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FEMS Immunology and Medical Microbiology Mar 2012Enteroviral infections go usually unnoticed, even during pregnancy, yet some case histories and mouse experiments indicate that these viruses may be transmitted...
Enteroviral infections go usually unnoticed, even during pregnancy, yet some case histories and mouse experiments indicate that these viruses may be transmitted vertically. More frequently, however, transmission occurs by (fecal) contamination during and shortly after birth. The aim of this study was to investigate the effect of maternal infection in mice (1) on gravidity outcome and (2) on subsequent challenge of the offspring with the same virus. CD1 outbred female mice were infected by the oral route with coxsackievirus B4 strain E2 or mock-infected at days 4, 10, or 17 of gestation. Weight and signs of sickness were noted daily. Pups were infected at day 25 after birth (4 days postweaning). Organs (brain, pancreas, and heart) were analyzed for viral RNA and histopathology. We observed that maternal infection at day 4 or day 17 of gestation had little effect on pregnancy outcome, whereas infection at day 10 affected dams and/or offspring. Infection of pups resulted in severe inflammation of the pancreas, but only when dams were previously infected, especially at day 17. The blood glucose levels were elevated. Because no trace of infection was found at the time of challenge, a role for immunopathology is suggested.
Topics: Animals; Blood Glucose; Brain; Coxsackievirus Infections; Enterovirus B, Human; Female; Histocytochemistry; Hyperglycemia; Infectious Disease Transmission, Vertical; Male; Mice; Myocardium; Pancreas; Pregnancy; Pregnancy Complications, Infectious; Weight Gain
PubMed: 22066931
DOI: 10.1111/j.1574-695X.2011.00886.x -
Transplantation Proceedings 2010Porcine organs are valuable candidate materials for xenotransplantation to humans. Long-term maintenance of well functioning transplants is a prerequisite for success....
Porcine organs are valuable candidate materials for xenotransplantation to humans. Long-term maintenance of well functioning transplants is a prerequisite for success. Transplanted organs may be damaged by immune reactions or by infectious agents in hosts. Human herpesviruses (HHVs) establish life-long latency in humans after a primary infection. They can be reactivated with various stimuli, including immunosuppression. This study was performed to verify the infectivity of some HHVs toward porcine cells. PK-15 cells infected with HHV-1 and HHV-2 showed cytopathology from 1 day after infection. Immunofluorescent (IF) staining of HHV-1- and HHV-2-infected PK-15 cells with respective antibodies demonstrated the expression of the respective viral antigens. Permissiveness of PK-15 to HHV-1 and -2 was confirmed by an infection test on Vero cells. Islet cells infected with HHV-5 showed no gross morphologic changes during the experimental course. A limited portion of islet cells reacted only to anti-IE1 and anti-IE2, but not to anti-UL44 or anti-gB antibody by IF staining, whereas a small portion of endothelial cells reacted to anti-IEs and anti-UL44, but not to anti-gB antibody. HHV-1 and -2 can permissively infect porcine cells, but HHV-5 infects a small proportion of cells with limited viral protein expression. HHV-4 could not transform peripheral blood mononuclear cells from miniature pigs. Collectively, because some HHVs can infect and damage porcine cells or impair their functions, HHVs should be cautiously monitored and controlled in humans when porcine cells or organs are transplanted to human beings.
Topics: Animals; Antigens, Viral; Chlorocebus aethiops; Epstein-Barr Virus Infections; Herpes Genitalis; Herpes Simplex; Herpesviridae Infections; Herpesvirus 1, Human; Herpesvirus 2, Human; Herpesvirus 4, Human; Humans; Islets of Langerhans; Swine; Swine Diseases; Swine, Miniature; Transplantation, Heterologous; Vero Cells
PubMed: 20692426
DOI: 10.1016/j.transproceed.2010.05.081 -
Virulence Oct 2017Although known as cytolytic viruses, group B coxackieviruses (CVB) are able to establish a persistent infection in vitro and in vivo. Viral persistence has been reported...
INTRODUCTION
Although known as cytolytic viruses, group B coxackieviruses (CVB) are able to establish a persistent infection in vitro and in vivo. Viral persistence has been reported as a key mechanism in the pathogenesis of CVB-associated chronic diseases such as type 1 diabetes (T1D). The impact of CVB4 persistence on human pancreas ductal-like cells was investigated.
METHODS
A persistent CVB4 infection was established in ductal-like cells. PDX-1 expression, resistance to CVB4-induced lysis and CAR expression were evaluated. The profile of cellular microRNAs (miRNAs) was investigated through miRNA-sequencing. Viral phenotypic changes were examined, and genomic modifications were assessed by sequencing of the viral genome.
RESULTS
The CVB4 persistence in ductal-like cells was productive, with continuous release of infectious particles. Persistently infected cells displayed a resistance to CVB4-induced lysis upon superinfection and expression of PDX-1 and CAR was decreased. These changes were maintained even after virus clearance. The patterns of cellular miRNA expression in mock-infected and in CVB4-persistently infected ductal-like cells were clearly different. The persistent infection-derived virus (PIDV) was still able to induce cytopathic effect but its plaques were smaller than the parental virus. Several mutations appeared in various PIDV genome regions, but amino acid substitutions did not affect the predicted site of interaction with CAR.
