subgroups as well as historic and more contemporary genotypes (RSV/A/Tracy [GA1], RSV/A/Ontario [ON], RSV/B/18537 [GB1], and RSV/B/Buenos Aires [BA]) via measurements of viral replication kinetics and viral gene expression, immunofluorescence-based imaging of gross cellular morphology and cell-associated RSV, and measurements of host response, including transcriptional changes and levels of secreted cytokines and growth factors. Infection with the respiratory syncytial virus (RSV) early in life is essentially guaranteed and can lead to severe disease. Most RSV studies have involved either of two historic RSV/A strains infecting one of two cell lines, HEp-2 or A549 cells. However, RSV contains ample variation within two evolving subgroups (A and B), and HEp-2 and A549 cell lines are genetically distinct. Here, we measured viral action and host response in both HEp-2 and A549 cells infected with four RSV strains from both subgroups and representing both historic and more contemporary strains. We discovered a subgroup-dependent difference in viral gene expression and found A549 cells were more potently antiviral and more sensitive, albeit subtly, to viral variation. Our findings revealed important differences between RSV subgroups and two widely used cell lines and provided baseline data for experiments with model systems better representative of natural RSV infection.
Topics: A549 Cells; Antiviral Agents; Cell Line; Host Microbial Interactions; Humans; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Severity of Illness Index; Species Specificity; Virus Replication
PubMed: 35285685
DOI: 10.1128/jvi.01904-21 -
Cureus Jul 2020Multiple public health problems have been caused by various coronavirus strains over the last few years, such as the middle eastern respiratory syndrome (MERS), severe... (Review)
Review
Multiple public health problems have been caused by various coronavirus strains over the last few years, such as the middle eastern respiratory syndrome (MERS), severe acute respiratory syndrome (SARS), and COVID-19. COVID-19, which is also known as coronavirus disease 2019, was first detected in Wuhan, China, and has significantly impacted people's health and lives. Additionally, it has led to a pandemic, and the virus has spread to over 121 countries worldwide. There is numerous information available regarding this virus. A detailed and extensive study of the morphological and histopathological findings will help understand and diagnose the disease. As it is a new disease, it is challenging to understand the mechanism of the action and disease pathology due to the limited availability of data from autopsies or biopsies. However, as the detailed mechanism of injury remains unclear, this paper aims to review the postmortem gross and histopathological findings of various organs that have been affected with coronavirus, focusing on the pulmonary, cardiac, and hematologic findings. This paper emphasizes the postmortem findings of the effect of the coronavirus disease on multiple organ systems. Advance search of the keywords on PubMed was used, limiting the search to the last five years. The eligible article is narrowed based on relevance containing postmortem findings of the novel virus; COVID-19. A total of 25 full-text articles were selected and used in the review of this paper.
PubMed: 32864262
DOI: 10.7759/cureus.9438 -
Viruses Mar 2016The tumorvirus human T-cell lymphotropic virus type 1 (HTLV-1), a member of the delta-retrovirus family, is transmitted via cell-containing body fluids such as blood... (Review)
Review
The tumorvirus human T-cell lymphotropic virus type 1 (HTLV-1), a member of the delta-retrovirus family, is transmitted via cell-containing body fluids such as blood products, semen, and breast milk. In vivo, HTLV-1 preferentially infects CD4⁺ T-cells, and to a lesser extent, CD8⁺ T-cells, dendritic cells, and monocytes. Efficient infection of CD4⁺ T-cells requires cell-cell contacts while cell-free virus transmission is inefficient. Two types of cell-cell contacts have been described to be critical for HTLV-1 transmission, tight junctions and cellular conduits. Further, two non-exclusive mechanisms of virus transmission at cell-cell contacts have been proposed: (1) polarized budding of HTLV-1 into synaptic clefts; and (2) cell surface transfer of viral biofilms at virological synapses. In contrast to CD4⁺ T-cells, dendritic cells can be infected cell-free and, to a greater extent, via viral biofilms in vitro. Cell-to-cell transmission of HTLV-1 requires a coordinated action of steps in the virus infectious cycle with events in the cell-cell adhesion process; therefore, virus propagation from cell-to-cell depends on specific interactions between cellular and viral proteins. Here, we review the molecular mechanisms of HTLV-1 transmission with a focus on the HTLV-1-encoded proteins Tax and p8, their impact on host cell factors mediating cell-cell contacts, cytoskeletal remodeling, and thus, virus propagation.
