A 68-year old man diagnosed with Middle East Respiratory Syndrome-Coronavirus (MERS-CoV) presented with multiple pneumonic infiltrations on his chest X-ray, and the patient was placed on a mechanical ventilator because of progressive respiratory failure. Urinary protein excretion steadily increased for a microalbumin to creatinine ratio of 538.4 mg/g Cr and a protein to creatinine ratio of 3,025.8 mg/g Cr. The isotope dilution mass spectrometry traceable serum creatinine level increased to 3.0 mg/dL. We performed a kidney biopsy 8 weeks after the onset of symptoms. Acute tubular necrosis was the main finding, and proteinaceous cast formation and acute tubulointerstitial nephritis were found. There were no electron dense deposits observed with electron microscopy. We could not verify the virus itself by in situ hybridization and confocal microscopy (MERS-CoV co-stained with dipeptidyl peptidase 4). The viremic status, urinary virus excretion, and timely kidney biopsy results should be investigated with thorough precautions to reveal the direct effects of MERS-CoV with respect to renal complications.
Aged ; Biopsy ; Coronavirus Infections/*diagnosis/virology ; Creatinine/blood/urine ; Dipeptidyl Peptidase 4/metabolism ; Humans ; In Situ Hybridization, Fluorescence ; Kidney/metabolism/*pathology ; Male ; Microscopy, Confocal ; Microscopy, Electron ; Middle East Respiratory Syndrome Coronavirus/*genetics/isolation & purification ; RNA, Viral/genetics/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Serum Albumin/analysis

Cytosolic retinoic acid-inducible gene I (RIG-I) is an important innate immune RNA sensor and can induce antiviral cytokines, e.g., interferon-β (IFN-β). Innate immune response to hepatitis B virus (HBV) plays a pivotal role in viral clearance and persistence. However, knowledge of the role that RIG-I plays in HBV infection is limited. The woodchuck is a valuable model for studying HBV infection. To characterize the molecular basis of woodchuck RIG-I (wRIG-I), we analyzed the complete coding sequences (CDSs) of wRIG-I, containing 2778 base pairs that encode 925 amino acids. The deduced wRIG-I protein was 106.847 kD with a theoretical isoelectric point (pI) of 6.07, and contained three important functional structures [caspase activation and recruitment domains (CARDs), DExD/H-box helicases, and a repressor domain (RD)]. In woodchuck fibroblastoma cell line (WH12/6), wRIG-I-targeted small interfering RNA (siRNA) down-regulated RIG-I and its downstrean effector-IFN-β transcripts under RIG-I' ligand, 5'-ppp double stranded RNA (dsRNA) stimulation. We also measured mRNA levels of wRIG-I in different tissues from healthy woodchucks and in the livers from woodchuck hepatitis virus (WHV)-infected woodchucks. The basal expression levels of wRIG-I were abundant in the kidney and liver. Importantly, wRIG-I was significantly up-regulated in acutely infected woodchuck livers, suggesting that RIG-I might be involved in WHV infection. These results may characterize RIG-I in the woodchuck model, providing a strong basis for further study on RIG-I-mediated innate immunity in HBV infection.
Animals ; Cell Line, Tumor ; Cloning, Molecular ; DEAD Box Protein 58 ; antagonists & inhibitors ; genetics ; immunology ; Fibroblasts ; immunology ; pathology ; Gene Expression ; Hepatitis B ; genetics ; immunology ; pathology ; veterinary ; Hepatitis B Virus, Woodchuck ; Immunity, Innate ; Interferon-beta ; genetics ; immunology ; Isoelectric Point ; Kidney ; immunology ; pathology ; virology ; Liver ; immunology ; pathology ; virology ; Marmota ; genetics ; immunology ; virology ; Open Reading Frames ; Protein Domains ; RNA, Double-Stranded ; RNA, Small Interfering ; genetics ; metabolism ; Rodent Diseases ; genetics ; immunology ; pathology ; virology

