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Myocardial biopsy based classification and treatment in patients with dilated cardiomyopathy.

BACKGROUND: We investigated whether myocardial biopsy analysis for inflammation and viruses correlates with outcome in dilated cardiomyopathy. METHODS: Myocardial biopsies of 82 patients were analyzed for HLAI, HLAII, CD54, CD2, CD68 and entero-/adenovirus. Ejection fraction was determined by left ventriculography. NYHA classification, electrocardiogram (ECG) and echocardiography were analyzed at first admission and for follow up. Patients were attributed to three groups: (A) no inflammation/no virus (B) inflammation/no virus (C) virus with/without inflammation. Patients not responding to conventional treatment of heart failure received interferon beta1b (group C) or prednisolone (group B). Median follow up was 7 months (group A), 11 months (group B) and 14.5 months (group C). RESULTS: Thirty nine patients (48%) belonged to group A, 33 patients (40%) to group B, 10 patients (12%) to group C. Only enterovirus was detected. Ejection fraction at admission was worse for group B compared to group A (p=0.003). Groups A and B improved for echocardiography and NYHA (p< or =0.001). Group C improved for echocardiography only (p=0.031). Group B showed a better outcome for echocardiography (p=0.014) and NYHA (p=0.023) than group A. CONCLUSIONS: Inflammatory cardiomyopathy shows the best outcome. Antiinflammatory or antiviral treatment may be an option in patients not responding to conventional therapy.

Adjuvants, Immunologic↗

An emergent poxvirus from humans and cattle in Rio de Janeiro State: Cantagalo virus may derive from Brazilian smallpox vaccine.

The biological properties of poxvirus isolates from skin lesions on dairy cows and milkers during recent exanthem episodes in Cantagalo County, Rio de Janeiro State, Brazil, were more like vaccinia virus (VV) than cowpox virus. PCR amplification of the hemagglutinin (HA) gene substantiated the isolate classification as an Old World orthopoxvirus, and alignment of the HA sequences with those of other orthopoxviruses indicated that all the isolates represented a single strain of VV, which we have designated Cantagalo virus (CTGV). HA sequences of the Brazilian smallpox vaccine strain (VV-IOC), used over 20 years ago, and CTGV showed 98.2% identity; phylogeny inference of CTGV, VV-IOC, and 12 VV strains placed VV-IOC and CTGV together in a distinct clade. Viral DNA restriction patterns and protein profiles showed a few differences between VV-IOC and CTGV. Together, the data suggested that CTGV may have derived from VV-IOC by persisting in an indigenous animal(s), accumulating polymorphisms, and now emerging in cattle and milkers as CTGV. CTGV may represent the first case of long-term persistence of vaccinia in the New World.

Amino Acid Sequence↗

Human immunodeficiency virus (HIV) infection codes and new codes for Kaposi's sarcoma.

These addenda for Volumes 1 and 2 of the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM), are reported by the World Health Organization Collaborating Center for Classification of Diseases for North America at the National Center for Health Statistics. These addenda replace the addendum containing codes for human immunodeficiency virus (HIV) infection (042.0-044.9) that were effective January 1, 1988. These addenda will be effective October 1, 1991, and are the second revision of these codes for the classification of HIV infection. These addenda incorporate minor changes in content of the classification reflecting new scientific knowledge. The structure of the classification, the codes within the classification, and the manner in which the codes may be used remain unchanged. These changes are effective only for morbidity purposes; the cause-of-death codes are unchanged.

AIDS-Related Complex↗

Serological methods in the diagnosis of bluetongue.

The viral antibodies in the serum of cattle, sheep and deer are not detectable in the ordinary direct CF test. We have shown that the so-called "non complement-fixing" viral antibodies in the serum of these animal species can be demonstrated by the MDCF test. The MDCF test, as well as the micro AGP test, are group reactive, with all BT isolates studied. However, it is possible with these tests to differentiate antigenically BT virus from EHD virus. The FAT was also useful in differentiating BT virus grown in TC cells from the EHD virus. In the PRN test, all the BT virus isolates studied cross reacted and although quantitative differences were frequently observed, no obvious antigenic classification was possible with the antiserums used in this work. Reactions between the BT viral isolates and the EHD virus were all within the limits of what is presently considered to be non-specific inhibition.

Animals↗

Historical background and classification of caliciviruses and astroviruses.