Topics: Cell Communication; Dendritic Cells; Host-Pathogen Interactions; Human T-lymphotropic virus 1; Humans; T-Lymphocytes; Virus Internalization; Virus Release
PubMed: 27005656
DOI: 10.3390/v8030074 -
Journal of B.U.ON. : Official Journal... 2018Oral squamous cell carcinoma (OSCC) demonstrates an increasing rate due to high risk Human Papilloma Virus (HR-HPV) persistent infection, and also to chronic cigarette... (Review)
Review
Oral squamous cell carcinoma (OSCC) demonstrates an increasing rate due to high risk Human Papilloma Virus (HR-HPV) persistent infection, and also to chronic cigarette and alcohol consumption. Gross chromosomal alterations (polysomy, aneuploidy, intra-chromosome rearrangements) and specific gene aberrations such as amplifications, deletions, point mutations combined or not with epigenetic ones (promoter methylations and miRNA deregulations) are responsible for the progressive transformation of normal squamous cell epithelia to the corresponding malignant. Chromosomal instability (CI) -based on structural or numerical abnormalities- leads to specific abnormal karyotypes combined or not with functional suppressor gene inactivation and oncogene overactivation in solid malignancies, including OSCC. Extensive cytogenetic analyses have shown that gross alterations (gains/losses) in chromosomes 3, 4, 7, 8, 9, 11, 14, 17, 18, 19 and also 20 form different CI patterns in OSCC, which in conjunction with an aggressive phenotype (presence of lymph nodal metastasis) negatively affect the prognosis in the corresponding patients. In the majority of OSCC cases, loss of chromosomal bands are almost equally detected compared with gains regarding the chromosomes referred above. In the current special molecular paper we explored the role of CI in the progression and biological behavior of OSCCs.
Topics: Carcinoma, Squamous Cell; Chromosomal Instability; Humans; Mouth Neoplasms; Prognosis
PubMed: 30610780
DOI: No ID Found -
Vector Borne and Zoonotic Diseases... Sep 2022Outbreaks of African filoviruses often have high mortality, including more than 11,000 deaths among 28,562 cases during the West Africa Ebola outbreak of 2014-2016.... (Review)
Review
Outbreaks of African filoviruses often have high mortality, including more than 11,000 deaths among 28,562 cases during the West Africa Ebola outbreak of 2014-2016. Numerous studies have investigated the factors that contributed to individual filovirus outbreaks, but there has been little quantitative synthesis of this work. In addition, the ways in which the typical causes of filovirus outbreaks differ from other zoonoses remain poorly described. In this study, we quantify factors associated with 45 outbreaks of African filoviruses (ebolaviruses and Marburg virus) using a rubric of 48 candidate causal drivers. For filovirus outbreaks, we reviewed >700 peer-reviewed and gray literature sources and developed a list of the factors reported to contribute to each outbreak (, a "driver profile" for each outbreak). We compare and contrast the profiles of filovirus outbreaks to 200 background outbreaks, randomly selected from a global database of 4463 outbreaks of bacterial and viral zoonotic diseases. We also test whether the quantitative patterns that we observed were robust to the influences of six covariates, country-level factors such as gross domestic product, population density, and latitude that have been shown to bias global outbreak data. We find that, regardless of whether covariates are included or excluded from models, the driver profile of filovirus outbreaks differs from that of background outbreaks. Socioeconomic factors such as trade and travel, wild game consumption, failures of medical procedures, and deficiencies in human health infrastructure were more frequently reported in filovirus outbreaks than in the comparison group. Based on our results, we also present a review of drivers reported in at least 10% of filovirus outbreaks, with examples of each provided.
Topics: Animals; Disease Outbreaks; Ebolavirus; Hemorrhagic Fever, Ebola; Humans; Marburg Virus Disease; Marburgvirus
PubMed: 36084314
DOI: 10.1089/vbz.2022.0020 -
Der Nephrologe 2021The aim of this article is to explain the clinical benefits of the growing knowledge about severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In addition to... (Review)
Review
The aim of this article is to explain the clinical benefits of the growing knowledge about severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In addition to the lungs, SARS-CoV‑2 can invade multiple cell types in other organs, such as the kidneys and replicate there. Important damaging pathways of the virus, such as vascular endotheliitis, thrombotic events and systemic cytokine release are still incompletely understood. Coronavirus disease 2019 (COVID-19) is a systemic disease that necessitates intensive medical care and in particular, internal medicine involvement and represents a major challenge for all disciplines of internal medicine. Among these, nephrology in particular is involved in the fight against COVID-19 in a variety of ways: urine investigations can provide indications of multiple organ involvement, endotheliitis, microthrombi and microcirculation damage, etc. Experience with low serum albumin levels and antithrombin III activity in nephrotic patients helps to point out the decreasing effects of loop diuretics and heparin to other specialist disciplines. Nephrological knowledge of the complications of hypoalbuminemia and "resistance" to diuretics must lead to an early implementation of renal replacement procedures in order to be able to prevent mechanical ventilation in COVID-19 intensive care patients with increased extracellular lung fluid. The kidneys can be used as a seismograph for severe courses of COVID-19 and nephrological knowledge can be brought to use to optimize the intensive medical care for critically ill patients. Both together have the potential to considerably reduce morbidity and mortality further.
