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PubMed1993

Variable morphology of human immunodeficiency virus-associated lymphomas with c-myc rearrangements. The French Study Group of Pathology for Human Immunodeficiency Virus-Associated Tumors, I.

Burkitt lymphoma (BL) and immunoblastic lymphoma (IL) are the most frequent lymphoid tumors encountered in human immunodeficiency virus (HIV)-infected patients. Tumors with a morphology intermediate between BL and IL, and the existence of Burkitt's type translocations in some IL cases makes the classification of these tumors sometimes unclear. We have studied 14 cases of BL and IL in HIV-seropositive individuals with regard to clonality, Epstein-Barr virus (EBV) association, and the presence of c-myc rearrangement. Of seven tumors with morphology of BL, all were monoclonal, six showed a c-myc rearrangement and four were associated with EBV. Five tumors with morphology of IL were associated with EBV and devoid of c-myc rearrangement. Three were polyclonal representing EBV-driven lymphoproliferations similar to those observed in transplant recipients. Two tumors, one with a morphology of IL and the other intermediate between IL and BL were monoclonal, associated with EBV, and harbored a c-myc rearrangement. We propose that these last two tumors represent cases of BL that have adopted an immunoblastic morphotype in the context of acquired immunodeficiency syndrome (AIDS), reflecting the morphologic evolution of Burkitt lymphoma cells observed in culture.

Adult↗
PubMed1990

A dominant Th epitope in influenza nucleoprotein. Analysis of the fine specificity and functional repertoire of T cells recognizing a single determinant.

The sequence 260-283 of the nucleoprotein (NP) of influenza A virus is an epitope recognized by virus-immune lymph node cells from CBA (H-2k), B6 (H-2b), and B10.S (H-2s) mice. Further analysis shows that there are at least two Th epitopes within this sequence: the one close to the N-terminal (p260-273) is recognized by T cells from CBA and B6 mice while that close to the carboxyl-terminal (p270-283) is a dominant Th determinant in B10.S mice. The fine specificity of the recognition of this epitope by NP-specific T cell clones is also studied. When B10.S mice were infected intranasally or i.v. with live influenza virus, or immunized by different ways with various Ag preparations, P270-283 persistently emerged as a dominant T cell epitope. Immunization of B10.S mice with peptide p270-283 induces T cells with different in vivo functions including class II-restricted cytotoxicity, cognate help for Ag-specific antibody synthesis and delayed type hypersensitivity. This may have important implications for the understanding of the differentiation and classification of subsets of CD4+ T cells. The corresponding sequence of the NP of an equine influenza virus, A/Eq/Prague/56, which has a substitution (leucine to proline) at position 283, was not recognized by the lymph node cells from mice primed with either A/Okuda or A/Eq/Prague. However, the peptide, p270-283(E), representing this sequence induced T cell responses to both human and equine viruses. The data are discussed with respect to the development of viral vaccines.

Amino Acid Sequence↗
PubMed1994

Chronic viral hepatitis B and C: an argument against the conventional classification of chronic hepatitis.

The classification of chronic hepatitis distinguishing benign chronic persistent hepatitis from severe chronic active hepatitis was constructed without knowledge of well-defined aetiological factors. Better understanding of the different hepatitis-viruses has shed new light on this subject. Chronic viral hepatitis B and C each show typical histological patterns. The validity of the conventional classification has been evaluated by a comparative study of chronic viral hepatitis B and C. 130 biopsies from 110 patients with chronic hepatitis C (CH-C) proven serologically by antibodies (second generation testing) were compared with 105 biopsies from 73 patients with chronic hepatitis B (CH-B). These were scored semi-quantatively. In CH-C, lymphoid follicles and/or aggregates were found in 88.5%, fatty degeneration in 51%, bile duct lesions in 46.2%, and Mallory body-like material in the hepatocytes in 9.2%. The portal lymphocytic infiltration generally predominated over the necro-inflammatory lesions of the parenchyma. Chronic persistent hepatitis (defined by the presence of portal hepatitis) was present exclusively in CH-C. Chronic lobular hepatitis was found exclusively in CH-B. We conclude that the histological criteria described for CH-C are highly suggestive of the diagnosis, that the artificial subdivision of chronic hepatitis into CPH and CAH is obsolete and that the histological assessment of chronic hepatitis should consist of a grading of inflammatory activity (minimal, mild, moderate, severe) and staging of fibrosis (extent of distortion of architecture). The final diagnosis should be based on the demonstration of the aetiological agent.

