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PubMed1981

Acute viral encephalitis: its diagnosis and outcome.

Sixty patients with acute viral encephalitis admitted to The London Hospital in the last fifteen years have been reviewed. These consisted of 12 patients with known viral infection, 29 patients with acute viral infection of undetermined type, and 19 patients in whom an encephalitic illness followed a viral infection (post-infection encephalitis). The patients with primary viral encephalitis presented with an inflammatory brain disorder, including headaches and fever, and developed focal or diffuse neurological signs. Patients with post-infection encephalitis, usually following a 'flu'-like illness, presented with an acute neurological disturbance. The results of investigations, including virological studies, CSF examination, electroencephalography and neuroradiology, are described. Biopsy or autopsy material was available in 11 patients and these pathological findings supported the clinical classification of these patients. The mortality was highest in patients with herpes simplex virus encephalitis and lowest in patients with post-infection encephalitis. A considerable morbidity was found, not only in patients with primary viral encephalitis, but also in patients with encephalitis of unknown aetiology and post-infection encephalitis.

Acute Disease↗
PubMed1995

Nucleotide sequence of the NS5 gene of Banzi virus: comparison with other flaviviruses.

Banzi is a mosquito borne flavivirus which belongs to the Uganda S serocomplex. No nucleotide sequence data have previously been reported from any virus of this serocomplex. We have determined the nucleotide sequence of the NS5 gene from Banzi virus and the predicted amino acid sequence was elucidated. Previously identified conserved RNA polymerase, methyltransferase and flavivirus NS5 amino acid motifs were present in the Banzi virus NS5 protein. These data add to the evidence for the functional importance of the regions. The encoded amino acid sequence was compared with the predicted amino acid sequence of other flavivirus NS5 proteins. Analysis of these sequences suggested that Banzi virus is most closely related to the mosquito-borne flaviviruses and, in particular, yellow fever virus. This pattern of similarity is in accordance with the previously suggested serological classification of flaviviruses.

Amino Acid Sequence↗
PubMedDate not supplied

[Interferon--properties and action].

The role played by interferon in human organism is described, with particular reference to its immunomodulatory effects. The classification of interferons, and the mode of its synthesis in cells infected by viruses are presented. The molecular bases of interferon action as a protein inhibiting virus development and the role of gamma interferon in human immunity are discussed.

Adjuvants, Immunologic↗
PubMed1992

Pathology of malignant lymphomas.

Although the subject is now seldom formally addressed, much of the pathologic research into malignant lymphoma is still tacitly directed at developing a rational and reproducible classification. Pure morphology, while remaining of critical importance in the diagnosis of malignant lymphomas, has been exhausted as a means of understanding the biology of these tumors, which must be the eventual basis of a firm, enduring and clinically relevant classification. Thus, histopathologists have turned first to immunohistochemistry and now to molecular genetics to make sense of their morphologic observations. Correlation of various genetic (including oncogenetic) rearrangements with morphology has preoccupied pathologists this past year and has led to important advances in the understanding of B- and T-cell lymphomas. Lymphomas occurring in a setting of immunodeficiency, whether therapeutically induced or acquired, have received special attention, and the possible role of the Epstein-Barr virus in their pathogenesis has induced pathologists to develop exciting in situ molecular hybridization techniques for its identification in tissues. The certainties underlying the diagnosis and classification of Hodgkin's disease (in which Epstein-Barr virus also appears to play a role), formally the only truly secure area for pathologists, have been disturbed, and the borderline between Hodgkin's disease and non-Hodgkin's lymphoma is now seriously blurred. The lymphoma pot has been well and truly stirred; we must now wait to see what the new sediment offers.

Humans↗
PubMed2006

Functional genomic analysis of herpes simplex virus type 1 counteraction of the host innate response.