Infections caused by caliciviruses, i.e., vesicular exanthema virus of swine were recognised as a major cause of economic loss in the 1930s. However, it was not until the application of electronmicroscopy in the 1970s that caliciviruses and astroviruses were recognised and proven to be a cause of diarrhoea and vomiting. The following review briefly describes the steps which have led to the development of diagnostic tests and enabled the characterization of several members of the Caliciviridae and Astroviridae. In the past five years this has culminated in the sequencing of their genomes and the expression of viral proteins. This in turn has led to the development of improved diagnostic tests e.g., RT-PCR and enzyme immunoassays, and may pave the way towards producing effective vaccines in the future.

Animals↗

The basis of arbovirus classification.

The biologically defined set of arboviruses contains well over 300 separate viruses which have been subdivided into some 40 serological groups on the basis of antigenic cross-reactivity. More than three quarters of all arboviruses can now bw placed into one of the following five major taxonomic genera based upon the fundamental properties of the virion: alphavirus, flavivirus, orbivirus, rhadovirus, bunyavirus. There are 20 alphaviruses, representing serological Group A, and 57 flaviviruses in serological Group B; these two genera fall into the familty Togaviridae. The 40 orbiviruses, in the family Reoviridae, include some 8 serological groups, and the 8 rhabdoviruses, in the family Rhabdoviridae include another 3 groups. About 160 bunyaviruses, family Bunyaviridae, are divisible into 20 serological groups, 10 of which show intra-group cross-reactions in the Bunyamwera supergroup. One arbovirus contains DNA, namely African swine fever virus; this is classified as an Iridovirus, or icosahedral cytoplasmic deoxyvirus. Nodamura virus, which has been classified as a picornavirus, must be reclassified on the evidence that it possesses a divided genome. A number of arboviruses remain unclassified in taxonomic terms. The absence of arbovirus representatives in several major genera, such as the adenoviruses and the myxoviruses is of no interest.

Arboviruses↗

Genetic analysis of large-sized RNA 2 species of a TCM-like tobacco rattle virus source from spinach.

RNA 2 of a tobacco rattle virus isolate from spinach (TRV SP) resembles that of a recently described isolate from onion (TRV ON), but its ORF 3 is much larger. Naturally infected spinach apparently contains a second TRV SP RNA 2 species with a partially deleted ORF 3 and an RNA 1-like 3'-end which consists of c. 1500 nts and thus is much longer than in any other tobravirus RNA 2 sequenced so far. RNAs 2 of TRV SP and ON are closely related to that of TRV TCM from tulip, but besides the additional ORF 3 they have longer 5'-UTRs with two GCAUA motifs and different coat protein C-termini. The high percentage of amino acid sequence identity in the coat proteins of the TCM-like tobraviruses suggests that they may be considered as strains of a distinct virus species. Possible pitfalls in the use of serology in tobravirus classification are discussed.

5' Untranslated Regions↗

Biochemical and biophysical analysis of heptad repeat regions from the fusion protein of Menangle virus, a newly emergent paramyxovirus.

Menangle virus is a novel paramyxovirus isolated in Australia in 1997, but its classification position has not yet been finally settled. Here by using a computational program, LearnCoil-VMF, we determined the heptad repeat (HR) regions (HR1 and HR2) of Menangle virus F protein. Subsequently the HR1 and HR2 peptides were expressed as a single chain (named 2-Helix) connected by a six amino-acid linker as a GST fusion protein with an E. coli in vitro expression system. The GST-removed purified 2-Helix protein could form a stable trimer in vitro judging by gel-filtration and chemical cross-linking. CD spectra showed that the 2-Helix protein had a high percentage of alpha-helix and was very thermo-stable. Crystals of the 2-Helix protein preparations have been obtained in many conditions with hanging-drop diffusion method. These results indicated that Menangle virus has the common features of the fusion protein for other paramyxoviruses and should adopt a similar fusion mechanism to other members. As the HR regions of Menangle virus F protein could form stable six-helix bundle coiled coil structure, they should be used as drug target for the design of fusion inhibitors, as successfully used for other parmyxoviruses. This is especially relevant to such a newly emergent virus with zoonotic potentials.

Amino Acid Sequence↗

Lymphomas of the oral soft tissues are not preferentially associated with latent or replicative Epstein-Barr virus.