Chronic Disease↗
PubMed2002

Molecular diagnosis of human enteroviruses by phylogeny-based classification by use of the VP4 sequence.

Human enteroviruses (EVs) are the major cause of a variety of acute and chronic illnesses. Virus isolation and neutralization tests are usually done to identify the causative virus, but these tests are labor intensive, time consuming, and sometimes require suckling mice from which certain viruses have been isolated. This study investigated a rapid and reliable method based on reverse-transcription polymerase chain reaction and phylogenetic analysis. The phylogenetic tree constructed by neighbor-joining on the basis of the VP4 sequence from 66 prototypes grouped all human EVs into 5 distinct clusters. These clusters correspond closely to the 5 newly designated species-human EV A-D and poliovirus. The VP4 sequences of 89 isolates from 26 serotypes obtained over >30 years plus those of 66 prototype strains were analyzed. Each isolate formed a monophyletic cluster along with its respective prototype strain, allowing for serotype identification (with the exception of E-8). VP4-based classification appears to be an effective tool for the molecular epidemiology study of EVs.

Capsid↗
PubMed1996

[Autoimmune hepatitis and hepatitis C].

From autoimmune hepatitis (AIH) classification which recognizes three types of AIH, we discuss the main relations between hepatitis C virus (HCV) infection and AIH. Type I AIH is associated with antinuclear and antismooth muscle antibodies, and with other autoimmune diseases. There is no relation between type I AIH and HCV. Type I anti-liver kidney microsome and anti-liver cytosol I antibodies represent the hallmark of type II AIH. Among type II AIH, two subgroups emerged: type IIa AIH (10-40%) are true AIH (sensitive to steroids but worsens with interferon alpha), whereas type IIb AIH (60-90%) appear as a particular form of HCV hepatitis. Type IIb AIH have a moderate activity, a low titer of autoantibodies, anti-GOR antibodies but never anti-liver cytosol I, no sensitivity to steroids but are sensitive to interferon alpha. The hallmark of type III AIH are anti-cytosol antibodies, but these AIH have the same characteristics as type I AIH. The classification between true AIH (I, IIa, III) or "pseudo-AIH" due to HCV infection has major therapeutic implications. Steroids or immunosuppressive treatments are effective in type I, IIa and III AIH but have no efficacy in type IIb AIH. Alpha interferon has an efficacy in type IIb AIH, but it has no efficacy and may even worsen hepatitis in type I, IIa and III AIH.

Autoantibodies↗
PubMed1996

Pathomorphological Characteristics and Pathogenesis of Viral Hepatitis.

Viral hepatitis (VH) is an inflammatory reaction of the liver to hepatotropic viruses. Acute VH can be classified according to the virus and type of necrosis. Chronic hepatitis (CH) might be active, persistent or lobular based on previous classification. More recently the grade (necroinflammatory activity) and stage (fibrosis and architectural distorsion) of CH have been distinguished and scored. Apoptosis and necrosis probably coexist in VH and contribute to hepatocyte death. Several "death factors", such as transforming growth factor b, Apo1/Fas and tumor necrosis factor play a role in the execution of cell death. Injury of hepatocytes during viral infection can occur as a direct effect of the virus or as a result of the host immune response. Expression of different viral antigens can be detected during VH and might be visualized. Phenotyping of the portal inflammatory cell infiltrate in CH has shown a T-cell zone comprised of CD4+ helper T cells and CD8+ supressor/cytotoxic T cells at the periphery of the lobules. The pathogenetic mechanisms responsible for the final outcome of viral infection depend on viral factors (such as genotype, mutation etc.), virus-host interaction, expression of viral protein, several cytokines etc. which finally lead to the well known histological alterations of viral hepatitis.

Journal Article↗
PubMed1986

Genomic analysis of the human B-lymphotropic virus (HBLV).

The human B-lymphotropic virus (HBLV) has a double-stranded DNA genome of greater than 110 kilobase pairs, which is consistent with its morphological classification as a herpesvirus. A 9000-base pair cloned probe of HBLV detected specific sequences in DNA and RNA of infected cells but did not hybridize to the genomic DNA of other human herpesviruses including the Epstein-Barr virus, human cytomegalovirus, herpes simplex type I, and varicella-zoster virus. Conversely, while probes obtained from each of the known human herpesvirus readily detected the homologous viral DNA, they did not hybridize to genomic HBLV DNA. This evidence, in addition to serological and morphological distinctions and the biological effects of this virus demonstrate that HBLV is a novel human herpesvirus.