BK virus-associated nephropathy (BKVAN) is one of the major causes of allograft dysfunction in kidney transplant (KT) patients. We compared BKVAN combined with acute rejection (BKVAN/AR) with BKVAN alone in KT patients. We retrospectively analyzed biopsy-proven BKVAN in KT patients from 2000 to 2011 at Seoul National University Hospital. Among 414 biopsies from 951 patients, biopsy-proven BKVAN was found in 14 patients. Nine patients had BKVAN alone, while 5 patients had both BKVAN and acute cellular rejection. BKVAN in the BKVAN alone group was detected later than in BKVAN/AR group (21.77 vs 6.39 months after transplantation, P=0.03). Serum creatinine at diagnosis was similar (2.09 vs 2.00 mg/dL). Histological grade was more advanced in the BKVAN/AR group (P=0.034). Serum load of BKV, dose of immunosuppressants, and tacrolimus level showed a higher tendency in the BKVAN alone group; however it was not statistically significant. After anti-rejection therapy, immunosuppression was reduced in the BKVAN/AR group. Renal functional deterioration over 1 yr after BKVAN diagnosis was similar between the two groups (P=0.665). These findings suggest that the prognosis of BKVAN/AR after anti-rejection therapy followed by anti-BKV therapy might be similar to that of BKVAN alone after anti-BKV therapy.
Acute Disease ; Adult ; Antiviral Agents/therapeutic use ; BK Virus/*physiology ; Creatinine/blood ; Female ; *Graft Rejection/diagnosis/virology ; Humans ; Immunosuppressive Agents/administration & dosage ; Kidney/*virology ; Kidney Diseases/pathology/surgery/*virology ; *Kidney Transplantation ; Male ; Middle Aged ; Polyomavirus Infections/drug therapy/*etiology/pathology ; Retrospective Studies ; Tacrolimus/administration & dosage ; Time Factors ; Transplantation, Homologous/adverse effects ; Tumor Virus Infections/drug therapy/*etiology/pathology

Hepatitis A virus (HAV) infections occur predominantly in children, and are usually self-limiting. However, 75-95% of the infections in adults are symptomatic (mostly with jaundice), with the illness symptoms usually persisting for a few weeks. Atypical manifestations include relapsing hepatitis, prolonged cholestasis, and complications involving renal injury. Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is a severe, drug-induced hypersensitivity reaction characterized by skin rash, fever, lymph-node enlargement, and internal organ involvement. We describe a 22-year-old male who presented with acute kidney injury and was diagnosed with prolonged cholestatic hepatitis A. The patient also developed DRESS syndrome due to antibiotic and/or antiviral treatment. To our knowledge, this is the first report of histopathologically confirmed DRESS syndrome due to antibiotic and/or antiviral treatment following HAV infection with cholestatic features and renal injury.
Acute Kidney Injury/diagnosis ; Anti-Bacterial Agents/*adverse effects/therapeutic use ; Cefotaxime/adverse effects/therapeutic use ; Cholestasis/complications/*diagnosis ; Cytomegalovirus/genetics ; Cytomegalovirus Infections/drug therapy/virology ; DNA, Viral/analysis ; Eosinophilia/etiology ; Exanthema/*chemically induced/pathology ; Ganciclovir/therapeutic use ; Hepatitis A/complications/*diagnosis/drug therapy ; Humans ; Hydrocortisone/therapeutic use ; Immunoglobulins/therapeutic use ; Male ; Syndrome ; Young Adult

OBJECTIVETo study the clinical and histopathologic features, diagnosis, pathogenesis and therapy of post-transplant lymphoproliferative disorders (PTLD).

METHODSThe clinical and pathologic features of 15 cases of PTLD were retrospectively analyzed by light microscopy, immunohistochemistry and in-situ hybridization, according to the updated 2008 WHO classification of tumors of hematopoietic and lymphoid tissues.

RESULTSAmongst the 15 cases studied, 14 cases had received allogenic hematopoietic stem cell transplantation (AHSCT) and 1 case had received renal transplantation. There were altogether 12 males and 3 females. The male-to-female ratio was 4:1. The mean age was 30.4 years and the median age was 31 years (range from 9 to 60 years). PTLD developed 1.5 to 132 months after transplantation (median 13.0 months). The mean age of the 14 patients with AHSCT was 28.3 years (range from 9 to 45 years) and PTLD developed 1.5 to 19 months after transplantation (mean 4.5 months). Major clinical presentation included fever and lymphadenopathy. Twelve cases involved mainly lymph nodes and the remaining 3 cases involved tonsils, stomach and small intestine, respectively. The histologic types in 4 cases represented early lesions, including plasmacytic hyperplasia (n = 1) and infectious mononucleosis-like PTLD (n = 3). Seven cases were polymorphic PTLD, with 4 cases containing a predominance of large cells. Graft-versus-host disease was also seen in the case of small intestinal involvement. Four cases were monomorphic PTLD, 3 of which were diffuse large B-cell lymphoma, 1 was plasmablastic lymphoma and 1 was a mixture of monomorphic and polymorphic PTLD. Foci of necrosis were seen in 5 cases. The proliferating index of Ki-67 was high. The positive rate of EBV-encoded RNA in AHSCT was 92.9%. The duration of PTLD onset was shorter in EBV-positive cases (range from 1.5 to 7 months) than EBV-negative cases (range from 19 and 132 months). Some cases were treated by reduction of immunosuppression, antiviral agents or anti-CD20 monoclonal antibody Rituximab. The duration of follow-up in 14 patients ranged from 0 to 8 months. Five of the patients died of the disease.