Herpes simplex virus type 1 (HSV-1) mutants lacking the ICP34.5 gene are severely attenuated in mouse models and have a significant growth defect in confluent mouse embryo fibroblasts. Previously, ICP34.5 was demonstrated to have a crucial role in evading the innate immune response to infection by mediating the dephosphorylation of eIF2alpha, a translation initiation factor phosphorylated by PKR during the antiviral response. To further understand the role of ICP34.5 in evasion of the antiviral response, we used transcriptional profiling to examine host cell gene expression in both wild-type and ICP34.5-null virus-infected mouse embryo fibroblasts over a time course of infection. Our study revealed that cells responded to infection within 3 h through PKR-dependent eIF2alpha phosphorylation and that the majority of up-regulated genes at 3 h postinfection were involved in the antiviral response. HSV-1 counters this response through early expression of ICP34.5 and dephosphorylation of eIF2alpha. By 12 h postinfection, the differences between the number and functional classification of genes differentially up- and down-regulated between wild-type and ICP34.5-null virus-infected cells were maximal. Specifically, in wild-type virus-infected cells, the majority of changed genes were involved in metabolic and biosynthetic processes, while in ICP34.5-null virus-infected cells, mostly antiviral genes were up-regulated. Further, ICP34.5-null virus-infected cells produced greater amounts of beta interferon than wild-type virus-infected cells. These results indicate that ICP34.5 expression and function at early times postinfection have a pivotal role in the ability of HSV-1 to gain control of the host cell and maintain an environment for successful viral replication.

Animals↗
PubMed1998

[GB virus-C/hepatitis G virus--discovery, epidemiology, diagnosis and clinical relevance].

Recently, two isolates of a new virus, designated GB virus C (GBV-C) and hepatitis G virus (HGV) were identified. Genomic organization place them in the family Flaviviridae, which includes HCV. A classification of GBV-C/HGV strains into at least three genotypes (West Africa, Europe/North America, Asia) has been proposed. GBV-C/HGV has a positive-stranded, linear RNA genome possessing a large open reading frame that encodes a single large polyprotein. As a possible genomic defect no core protein has yet been identified in GBV-C/HGV isolates. Whether GBV-C/HGV can be classified as a hepatotropic virus with replication in the liver is under discussion. The prevalence in the general population is high (2%). GBV-C/HGV is transmitted parenterally e.g., by transfusion of blood and blood products. Furthermore, cases of vertical and horizontal transmission are reported. Detection of GBV-C/HGV infection is exclusively possible by reverse transcription polymerase chain reaction (RT PCR). E2-specific antibodies are associated with loss of detectable GBV-C/HGV RNA and appear to indicate recovery from GBV-C/HGV infection. An acute icteric state with transient elevation of aminotransferases in association with GBV-C/HGV infection may exist. These cases are rare and approximately only 0.3% of persons with acute viral hepatitis are infected with GBV-C/HGV alone. Whether GBV-C/HGV is a cause of fulminant hepatic failure has not yet been proven. Persistent viremia of the GBV-C/HGV infection is frequent but is not related to chronic liver disease. Since no other chronic diseases associated with GBV-C/HGV infection could yet be identified, chronic GBV-C/HGV infections appear to be without clinical significance. GBV-C/HGV and hepatitis B or C virus (HBV, HCV) coinfection seem not to interfere with the outcome of HBV-respective HCV-related liver disease. The cause of the majority of cases with non-A-E viral hepatitis remains unknown and other yet undiscovered hepatic viruses must exist.

Cross-Sectional Studies↗
PubMed1993

Molecular diversity of the Lyssavirus genus.

The sequence of 5568 nucleotides of the 3' moiety of the Mokola virus genome (serotype 3 of lyssaviruses) encompassing the nucleoprotein (N), phosphoprotein, matrix protein, and glycoprotein genes is presented and compared to that of the vaccinal strains of serotype 1. It allowed us to determine consensus sequences derived from the transcriptional start/stop signals and the order of protein conservation (nucleoprotein > matrix protein > phosphoprotein) in lyssaviruses. The sequences of the N gene of a fox rabies virus isolate from France (serotype 1), Lagos bat virus (serotype 2), Duvenhage virus (serotype 4), two European bat lyssaviruses (EBL) subtype 1, and two EBL subtype 2 were also determined to study the genetic diversity throughout the whole Lyssavirus genus and reinvestigate the classification of this genus. Six clearly distinct genotypes can be distinguished according to their percentage of amino acid similarity. Genotypes 2 (Lagos bat virus) and 3 (Mokola virus) are the most phylogenetically distant from the vaccinal and classical rabies viruses of genotype 1. Genotypes 4 (Duvenhage virus) and 5 (EBL1) are closely related to each other. Genotype 6 is represented by EBL2. Compared to the N proteins of the four principal serotypes of the Vesiculovirus genus (vesicular stomatitis virus serotype New Jersey and serotype Indiana, Chandipura virus, and Piry virus), the N gene of lyssaviruses exhibits a lower genetic variability.