Cytomegalovirus↗
PubMed1997

Cladistic analysis of Tospovirus using molecular characters.

The genus Tospovirus was thought to be composed only of the tomato spotted wilt virus (TSWV), but now at least four Tospovirus species have been proposed based on serological and molecular data. A classification of tospoviruses has been proposed taking into account global similarities of the N gene and N protein sequences of 7 isolates of Tospovirus. Because phylogenetic analyses based on global similarities can lead to classifications which do not mirror the genealogy of the group, we have employed a cladistic analysis using parsimony of this genus with RNA sequences of 450 nucleotides of the N gene from 14 new Argentinean isolates and 4 previously described isolates. Representatives of the Bunyaviridae family, Rift Valley Fever Virus (Phlebovirus) and Bunyamwera (Bunyavirus), were used as the outgroup in separate analyses.

Argentina↗
PubMed2005

Evolutionary relationships among members of the Bromoviridae deduced from whole proteome analysis.

Many molecular phylogenies of viruses build upon the analysis of single genes. The study of whole-genomes, however, might yield more reliable information to infer tree topologies and a better approach for drawing the evolutionary history of virus families. In this study, we apply a novel comparative proteomic approach to seek whether incorporating information from the entire proteome would support the actual taxonomy of the family Bromoviridae. Our results suggest that the current taxonomic classification should be modified in several aspects to account for the genomic properties of the Bromoviridae. These differences are: i) Alfalfa mosaic virus (AMV) is a true Ilarvirus instead of constituting an independent genus; ii) Pelargonium zonate spot virus (PZSV) should be considered as a member of the Bromoviridae; and iii) the genus Ilarvirus should be divided into fewer phylogenetic subgroups than suggested by antigenic differences.

Bromoviridae↗
PubMed2003

Epstein-Barr virus-associated intravascular large T-cell lymphoma presenting as acute renal failure in a patient with acquired immune deficiency syndrome.

Intravascular lymphoma (IVL) is a rare neoplasm, recently included as a specific entity in the World Health Organization classification of lymphoid tumors. Most cases are of B-cell lineage; however, rare cases of T-cell phenotype have been reported. We report a human immunodeficiency virus (HIV)-positive patient who died of acute renal failure in whom IVL was identified at autopsy, predominantly involving the renal interstitial vessels. Immunohistochemical stains revealed a T-cell phenotype, which was confirmed by T-cell receptor gamma gene rearrangement studies. The lymphoma cells showed nuclear Epstein-Barr virus (EBV)-encoded RNA transcripts by in situ hybridization, suggesting that EBV might be of etiologic importance in this tumor. The predominant involvement of kidney is unusual. With effective therapy, morbidity and mortality of HIV-1 infection has been substantially reduced, and survival times have been prolonged. However, the relative risk of secondary neoplasms, especially non-Hodgkin's lymphoma (NHL), has increased. Consequently, we conclude that unique types of NHL, such as this case of IVL, may be encountered more frequently in this patient population, and that NHL should be added to the list of differential diagnostic considerations in HIV-1-positive patients who develop acute renal failure.

Acute Kidney Injury↗
PubMed1996

Fast analysis of genomic homologies: primate immunodeficiency virus.

We have recently published a new probabilistic algorithm which performs genomic comparisons on a huge scale. In the present paper it was applied to immunodeficiency viral sequences extracted from international gene databanks. During global sequence analysis of human (HIV1 and HIV2) and simian viruses by means of dot-matrix representation, series of homology were obtained which permitted the definition of families of viruses overlapping the species divisions. Sequences of interest were characterized to the lexical base sentence through successive zoomings. Strain-to-strain comparison confirmed subfamily classifications and led, for example, to the identification of divergent LTR sequences. By way of example, we described the application of the algorithm to the ANT70C and MVP5180 HIV1-O viruses, for which the observed differences were shown to correspond to a deletion in the U3 region, situated between the LEF and NF-kappaB sites. It was of interest to consider these data in a tentative phylogenetic interpretation.

Algorithms↗
PubMed2004

Three-dimensional window analysis for detecting positive selection at structural regions of proteins.