CONCLUSIONSThe diagnosis of PTLD relies on morphologic examination and immunohistochemistry. Most of them are of B-cell origin. EBV plays an important role in the pathogenesis of PTLD. The duration of disease onset is shorter in EBV-positive cases. PTLD in AHSCT cases occurs in younger age group, with shorter duration of onset, as compared to solid organ transplantation. The prognosis of PTLD is poor. The modalities of treatment include reduction of immunosuppression, antiviral agents or anti-CD20 monoclonal antibody Rituximab.

ADP-ribosyl Cyclase 1 ; metabolism ; Adolescent ; Adult ; Antibodies, Monoclonal, Murine-Derived ; therapeutic use ; Antigens, CD20 ; metabolism ; Antineoplastic Agents ; therapeutic use ; Child ; Epstein-Barr Virus Infections ; Female ; Follow-Up Studies ; Hematopoietic Stem Cell Transplantation ; adverse effects ; Herpesvirus 4, Human ; isolation & purification ; Humans ; Immunosuppressive Agents ; therapeutic use ; Ki-1 Antigen ; metabolism ; Kidney Transplantation ; adverse effects ; Leukemia ; therapy ; Lymphoma, Large B-Cell, Diffuse ; drug therapy ; etiology ; pathology ; virology ; Lymphoproliferative Disorders ; drug therapy ; etiology ; pathology ; virology ; Male ; Middle Aged ; RNA, Viral ; metabolism ; Retrospective Studies ; Rituximab ; Young Adult

In order to find antiviral compounds with novel structures, geldanamycin and lamivudine with different antiviral mechanisms were conjunctively synthesized to acquire a new compound TC-GM, and the antiviral activity of TC-GM was measured. The antiviral activity against HIV-1 was examined by p24 antigen ELISA kit. The activity against HBV was examined by dotblot. The activity against HSV and CoxB virus was examined by CPE. TC-GM exhibited broad-spectrum antiviral activities similarly like geldanamycin. TC-GM inhibited the replication of different viruses, including HIV-1, HBV, HSV 1 and 2, CoxB6. TC-GM showed more potent inhibitory activity against HIV-1 and HBV than other detected virus.
Animals ; Anti-HIV Agents ; chemical synthesis ; chemistry ; pharmacology ; Antiviral Agents ; chemical synthesis ; chemistry ; pharmacology ; Benzoquinones ; chemical synthesis ; chemistry ; pharmacology ; Cell Line, Tumor ; Cercopithecus aethiops ; Enterovirus B, Human ; drug effects ; physiology ; HIV-1 ; drug effects ; physiology ; Hep G2 Cells ; Hepatitis B virus ; drug effects ; physiology ; Herpesvirus 1, Human ; drug effects ; physiology ; Herpesvirus 2, Human ; drug effects ; physiology ; Humans ; Lactams, Macrocyclic ; chemical synthesis ; chemistry ; pharmacology ; Lamivudine ; chemical synthesis ; chemistry ; pharmacology ; Madin Darby Canine Kidney Cells ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; pathology ; virology ; Vero Cells ; Virus Replication ; drug effects

Adenovirus Infections, Human ; pathology ; virology ; Glomerulonephritis, Membranous ; pathology ; virology ; HIV Infections ; pathology ; virology ; Hepatitis B ; pathology ; virology ; Hepatitis C ; pathology ; virology ; Herpes Zoster ; pathology ; virology ; Herpesvirus 3, Human ; isolation & purification ; Humans ; Kidney ; pathology ; virology ; Kidney Diseases ; pathology ; virology ; Nephritis, Interstitial ; pathology ; virology ; Parvoviridae Infections ; pathology ; virology ; Parvovirus B19, Human ; isolation & purification