CONCLUSION
Cellular and viral changes occur during persistent infection of human pancreas ductal-like cells with CVB4. The persistence of cellular changes even after virus clearance supports the hypothesis of a long-lasting impact of persistent CVB infection on the cells.
Topics: Cell Line, Tumor; Coxsackievirus Infections; Enterovirus B, Human; Homeodomain Proteins; Humans; MicroRNAs; Pancreas; Pancreatic Ducts; Trans-Activators; Virus Replication
PubMed: 28112573
DOI: 10.1080/21505594.2017.1284735 -
Journal of Virology Aug 2003Infections with the group B coxsackieviruses either can be asymptomatic or can lead to debilitating chronic diseases. To elucidate the mechanism by which these viruses...
Infections with the group B coxsackieviruses either can be asymptomatic or can lead to debilitating chronic diseases. To elucidate the mechanism by which these viruses cause chronic disease, we developed a mouse model of chronic pancreatitis by using a virulent variant of coxsackievirus B4, CVB4-V. Infection with CVB4-V results in an early, severe pancreatitis, which can lead to mortality or progress to chronic pancreatitis. Chronic pancreatitis, in this model, is due to immunopathological mechanisms. We investigated whether interleukin-12 (IL-12) could modulate the outcome of CVB4-V infection. Eighty-five percent of the infected mice treated with 500 ng of IL-12 survived, whereas all untreated mice succumbed. To understand the mechanism underlying the beneficial effect of IL-12, we investigated the role of gamma interferon (IFN-gamma). Three lines of evidence suggest that the protective effect of IL-12 is due to IFN-gamma. First, administration of IL-12 increased the production of endogenous IFN-gamma in CVB4-V-infected mice. Both NK and NKT cells were identified as the source of IFN-gamma. Second, IFN-gamma knockout mice treated with IL-12 succumbed to infection with CVB4-V. Third, wild-type mice treated with IFN-gamma survived infection with CVB4-V. Due to the antiviral effects of IFN-gamma, we examined whether IL-12 treatment affected viral replication. Administration of IL-12 did not decrease viral replication in the pancreas, but it did prevent extensive tissue damage and the subsequent development of chronic pancreatitis. The data suggest that IL-12 treatment during CVB4-V infection is able to suppress the immunopathological mechanisms that lead to chronic disease.
Topics: Animals; Chronic Disease; Enterovirus B, Human; Enterovirus Infections; Interferon-gamma; Interleukin-12; Killer Cells, Natural; Mice; Mice, Inbred BALB C; Pancreas; Pancreatitis; Recombinant Proteins; Virulence
PubMed: 12857896
DOI: 10.1128/jvi.77.15.8272-8279.2003 -
Acta Medica Italica Di Malattie... Feb 1948
Topics: Humans; Pancreas; Tuberculosis
PubMed: 18860392
DOI: No ID Found -
Current Topics in Microbiology and... 1997
Review
Topics: Animals; Base Sequence; Chromosome Mapping; Coxsackievirus Infections; Enterovirus B, Human; Heart; Humans; Mice; Mice, Inbred C3H; Molecular Sequence Data; Pancreas; Sequence Alignment; Virulence
PubMed: 9294932
DOI: 10.1007/978-3-642-60687-8_11 -
Nature Sep 2000Animal donors such as pigs could provide an alternative source of organs for transplantation. However, the promise of xenotransplantation is offset by the possible...
Animal donors such as pigs could provide an alternative source of organs for transplantation. However, the promise of xenotransplantation is offset by the possible public health risk of a cross-species infection. All pigs contain several copies of porcine endogenous retroviruses (PERV), and at least three variants of PERV can infect human cell lines in vitro in co-culture, infectivity and pseudotyping experiments. Thus, if xenotransplantation of pig tissues results in PERV viral replication, there is a risk of spreading and adaptation of this retrovirus to the human host. C-type retroviruses related to PERV are associated with malignancies of haematopoietic lineage cells in their natural hosts. Here we show that pig pancreatic islets produce PERV and can infect human cells in culture. After transplantation into NOD/SCID (non-obese diabetic, severe combined immunodeficiency) mice, we detect ongoing viral expression and several tissue compartments become infected. This is the first evidence that PERV is transcriptionally active and infectious cross-species in vivo after transplantation of pig tissues. These results show that a concern for PERV infection risk associated with pig islet xenotransplantation in immunosuppressed human patients may be justified.