Detection of natural selection operating at the amino acid sequence level is important in the study of molecular evolution. Single-site analysis and one-dimensional window analysis can be used to detect selection when the biological functions of amino acid sites are unknown. Single-site analysis is useful when selection operates more or less constantly over evolutionary time, but less so when selection operates temporarily. One-dimensional window analysis is more sensitive than single-site analysis when the functions of amino acid sites in close proximity in the linear sequence are similar, although this is not always the case. Here I present a three-dimensional window analysis method for detecting selection given the three-dimensional structure of the protein of interest. In the three-dimensional structure, the window is defined as the sphere centered on the alpha-carbon of an amino acid site. The window size is the radius of the sphere. The sites whose alpha-carbons are included in the window are grouped for the neutrality test. The window is moved within the three-dimensional structure by sequentially moving the central site along the primary amino acid sequence. To detect positive selection, it may also be useful to group the surface-exposed sites in the window separately. Three-dimensional window analysis appears not only to be more sensitive than single-site analysis and one-dimensional window analysis but also to provide similar specificity for inferring positive selection in the analyses of the hemagglutinin and neuraminidase genes of human influenza A viruses. This method, however, may fail to detect selection when it operates only on a particular site, in which case single-site analysis may be preferred, although a large number of sequences is required.

Amino Acid Substitution↗
PubMed2000

Genetic typing of classical swine fever virus.

Three regions of the classical swine fever virus (CSFV) genome that have been widely sequenced were compared with respect to their ability to discriminate between isolates and to segregate viruses into genetic groups. Sequence data-sets were assembled for 55 CSFVs comprising 150 nucleotides of the 5' non-translated region, 190 nucleotides of the E2 envelope glycoprotein gene and 409 nucleotides of the NS5B polymerase gene. Phylogenetic analysis of each data-set revealed similar groups and subgroups. For closely related viruses, the more variable or larger data-sets gave better discrimination, and the most reliable classification was obtained with sequence data from the NS5B region. No evidence was found for intertypic recombination between CSFVs. A larger data-set was also analysed comprising 190 nucleotides of E2 sequence from 100 CSFVs from different parts of the world, in order to assess the extent and global distribution of CSFV diversity. Additional groups of CSFV are evident from Asia and the nomenclature of Lowings et al. (1996) [Lowings, P., Ibata, G., Needham, J., Paton, D., 1996. J. Gen. Virol. 77, 1311-1321] needs to be updated to accommodate these. A tentative assignment, adapting rather than overturning the previous nomenclature divides CSF viruses into three groups with three or four subgroups: 1.1, 1.2, 1.3; 2.1, 2.2, 2.3; 3.1, 3.2, 3.3, 3.4. The expanding data-base of CSFV sequences should improve the prospects of disease tracing in the future, and provide a basis for a standardised approach to ensure that results from different laboratories are comparable.

Animals↗
PubMed2025

Distinct Evolutionary Signatures of Human Parainfluenza Viruses 2 and 4 Reveal Host Antagonism Divergence and Phylogenetic Discordance.

Human parainfluenza virus 2 (HPIV-2) and human parainfluenza virus 4 (HPIV-4) are significant but underappreciated respiratory pathogens, particularly among high-risk populations including children, the elderly, and immunocompromised individuals. In this study, we sequenced 101 HPIV-2 and HPIV-4 genomes from respiratory samples collected in western Washington State and performed comprehensive evolutionary analyses using both new and publicly available sequences. Phylogenetic and phylodynamic analyses revealed that both HPIV-2 and HPIV-4 evolve at significantly faster rates compared to the mumps virus, a reference human orthorubulavirus. Notably, while HPIV-2 demonstrated the highest evolutionary rates in the surface glycoprotein HN, consistent with humoral immune-driven selection, the innate immune antagonist V/P gene evolved fastest in HPIV-4. We identified a hypervariable region within the HPIV-4V/P protein (residues 35 to 75), which structural modeling placed in a loop overlapping a known interferon antagonism domain in other paramyxovirus V proteins, though HPIV-4 is functionally incompetent in this activity. Expanded phylogenetic analysis across the Paramyxoviridae family uncovered a striking evolutionary discordance: while the HN glycoprotein and L polymerase of HPIV-4 and its 2 closest bat-derived viruses clustered within the Orthorubulavirus genus, their nucleoprotein (N), phosphoprotein (P), matrix (M), and fusion (F) proteins formed a distinct lineage outside the Rubulavirinae subfamily. Together, these findings highlight the distinct evolutionary trajectories of HPIV-2 and HPIV-4, raise hypotheses around complex Paramyxoviridae zoonotic events including recombination-like patterns, and demonstrate limitations of current L protein-based taxonomic classification schemes.