In order to explore the morphological changes of Bovine Kidney (MDBK) cells induced by foot-and-mouth disease virus (FMDV) L protease, we induced the expression of FMDV L protease in bovine kidney cells (MDBK) artificially. All work is carried out on the basis of a stable MDBK cell line inducibly expresses the Lab gene under the control of tetracycline. We use cell morphology, Hoechst 33258 staining, AO-EB staining, and DNA Ladder abstraction to research the morphological changes of MDBK cells. 24 hours after FMDV L protease were induced and expressed in MDBK cells, cells shown the diminish of cell size, nuclear enrichment and the appearance of transparency circle under the light microscope. Apoptosis characteristics of nuclear condensation, fragmentation, accompanied by apoptotic bodies formation (Hoechst 33258 staining). 36 hours after the expression, nuclear staining of early lesions showed bright green plaque or debris-like dense, and advanced lesions showed Orange and dense plaques (AO-EB staining). 48 hours after the expression, DNA gel electrophoresis showed visible DNA ladder. Results indicate that FMDV L protease can induce apoptosis of MDBK and apoptosis plays an important role in the cytopathogenicity effect of FMDV.
Animals ; Cattle ; Cell Line ; Endopeptidases ; biosynthesis ; genetics ; Foot-and-Mouth Disease Virus ; pathogenicity ; Kidney ; cytology ; pathology ; virology ; Transfection

BK virus (BKV) is a subtype of papovaviridae. The latent and asymptomatic infection of BKV is common among healthy people. The incidence of BKV re-activation in renal transplant recipients ranges 10%-68%. About 1%-7% of renal transplant recipients will suffer from BKV-associated nephropathy (BKVAN), and half of them will experience graft failure. This paper summarizes the re-activation mechanism of BKV as well as the risk factors, pathology, diagnosis, and treatment of BKVAN.
BK Virus ; physiology ; Humans ; Kidney ; pathology ; virology ; Kidney Transplantation ; Polyomavirus Infections ; diagnosis ; pathology ; therapy ; Postoperative Complications ; diagnosis ; pathology ; therapy ; virology ; Risk Factors ; Tumor Virus Infections ; diagnosis ; pathology ; therapy ; Virus Activation

OBJECTIVEHepatitis B virus-associated membranous nephropathy (HBV-MN) is a disease characterized by podocytopathy. Podocyte is a terminally differentiated cell with limited capability of proliferation. Thus, damage of podocyte might result in decreased cell number, and then lead to the development of marked proteinuria and glomerulosclerosis. The present study aimed to investigate the changes of glomerular podocyte number in the children with hepatitis B virus-associated membranous nephropathy (HBV-MN), and their significance in the pathogenesis of HBV-MN.

METHODSPodocytes were identified through specific immunohistological staining of Wilms tumor gene protein 1 (WT1), a characteristic marker for podocyte nuclei, and podocyte numerical density (Nv), mean glomerular tuft volume (V) and the podocyte number per glomerulus (Npodo) were estimated through Weibel-Gomez method in 19 children with biopsy-proven HBV-MN and 8 children with thin basement membrane disease (control group), and analyses were made for possible correlation with clinical, serological and pathological data.

RESULTSAmong the 19 cases with HBV-MN, 3 showed microvillus-like foot process of podocytes, granular degeneration of podocyte were found in 4 cases, vacuolization in 1 case and podocyte detachment in 2 cases. Nv and Npodo were significantly decreased in children with HBV-MN compared with control group (t = 12.851, P = 0.0002 and t = 6.433, P = 0.0002, respectively). Moreover, the number of podocytes decreased more significantly in patients with stronger HBsAg deposition (> ++) than those with weak HBsAg deposition (< or = ++), P = 0.004, but no significant difference was found between patients with phase III or IV of HBV-MN and those with phase Ior II in podocyte number per glomerulus (P = 0.5262) and podocyte numerical density (P = 0.3564). Podocyte numerical density decreased more significantly in patients with massive proteinuria (> or = 2 g/24 h) than those with moderate proteinuria (< 2 g/24 h), P = 0.0488. The numbers of podocyte correlated significantly with serum levels of C(3) (r = 0.548, P = 0.028), but did not correlate with serum levels of albumin (r = -0.037, P = 0.891).

CONCLUSIONAll patients with HBV-MN showed podocyte damage and decreased number per glomerulus, which may play an important role in the pathogenesis of HBV-MN in children.

Cell Count ; Child ; Glomerulonephritis ; pathology ; Glomerulonephritis, Membranous ; complications ; virology ; Hepatitis B ; complications ; pathology ; Hepatitis B virus ; Humans ; Kidney Diseases ; pathology ; Kidney Glomerulus ; pathology ; Podocytes ; pathology ; Proteinuria ; pathology