Amino Acid Sequence↗
PubMed1995

[Mixed cryoglobulinemia and the hepatitis C virus].

Mixed cryoglobulinemia is a cryoprecipitable immune-complex mediated disease, in which cryoglobulins are type II and III of the immunochemical classification of Brouet. Essential mixed cryoglobulinemia, in opposition to secondary, is characterized by the absence of well-defined underlying disease and clinically it shows the classical triad of Meltzer and Franklin. Several reports point to the frequent, through various, liver involvement in essential-defined mixed cryoglobulinemia. Particularly, the clinical and biological evidence of liver disease is commonly soft, in spite of the common bioptic evidence of persistent or chronic active hepatitis. The problem about which comes first in this association had been widely investigated, including the possible pathogenetic role of hepatotropic viruses. Initially some studies focused attention on hepatitis B virus, but now its importance is de-emphasized because of critical epidemiological review, results of HBV-DNA in cryoprecipitates, electron microscopy data. The recent opportunity of diagnostic tests for hepatitis C virus gave proof of its great importance in apparently essential mixed cryoglobulinemia. In fact, many researches have found a variously high prevalence of anti HCV antibodies and HCV-RNA in serum and cryoprecipitates, with selective concentration in the latter. Alpha interferon treatment has been suggested as first choice drug in the management of HCV related cryoglobulinemia. The mechanism is postulated to be primarily due to its antiviral activity. Up to date optimal dose and treatment period needs to be established.

Cryoglobulinemia↗
PubMed2005

High prevalence of viral genomes and multiple viral infections in the myocardium of adults with "idiopathic" left ventricular dysfunction.

BACKGROUND: For a long time, enteroviruses have been considered to be the most common cause of acute viral myocarditis (MC), with possible transition from MC to dilated cardiomyopathy (DCM). Recent investigations have shown, however, that other viruses are also frequently encountered in MC patients, suggesting that persistence of various virus species may play a pathogenic role in the transition from MC to DCM. The purpose of this study was to screen endomyocardial biopsies (EMBs) from patients with "idiopathic" DCM for the presence of viral genomes by using polymerase chain reaction (PCR) to assess the frequency of cardiac viral infections that may be involved in the pathogenesis of the disease. METHODS AND RESULTS: EMBs were obtained for PCR analysis from 245 consecutive patients (median left ventricular ejection fraction, 35.0%; range, 9% to 59%). PCR and reverse transcription-PCR were performed to detect the genomic sequences of enterovirus (EV), adenovirus (ADV), human cytomegalovirus (HCMV), herpes simplex virus, Epstein-Barr virus (EBV), human herpesvirus 6 (HHV-6), parvovirus B19 (PVB19), and influenza A and B viruses. Myocardial inflammation was assessed by histological and immunohistological analyses. Viral genomes could be amplified from EMBs of 165 (67.4%) of the 245 DCM patients: EV=23 (9.4%), ADV=4 (1.6%), PVB19=126 (51.4%), HHV-6=53 (21.6%), EBV=5 (2.0%), HCMV=2 (0.8%), including n=45 cases (27.3%) with multiple infections. Active or borderline myocarditis according to the Dallas classification did not exist in any case. Lymphocyte and macrophage infiltrates were not significantly different in virus-positive versus virus-negative patients. CONCLUSIONS: Viral genomes were frequently detected in EMBs of patients with systolic left ventricular dysfunction. Our data suggest that myocardial persistence of various viruses, often presenting as multiple infections, may play a role in the pathogenesis of DCM far more frequently than suspected so far.

Adult↗
PubMed1992

[Serologic response to some herpesviruses in a group of HIV infected patients].

The titres of antibodies to the herpes simplex virus, cytomegalovirus, and the antigen of viral envelope of Epstein-Barr virus were determined in serum samples from patients infected by the human immunodeficiency virus (HIV) who belonged to groups II (n = 26) and IV (n = 32) according to the present Classification System of HIV infection, as well as in a group of blood donors (n = 52). The geometrical average titres obtained in the different agents were very high in patients having HIV infection with respect to the geometrical average titres observed in blood donors. Patients from group II had titres to the antigen of viral envelope of the Epstein-Barr virus significantly higher than blood donors. Levels of antibodies to these agents in patients from group IV were higher than levels obtained in blood donors. Differences regarding levels of the antigen of viral envelope of the Epstein-Barr virus were highly significant. These results suggest the possible relevance of the Epstein-Barr virus infection in the natural history of AIDS.