Humans↗
PubMed2006

[Prevalence of lymphoma subtypes in Shanxi according to latest WHO classification].

OBJECTIVE: To analyze the prevalence of lymphoma subtypes in Shanxi according to the latest World Health Organization (WHO) classification, and to compare the figures with those in other parts of the world. METHODS: The hematoxylin and eosin-stained sections of 447 lymphoma cases from the archive files of Shanxi Tumor Hospital were reviewed. Immunohistochemical study was performed using a panel of antibodies, including ALK1, bcl-6, CD (1a, 3, 4, 5, 7, 8, 10, 15, 20, 23, 30, 43, 56, 68, 79a and 99), cyclin D1, EMA, IgD, kappa, lambda, LMP1, PAX5, TdT and Vs38C. In addition, in-situ hybridization for Epstein-Barr virus-encoded RNA (EBER) was carried out. All cases were then reclassified according to the latest WHO classification of lymphoma. RESULTS: Of the 447 cases studied, 385 cases (86.1%) were confirmed to be non-Hodgkin lymphoma (NHL), while 62 cases (13.9%) belonged to classic Hodgkin lymphoma (HL). Of the NHL cases, 68.3% were of B-cell lineage and 30.6% were of T and/or NK-cell lineage. Histiocytic neoplasm accounted for only 0.8% (3 cases). As for the subtyping of NHL, diffuse large B-cell lymphoma was commonest (35.1%), followed by peripheral T-cell lymphoma, NOS (12.0%), extranodal marginal zone B-cell lymphoma (MALT lymphoma) (11.7%), follicular lymphoma (8.6%), T-lymphoblastic lymphoma (7.0%), anaplastic large cell lymphoma (4.2%), B-small lymphocytic lymphoma (3.6%) and mantle cell lymphoma (2.6%). Amongst the 263 cases of B-cell lymphoma, 105 cases (39.9%) expressed immunoglobulin light chain (kappa in 52 cases and lambda in 53 cases) in paraffin sections. Regarding markers for EB virus infection, 14 cases of the B-cell lymphoma gave positive findings with both EBER in-situ hybridization and LMP-1 immunohistochemistry, while 6 of the T/NK-cell lymphoma expressed LMP-1 and 19 showed positive signals for EBER. In NHL, there was discordance in EBER in-situ hybridization and LMP-1 immunohistochemical results. As for HL, EB virus positivity was noted in 37 of the 62 cases (59.7%), including 7 cases of lymphocyte-rich HL, 11 cases of mixed cellularity HL and 19 cases of nodular sclerosis HL. In classic HL, there was complete concordance of results by both EBER in-situ hybridization and LMP-1 immunohistochemistry. CONCLUSIONS: The prevalence of diffuse large B-cell lymphoma in Shanxi is similar to that in America, Australia, Japan and Korea. The incidence of follicular lymphoma however is much lower than America and Australia.

Adolescent↗
PubMed1975

Failure of rubella virus to replicate in mosquitos.

Rubella virus failed to replicate in mosquitoes (Aedes albopictus and Culex fatigans) following parenteral inoculation. The virus demonstrated in mosquitoes tested immediately after inoculation but was not detected in insects sampled 7, 14 and 21 days postinoculation. This experiment provides further evidence that rubella is not an arbovirus, but does not invalidate its classification as a togavirus.

Aedes↗
PubMed1994

Viral respiratory diseases in children: classification, etiology, epidemiology, and risk factors.

The epidemiology, molecular structure, cell tropism, and pathophysiology of many human disease-causing viruses have been painstakingly and elegantly characterized during the past 50 years. Vaccines and antiviral drugs of varying efficacy were developed and tested. Despite the relegation of smallpox to a freezer chest and the progress in the control of measles and hepatitis B, the viruses that cause respiratory tract infections remain significant causes of illness and death in pediatric populations worldwide. This discussion surveys the virus groups that contain nearly 200 distinct viruses that cause sporadic and epidemic respiratory infections in children. The epidemiology of infection with the influenza A and B, parainfluenza, and respiratory syncytial viruses and adenoviruses and their impact on infants and children and the groups at highest risk for morbid outcomes are discussed.

Acute Disease↗