OBJECTIVES: Epstein-Barr virus is periodically shed in the saliva of persons infected by the virus. Epstein-Barr virus has been implicated in the pathogenesis of certain subtypes of lymphoma, particularly high-grade lymphomas. Because high-grade subtypes represent the majority of lymphomas that arise in oral soft tissues, we hypothesized that Epstein-Barr virus might be preferentially associated with oral lymphomas. STUDY DESIGN: A series of 34 oral lymphomas were diagnosed according to the revised European-American classification scheme. They were examined for the presence of latent Epstein-Barr virus by EBER1 in situ hybridization and for expression of the Epstein-Barr virus replicative protein, BZLF1, by immunohistochemistry. RESULTS: Epstein-Barr virus EBER1 transcripts were detected in 11 of 31 oral lymphomas including 7 of 10 AIDS-related lymphomas and only 4 of 21 lymphomas that occurred in nonimmunocompromised persons. The Epstein-Barr virus-containing lymphomas were all high-grade histologic subtypes, that is, diffuse large cell, immunoblastic, or Burkitt's lymphomas. In contrast, Epstein-Barr virus was not detected in any of five low-grade oral lymphomas. In the single case of T-cell lymphoma in this study, EBER1 was expressed in the tumor cells. A switch from viral latency to replication, as measured by EBV BZLF1 expression, was identified in rare lymphoma cells in only four cases. This rate of viral replication was not higher than what has been reported in lymphomas arising at other anatomic sites. Although one of our lymphomas arose at a site of previous oral hairy leukoplakia, there was no other evidence that Epstein-Barr virus replication predisposed to development or persistence of oral lymphomas. CONCLUSIONS: These data suggest that even though Epstein-Barr virus is frequently found in oral secretions, neither latent nor replicative Epstein-Barr virus is present more commonly in oral lymphomas than in lymphomas arising in other anatomic sites, when controlling for immunodeficiency status.

Adolescent↗

Sjögren syndrome associated with hepatitis C virus: a multicenter analysis of 137 cases.

To define the clinical and immunologic pattern of expression of Sjögren syndrome (SS) associated with chronic hepatitis C virus (HCV) infection, we conducted a multicenter study aiming to collect a large number of patients with SS and HCV infection. Inclusion criteria were the fulfillment of at least 4 of the classification criteria for SS proposed by the European Community Study Group and repeated positive HCV serology, confirmed by recombinant immunoblot assay and/or detection of serum HCV-RNA by polymerase chain reaction. One hundred thirty-seven patients were included (104 female and 33 male; mean age, 65 yr). Seventy-nine (58%) patients presented a systemic process with diverse extraglandular manifestations, with articular involvement (44%), vasculitis (20%), and neuropathy (16%) being the most frequent features observed. The main immunologic features were antinuclear antibodies (65%), hypocomplementemia (51%), and cryoglobulinemia (50%). Cryoglobulins were associated with a higher frequency of cutaneous vasculitis, rheumatoid factor, and hypocomplementemia. Thirty-two (23%) patients had positive anti-Ro/SS-A and/or anti-La/SS-B antibodies; these patients were predominantly women and had a higher prevalence of some extraglandular features and a lower frequency of liver involvement. Nineteen (14%) patients developed neoplasia, with hematologic neoplasia (8 cases) and hepatocellular carcinoma (6 cases) being the most frequent types. Eighty-five percent of SS-HCV patients also fulfilled the recently proposed 2002 classification criteria for SS. In conclusion, HCV-associated SS is indistinguishable in most cases from the primary form using the most recent set of classification criteria. Chronic HCV infection should be considered an exclusion criterion for the classification of primary SS, not because it mimics primary SS, but because the virus may be implicated in the development of SS in a specific subset of patients. We propose the term "SS secondary to HCV" when these patients fulfill the 2002 classification criteria for SS.

Adult↗

Bile immunoglobulin of the duck (Anas platyrhynchos). II. Antibody response in influenza A virus infections.