Topics: Animals; Cells, Cultured; Endogenous Retroviruses; Humans; Islets of Langerhans; Mice; Mice, Inbred NOD; Mice, SCID; Molecular Sequence Data; Pancreas Transplantation; RNA, Messenger; RNA, Viral; Retroviridae Infections; Reverse Transcriptase Polymerase Chain Reaction; Species Specificity; Swine; Transplantation Chimera; Transplantation, Heterologous
PubMed: 10993079
DOI: 10.1038/35024089 -
Current Gastroenterology Reports Apr 1999According to the Atlanta classification, the most widely accepted clinically based classification system for acute pancreatitis, four pathologic entities of fluid... (Review)
Review
According to the Atlanta classification, the most widely accepted clinically based classification system for acute pancreatitis, four pathologic entities of fluid collections and necrosis are recognized. Acute fluid collections occur early as an exudative reaction to the pancreatic inflammation, have no fibrous wall, and resolve spontaneously. Pancreatic necrosis, the most severe form of acute pancreatitis, is diagnosed on dynamic contrast-enhanced computerized tomography and requires early aggressive cardiorespiratory resuscitation, nutritional support, and appropriate systemic antibiotics to prevent superinfection. Development of infection (infected necrosis) is the indication for operative debridement, preferably as late in the course of the disease as possible. Acute pseudocysts are collections of pancreatic, enzyme-rich fluid caused by pancreatic ductal disruption that occur 3 to 6 weeks after onset of acute pancreatitis and have a well-defined, nonepithelial fibrous wall. If communication with the ductal system is present, internal enteric drainage (either operative or endoscopic) is more effective; if communication is not present, the pseudocysts are amenable to percutaneous drainage. A pancreatic abscess is an infected, circumscribed peripancreatic collection, associated with minimal or no parenchymal necrosis, that occurs late (4 to 6 weeks) after onset of severe pancreatitis and may represent an infected pseudocyst; percutaneous drainage is the treatment of choice.
Topics: Abscess; Diagnostic Imaging; Drainage; Humans; Pancreas; Pancreatic Pseudocyst; Pancreatitis, Acute Necrotizing
PubMed: 10980941
DOI: 10.1007/s11894-996-0013-9 -
The Australian and New Zealand Journal... Apr 1995The pancreas is the fourth most commonly injured intra-abdominal organ in children who sustain blunt abdominal trauma. Appropriate management of the injured pancreas has...
The pancreas is the fourth most commonly injured intra-abdominal organ in children who sustain blunt abdominal trauma. Appropriate management of the injured pancreas has been controversial. With the advent of the computerized tomography scan, paediatric surgeons have tended to manage pancreatic injuries non-operatively. However, if pseudocysts develop, non-operative management may necessarily entail a long hospital course involving total parenteral nutrition, drainage procedures and attendant morbidity. The critical element in planning therapy is to determine the status of the pancreatic duct. We have recently encountered five children who suffered blunt pancreatic injury where the main pancreatic duct was determined to have been transected. These children underwent spleen preserving distal pancreatectomy with resultant shorter hospital stays and minimal long-term morbidity. We suggest that in children with pancreatic injury where the main pancreatic duct has been transected early operative management rather than non-operative therapy is the procedure of choice. Endoscopic retrograde cholangiopancreatography should be used to determine the status of the pancreatic duct. This modality can be both diagnostic and therapeutic in appropriate circumstances.
Topics: Bacterial Infections; Child; Child, Preschool; Cholangiopancreatography, Endoscopic Retrograde; Drainage; Female; Follow-Up Studies; Humans; Laparotomy; Length of Stay; Ligation; Male; Pancreas; Pancreatectomy; Pancreatic Ducts; Pancreatic Pseudocyst; Spleen; Wounds, Nonpenetrating
PubMed: 7717941
DOI: 10.1111/j.1445-2197.1995.tb00620.x -
Journal of Virology Dec 2010Autophagy can play an important part in protecting host cells during virus infection, and several viruses have developed strategies by which to evade or even exploit...
Autophagy can play an important part in protecting host cells during virus infection, and several viruses have developed strategies by which to evade or even exploit this homeostatic pathway. Tissue culture studies have shown that poliovirus, an enterovirus, modulates autophagy. Herein, we report on in vivo studies that evaluate the effects on autophagy of coxsackievirus B3 (CVB3). We show that in pancreatic acinar cells, CVB3 induces the formation of abundant small autophagy-like vesicles and permits amphisome formation. However, the virus markedly, albeit incompletely, limits the fusion of autophagosomes (and/or amphisomes) with lysosomes, and, perhaps as a result, very large autophagy-related structures are formed within infected cells; we term these structures megaphagosomes. Ultrastructural analyses confirmed that double-membraned autophagy-like vesicles were present in infected pancreatic tissue and that the megaphagosomes were related to the autophagy pathway; they also revealed a highly organized lattice, the individual components of which are of a size consistent with CVB RNA polymerase; we suggest that this may represent a coxsackievirus replication complex. Thus, these in vivo studies demonstrate that CVB3 infection dramatically modifies autophagy in infected pancreatic acinar cells.
Topics: Analysis of Variance; Animals; Autophagy; Blotting, Western; Coxsackievirus Infections; Enterovirus B, Human; Green Fluorescent Proteins; HeLa Cells; Humans; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Microscopy, Confocal; Microscopy, Electron, Transmission; Microscopy, Immunoelectron; Pancreas; Phagosomes
PubMed: 20861268
DOI: 10.1128/JVI.01417-10