Antibodies, Viral↗
PubMed2000

Concentrations of organochlorines related to titers to Epstein-Barr virus early antigen IgG as risk factors for hairy cell leukemia.

Hairy cell leukemia (HCL) is a rare chronic B-cell malignancy that, according to modern classifications, is a subgroup of non-Hodgkin lymphomas (NHLs). A rapid increase in incidence of NHL has been reported in many countries. The reasons for this increase are largely unknown, but exposure to organochlorines has been suggested as a risk factor. Epstein-Barr virus is a human herpesvirus that has been associated with certain subgroups of NHL. In this study, we measured lipid adjusted blood concentrations (in nanogram per gram) of 36 congeners of polychlorinated biphenyls (PCBs), p, p'-dichlorodiphenyldichloroethylene (p,p'-DDE), hexachlorobenzene (HCB), and four subgroups of chlordanes (trans-nonachlor, cis-nonachlor, MC6, and oxychlordane) in incident cases of HCL and controls from the general population. We obtained results on organochlorines and antibodies for 54 cases and 54 controls. Titers of antibodies to the Epstein-Barr early antigen and Epstein-Barr nuclear antigen, measured as P107, were correlated to concentrations of organochlorines to evaluate the possibility of an interaction between these factors in the pathogenesis of HCL. We found no significant difference in lipid-adjusted blood concentrations of total PCBs, p,p'-DDE, HCB, or the sum of the chlordanes between cases and controls. Titers of antibodies to Epstein-Barr early antigen IgG [Greater and equal to] 40 were correlated to an increased risk for HCL. This risk was further increased in those with a level above the median value of p,p'-DDE, HCB, or the sum of the chlordanes, suggesting an interaction between Epstein-Barr virus and a higher concentration of these chemicals. We also found increased risk for the sum of immunotoxic PCB group.

Antibodies, Viral↗
PubMed2001

Characterization of ATI, TK and IFN-alpha/betaR genes in the genome of the BeAn 58058 virus, a naturally attenuated wild Orthopoxvirus.

The lack of knowledge about the natural host of Vaccinia virus (VV) along with the description of human infections caused by poxviruses after smallpox eradication has increased the need to characterize poxviruses isolated from the wild. Moreover, in the past years poxviruses have been widely studied as potential vaccination tools, with the discovery of several genes implicated in the evasion of the host immune response involved in virus pathogenesis. Among them, an Interferon (IFN)-binding protein was identified in the supernatant of VV strain WR infected cells coded by the B18R gene. It was shown that many other Orthopoxviruses also encode and express this soluble receptor although some VV strains such as Lister and modified Ankara, which were less reactogenic vaccines, do not. The BeAn 58058 virus (BAV) has been recently characterized and proposed to be an Orthopoxvirus. BAV was also shown to be less virulent in animal models than VV Lister. Here we report the identification of an IFN-alpha/betaR gene in the BAV genome with 99% of sequence identity with the VVWR B18R gene. The identified gene encodes a B18R-like IFN binding protein as demonstrated by its capacity to inhibit the IFN-mediated protection of VERO cells against EMC virus. In order to better characterize the virus we have searched for the A type inclusion body (ATI) gene currently used in the classification of Orthopoxviruses but did not detect it in the BAV genome. We have also sequenced the BAV thymidine kinase (TK) gene, a poxvirus-conserved gene, which, as expected, showed high homology with the TK gene of other poxviruses. Phylogenetic trees were constructed based on sequences of the IFN-alpha/betaR and TK genes from several poxviruses and in both cases BAV was placed in the same cluster as other VV strains. These observations strengthened the hypothesis that this virus is a variant of the VV vaccine used in Brazil. However the explanation for the BAV lack of virulence remains to be discovered.

Amino Acid Sequence↗
PubMed2005

Daphne mosaic virus (DapMV), a new potyvirus from Daphne mezereum in the Czech Republic.

