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PubMed2002

Molecular phylogeny and proposed classification of the simian picornaviruses.

The simian picornaviruses were isolated from various primate tissues during the development of general tissue culture methods in the 1950s to 1970s or from specimens derived from primates used in biomedical research. Twenty simian picornavirus serotypes are recognized, and all are presently classified within the Enterovirus genus. To determine the phylogenetic relationships among all of the simian picornaviruses and to evaluate their classification, we have determined complete VP1 sequences for 19 of the 20 serotypes. Phylogenetic analysis showed that A13, SV19, SV26, SV35, SV43, and SV46 are members of human enterovirus species A, a group that contains enterovirus 71 and 11 of the coxsackie A viruses. SA5 is a member of human enterovirus species B, which contains the echoviruses, coxsackie B viruses, coxsackievirus A9, and enterovirus 69. SV6, N125, and N203 are related to one another and, more distantly, to species A human enteroviruses, but could not be definitely assigned to a species. SV4 and SV28 are closely related to one another and to A-2 plaque virus, but distinct from other enteroviruses, suggesting that these simian viruses are members of a new enterovirus species. SV2, SV16, SV18, SV42, SV44, SV45, and SV49 are related to one another but distinct from viruses in all other picornavirus genera, suggesting that they may comprise a previously unknown genus in Picornaviridae. Several simian virus VP1 sequences (N125 and N203; SV4 and SV28; SV19, SV26, and SV35; SV18 and SV44; SV16, SV42, and SV45) are greater than 75% identical to one another (and/or greater than 85% amino acid identity), suggesting that the true number of distinct serotypes among the viruses surveyed is less than 20.

Animals↗
PubMed2002

Genus Coltivirus (family Reoviridae): genomic and morphologic characterization of Old World and New World viruses.

We report a genomic and morphologic study of the European Eyach (EYA) virus (genus Coltivirus, family Reoviridae) and a comparative analysis with the American Colorado tick fever (CTF) virus (the type species of the genus). The previously established, but distant, antigenic relationship between these viruses was strengthened by genetic findings (presence of cognate genes, amino acid identity between 55 and 88%, similar conserved terminal motifs, suspected read-through phenomenon in segment 9 of both viruses) and by indistinguishable ultramicroscopic morphologies. Moreover, putative constitutive modifying enzyme activities were suspected to be carried out by homologous viral proteins (RNA-dependent RNA polymerase, methyl/guanylyl transferase, NTPase). These findings, together with the comparative analysis to genomes of southeast Asian isolates, support the recent classification of arboviruses with 12 segments of dsRNA within two distinct genera (genus Coltivirus and genus Seadornavirus) and raise interesting questions about the evolutionary origins of coltiviruses. The previously proposed hypothesis that EYA virus was derived from an ancestral virus introduced in Europe with the migration of lagomorphs from North-America, would imply a divergence date between American and European isolates of over 50 million years ago (MYA). This analysis allows for the first time to propose an evolutionary rate for virus dsRNA genomes which was found to be in the order of 10(-8) to 10(-9) mutations/nt/year, a rate similar to that of dsDNA genomes.

Americas↗
PubMed1969

Temperature of compensation: significance for virus in- activation.

The purpose of this report is to call attention to the probable biological utility of a physical constant, the temperature of compensation (T(c)) or isokinetic temperature. T(c) has hitherto not been used in biological research. It is defined as the temperature at which a series of Arrhenius plots, related by variation of a single parameter, pass through a common point. Such systems demonstrate the so-called compensation effect and show linear variation of change in enthalpy with change in entropy; the slope [unk] H/[unk]S is T(c). Related reactions in which, for example, solvent change or structural change of the reactants does not change the mechanism of the reaction or the nature of the transition state exhibit an identical T(c). The system used in this study was a complex one, i.e., protection against thermal inactivation of Sindbis virus by HPO(4) (=) and SO(4) (=). The time-rate constant of loss of infectivity was determined at different temperatures for virus suspended in different salt concentrations at constant pH. The compensation effect was demonstrated and T(c) was found to be approximately 57 degrees C for virus inactivation in both Na(2)HPO(4) and MgSO(4) solutions. The intercept of a DeltaSdouble dagger/DeltaHdouble dagger plot, defined as the constant B, also was the same for the two salts. We suggest that determination of T(c) in biological systems might be of value in (1) establishment of whether an observed phenomenon results from the same process or mechanism as another observed phenomenon; (2) prediction of rates or other behavior under relevant conditions; and (3) classification.