PubMed: 33343739
DOI: 10.1007/s11560-020-00470-2 -
Obstetrics and Gynecology Jun 2015The largest-ever recorded outbreak of viral hemorrhagic fever is ongoing. As a result of the epidemic and rural nature of outbreaks, little is published about the... (Review)
Review
The largest-ever recorded outbreak of viral hemorrhagic fever is ongoing. As a result of the epidemic and rural nature of outbreaks, little is published about the Filovirus infections Ebola virus disease and Marburg disease in pregnancy. This review of viral hemorrhagic fever focusing on Marburg and Ebola uses knowledge of disease in nonpregnant individuals and pregnancy-specific data to inform management for pregnant women. Filovirus infection presentation is similar between pregnant and nonpregnant patients, although infections may be more severe in pregnancy. Although labeled as hemorrhagic fevers, Marburg and Ebola do not commonly cause gross bleeding and should be conceptualized as diseases of high gastrointestinal losses. Early, aggressive supportive care is the mainstay of Filovirus infection management with massive fluid resuscitation as the key management principle. Patients often require 5-10 L or more per day of intravenous or oral fluid to maintain circulating blood volume in the setting of ongoing gastrointestinal loss. Fluid shifts warrant aggressive monitoring and correction of potassium levels and acid-base disturbances to prevent life-threatening arrhythmias and metabolic complications. Regardless of maternal survival, fetal loss rates are nearly 100% in Filovirus infection, likely resulting from unchecked transplacental and hematogenous viral spread. High fetal loss rates support the placenta as a difficult-to-eradicate Filovirus infection reservoir. In conclusion, the management of Filovirus infection in pregnancy should focus on stabilizing the mother with intensive monitoring and aggressive fluid and electrolyte repletion as well as maintaining strict infection control to minimize transmission to others.
Topics: Animals; Female; Fluid Therapy; Hemorrhagic Fever, Ebola; Humans; Marburg Virus Disease; Occupational Exposure; Potassium; Pregnancy; Pregnancy Complications, Infectious
PubMed: 26000499
DOI: 10.1097/AOG.0000000000000853 -
Acta Veterinaria Scandinavica Sep 2015Diagnosing the cause of bovine congenital malformations (BCMs) is challenging for bovine veterinary practitioners and laboratory diagnosticians as many known as well as... (Review)
Review
Diagnosing the cause of bovine congenital malformations (BCMs) is challenging for bovine veterinary practitioners and laboratory diagnosticians as many known as well as a large number of not-yet reported syndromes exist. Foetal infection with certain viruses, including bovine virus diarrhea virus (BVDV), Schmallenberg virus (SBV), blue tongue virus (BTV), Akabane virus (AKAV), or Aino virus (AV), is associated with a range of congenital malformations. It is tempting for veterinary practitioners to diagnose such infections based only on the morphology of the defective offspring. However, diagnosing a virus as a cause of BCMs usually requires laboratory examination and even in such cases, interpretation of findings may be challenging due to lack of experience regarding genetic defects causing similar lesions, even in cases where virus or congenital antibodies are present. Intrauterine infection of the foetus during the susceptible periods of development, i.e. around gestation days 60-180, by BVDV, SBV, BTV, AKAV and AV may cause malformations in the central nervous system, especially in the brain. Brain lesions typically consist of hydranencephaly, porencephaly, hydrocephalus and cerebellar hypoplasia, which in case of SBV, AKAV and AV infections may be associated by malformation of the axial and appendicular skeleton, e.g. arthrogryposis multiplex congenita. Doming of the calvarium is present in some, but not all, cases. None of these lesions are pathognomonic so diagnosing a viral cause based on gross lesions is uncertain. Several genetic defects share morphology with virus induced congenital malformations, so expert advice should be sought when BCMs are encountered.
Topics: Animals; Cattle; Cattle Diseases
PubMed: 26399846
DOI: 10.1186/s13028-015-0145-8 -
Brazilian Journal of Microbiology :... Dec 2022Canine distemper virus (CDV) and canine circovirus (CanineCV) have been described worldwide in multi-systemic disease in dogs. Both agents may be occasionally associated...
Canine distemper virus (CDV) and canine circovirus (CanineCV) have been described worldwide in multi-systemic disease in dogs. Both agents may be occasionally associated with other viral pathogens, but reports of coinfection by CDV and CanineCV associated with disease are rare. In this article, we report a coinfection between CDV and CanineCV detected during an investigation of viral agents involved in multisystemic disease in dogs in Southern Brazil. Molecular testing by PCR in lungs and intestines of 77 dogs necropsied in pathology services (2015-2020) revealed several single and mixed viral infections, including a CDV/CanineCV coinfection. In the case reported here, gross and histological findings were compatible with CDV pathology (bronchointerstitial pneumonia and viral intracytoplasmatic inclusions in pneumocytes and transitional epithelial cells of urinary bladder). CanineCV DNA and CDV antigens were detected in lung and intestine fragments by PCR and immunohistochemistry, respectively. CanineCV PCR amplicons subjected to nucleotide sequencing showed > 98.6% nucleotide identity with CanineCV sequences from GenBank. Although the role of CanineCV in the pathogenesis of the reported case could not be determined, our results show that CanineCV may be associated with other viral infections in cases of multisystemic disease in dogs. These results reinforce the circulation of CanineCV in dogs in Brazil and highlight the importance of including this virus in the list of differential diagnoses of respiratory and gastroenteric infectious diseases in dogs.
Topics: Dogs; Animals; Distemper Virus, Canine; Circovirus; Brazil; Coinfection; Nucleotides; Dog Diseases
PubMed: 35881236
DOI: 10.1007/s42770-022-00803-4