Daphne shrubs with light green rings and mosaic on leaves contained flexuous filamentous virions (696 x 13 nm) and cylindrical inclusions typical of the subdivision III of Edwardson's classification for inclusions induced by members of the family Potyviridae. Decoration tests using antisera to 67 potyviruses revealed distant serological relations among chilli veinal mottle virus, Colombian datura virus, papaya ringspot virus, tobacco vein mottling virus and yam mosaic virus. The 3' terminal region of the virus genome was amplified by RT-PCR using primers specific for cloned and sequenced members of the family Potyviridae. The most similar sequences in the GenBank were those of isolates of wild potato mosaic virus (WPMV) and yam mild mosaic virus (YMMV), originating from Peru and Guadeloupe, respectively. The new sequence had 63.2% and 61.9% nucleotide identity to WPMV and YMMV in the coat protein gene. The results suggest that the Czech isolate from daphne should be regarded as a new member of the genus Potyvirus. The name daphne mosaic virus (DapMV) is suggested for this virus.

Capsid Proteins↗
PubMed2005

Diagnosis coding in The Danish National Patient Registry for respiratory syncytial virus infections.

This national registry-based epidemiological study aimed to evaluate the usefulness of the Danish National Patient Registry (DNPR) as a tool for epidemiological studies of respiratory syncytial virus (RSV) hospitalizations. Information on RSV diagnoses in records of hospitalizations among inpatients tested for RSV in Denmark from January 1996 to May 2003 in the DNPR was validated against the RSV test result in records from the 18 laboratories testing for RSV among hospitalized patients in Denmark. Of 16,733 RSV-positive samples representing a total of 14,898 hospitalizations in the DNPR, 68% (10,111) had been registered in the DNPR with 1 or more RSV diagnoses. Age influenced the odds ratio (OR) of being coded with a RSV diagnosis among patients with a RSV positive test, hence 73% of infants compared to 57% of patients beyond infancy had been registered in the DNPR with 1 or more RSV diagnoses. The OR of being coded with a RSV diagnosis among patients with an RSV positive test was increased over the study period and was also increased by increasing length of hospitalization and by the presence of secondary diagnoses. The OR was decreased by the presence of asthma and other chronic conditions in the patients. The OR was furthermore influenced by RSV seasonality and by hospital. Taking into account a loss of 27% of RSV hospitalizations, DNPR can be used for epidemiological studies of RSV among infants in Denmark.

Databases, Factual↗
PubMed2000

Lymphomatous features of aggressive NK cell leukaemia/lymphoma with massive necrosis, haemophagocytosis and EB virus infection.

AIMS: Aggressive natural killer (NK) cell leukaemia will be categorized as a distinct entity in the new WHO classification of malignant lymphomas. However, its non-leukaemic features remain unclear. We therefore investigated the morphological and immunophenotypic features of this lymphoma. METHODS AND RESULTS: Four cases with aggressive NK cell lymphoma were morphologically and immunohistochemically studied. All cases followed an aggressive course with death occurring within about 3 months of initial presentation. In these cases, the neoplastic cells disseminated throughout systemic lymph nodes and invaded various tissues and organs. The lymphoma cells were large cells showing nuclear irregularity and a pattern of sinusoidal invasion in lymph nodes. Apoptosis and coagulation necrosis were both frequently observed. Haemophagocytosis was observed in all cases. Neoplastic cells in paraffin-embedded tissue specimens from these patients had CD3(CD3epsilon)+ CD56(123C3)+ granzyme+ TIA-1+ EBERT+ CD43(MT1)- CD45RO(UCHL-1)- CD57(Leu7)- CD20(L26)- phenotypes. In the two cases where tissue was available for immunohistochemical study in frozen sections, neoplastic cells showed CD56(Leu19)+ perforin+ Fas ligand(FasL)+ CD2(Leu5b)- CD3(Leu4)- CD4(Leu3)- CD5(Leu1)- CD7(Leu9)- CD8(Leu2)- betaF1- TCRdelta1- phenotypes. CD16(Leu11b) was positive in one case. CONCLUSIONS: : Natural killer cell lymphomas appear to represent a non-leukaemic counterpart of aggressive natural killer cell leukaemia, a relationship similar to that in adult T-cell leukaemia/lymphoma. Awareness and diagnosis of this aggressive lymphoma is important because of its fulminant course.

Adult↗