The capacity of the IgM-like bile immunoglobulin (IgX) of the duck (Anas platyrhynchos) to express antibody activity to H3N2 influenza A viruses, and the dependence of this activity on the co-existence of serum IgM antibodies were investigated. Ducklings infected orally and intranasally at 15-29 days of age with viruses isolated from different host species were examined for haemagglutination-inhibiting (HI) antibodies in biles and sera 16-29 days after infection (p.i.). All biles had antibodies associated with IgX; all sera had antibodies associated only with the 7.8S IgG. Following oral infection of birds 42-days-old with influenza A/duck/HK/7/75 virus, serum HI antibodies were an initial IgM response occurring from 5-12 days p.i., followed by the appearance of 7.8S IgG antibodies. Virus-neutralizing (VN) antibodies in serum were also biphasic; isotype classification was not attempted. Bile IgX developed HI and VN activity. HI antibodies reached peak titres 12 days p.i. and fell to low levels by 24 days p.i. VN antibodies also reached peak titres 12 days p.i., but thereafter persisted at quite high levels throughout the experiment. Development of high titres of antibody in bile coincided with the termination of virus excretion in faeces. These experiments confirm that bile IgX of the duck can function as antibody in response to influenza A viruses, and that its activity appears to be independent of serum IgM. Its possible relevance in determining survival of virus in the intestine is discussed.

Animals↗

euHCVdb: the European hepatitis C virus database.

The hepatitis C virus (HCV) genome shows remarkable sequence variability, leading to the classification of at least six major genotypes, numerous subtypes and a myriad of quasispecies within a given host. A database allowing researchers to investigate the genetic and structural variability of all available HCV sequences is an essential tool for studies on the molecular virology and pathogenesis of hepatitis C as well as drug design and vaccine development. We describe here the European Hepatitis C Virus Database (euHCVdb, http://euhcvdb.ibcp.fr), a collection of computer-annotated sequences based on reference genomes. The annotations include genome mapping of sequences, use of recommended nomenclature, subtyping as well as three-dimensional (3D) molecular models of proteins. A WWW interface has been developed to facilitate database searches and the export of data for sequence and structure analyses. As part of an international collaborative effort with the US and Japanese databases, the European HCV Database (euHCVdb) is mainly dedicated to HCV protein sequences, 3D structures and functional analyses.

Databases, Protein↗

The genotype of Aujeszky's disease viruses isolated in Argentina.

Genomes of four Argentine isolates of Aujeszky's disease virus (ADV) (Rio Cuarto/79, Mercedes, Chanar Ladeado-7 and Chanar Ladeado-15) from pigs were characterized and compared with four ADV strains obtained from U.S.A. (Indiana-S), Sweden (Sweden 66), France (Alfort) and Japan (Yamagata-S81) by restriction endonuclease (RE) analysis. Although three Argentine isolates were classified into type I of BamHI cleavage pattern, one isolate, Mercedes, belonged to type II, according to the classification by Herrmann et al. [6]. Since this type II virus was first isolated in 1981, no outbreak of ADV infection by this type has so far been reported in Argentina. This may imply that the immediate measures by total slaughter of pigs in the farm led successful eradication of the type II ADV infection in Argentina. This report is the first epidemiological study using RE analysis on ADV strains in this country.

Animals↗

Characterization of an alternate form of Newcastle disease virus fusion protein.

The sequence and structure of the Newcastle disease virus (NDV) fusion (F) protein are consistent with its classification as a type 1 glycoprotein. We have previously reported, however, that F protein can be detected in at least two topological forms with respect to membranes in both a cell-free protein synthesizing system containing membranes and infected COS-7 cells (J. Virol. 77:1951-1963, 2003). One form is the classical type 1 glycoprotein, while the other is a polytopic form in which approximately 200 amino acids of the amino-terminal end as well as the cytoplasmic domain (CT) are translocated across membranes. Furthermore, we detected CT sequences on surfaces of F protein-expressing cells, and antibodies specific for these sequences inhibited red blood cell fusion to hemagglutinin-neuraminidase and F protein-expressing cells, suggesting a role for surface-expressed CT sequences in cell-cell fusion. Extending these findings, we have found that the alternate form of the F protein can also be detected in infected and transfected avian cells, the natural host cells of NDV. Furthermore, the alternate form of the F protein was also found in virions released from both infected COS-7 cells and avian cells by Western analysis. Mass spectrometry confirmed its presence in virions released from avian cells. Two different polyclonal antibodies raised against sequences of the CT domain of the F protein slowed plaque formation in both avian and COS-7 cells. Antibody specific for the CT domain also inhibited single-cycle infections, as detected by immunofluorescence of viral proteins in infected cells. The potential roles of this alternate form of the NDV F protein in infection are discussed.

Amino Acid Sequence↗