Arboviruses↗
PubMed2002

Detection of Epstein-Barr virus and human T-cell lymphotropic virus type 1 in malignant nodal lymphoma, studied in Okinawa, a subtropical area in Japan.

Formalin-fixed paraffin-embedded lymph node samples were collected from 100 cases of malignant nodal lymphoma documented in Okinawa in the period from 1973 through 1998. According to the new World Health Organization classification, 12 cases were Hodgkin's lymphoma (HL). Eighty-eight cases of non-Hodgkin's lymphoma (NHL) included 54 cases of T-cell type and 34 cases of B-cell type. Using polymerase chain reaction (PCR), Epstein-Barr virus (EBV) was detected in 11 cases (91.7%) of HL and in 57 cases (64.8%) of NHL, and human T-cell lymphotropic virus type 1 (HTLV-1) was detected in 23 cases (26.1%) of NHL. Clonal integration of HTLV-1 was detected in 10 (43.5%) of 23 HTLV-1 PCR-positive cases by the inverse PCR technique. The EBV-infected cells were detected by EBER-1 in situ hybridization in 11 (91.7%) of 12 HL cases and in 64 (72.7%) of 88 NHL cases. Irrespective of phenotype and tissue type of the malignant lymphoma, the rate of EBV-positive infection in Okinawa was higher than that in any other districts reported in Japan. This characteristic high rate of EBV-positive infection in Okinawa can be ascribed to various factors, such as racial and geographical differences.

Clone Cells↗
PubMed1986

Nucleotide sequence analysis of the long terminal repeat of integrated caprine arthritis encephalitis virus.

The nucleotide sequence of the long terminal repeat (LTR) of caprine arthritis encephalitis virus (CAEV), a prototype lentivirus was determined. 6-bp directly repeated host cell sequences flank the 376-bp proviral LTRs. By comparison with other retroviral sequences, the CAEV LTR likely contains U3, R and U5 regions 207, 86 and 83 base-pairs in length, respectively. Sequences conforming to consensus transcriptional promoter sites were identified in the U3 region upstream of a potential transcription initiation site. A consensus polyadenylation signal is present 20 bases upstream of the putative R-U5 border and a potential poly(A) addition site. Sequence comparisons of the CAEV LTR with those of other retroviruses uncovered significant similarities with that of visna virus. No other global homologies with other retrovirus LTRs could be detected. CAEV utilizes a primer binding site complementary to lysine tRNA as does visna, AIDS associated retroviruses, and mouse mammary tumor virus. The putative primer for positive-strand DNA synthesis identified in the CAEV sequence is identical to that of visna virus and very similar to those of AIDS retroviruses and MMTV. In addition, a stretch that includes the TATA box of the CAEV LTR resembles closely the corresponding region in the AIDS retrovirus. These and other findings further strengthen the classification of AIDS retrovirus as a lentivirus.

Animals↗
PubMed1998

Comparative analysis of Epstein-Barr virus (EBV) detection by nested-PCR and non-isotopic in situ hybridization in nasopharyngeal carcinoma (NPC).

The aims of this study were two-fold: first, to assess the relative diagnostic performance of non-isotopic in situ hybridization (ISH) and the nested polymerase chain reaction (nested-PCR) applied to Epstein-Barr virus (EBV) detection in a series of 55 unselected nasopharyngeal carcinoma (NPC) cases and, secondly, to correlate these data with histopathological classification. Our study shows that in 76.36% of NPC cases positive nuclear signals were observed using EBV-ISH. Overall, EBV-ISH positivity varied according to histological type, in that undifferentiated carcinomas showed a higher proportion of positive cases than differentiated cell carcinomas, although ISH results do not show significant differences in relation to histological types when employing two different schemes (WHO and Micheau). However, in adequate quality DNA samples (54 NPC cases), EBV-DNA was detected in 100% of cases using a nested-PCR, supporting the previous view that all histological types of NPC are in reality variants of EBV-infected neoplasia. ISH-negative cases probably reflect a lower sensitivity than PCR, particularly when a small number of viral copies are present, as well as a variable technical effectiveness for detected EBV, independent of the NPC histological type.

Adolescent↗
PubMed1995

Classification of HIV infection and disease in women from Rwanda. Evaluation of the World Health Organization HIV staging system and recommended modifications.

OBJECTIVE: To develop a human immunodeficiency virus (HIV) staging system for sub-Saharan Africa on the basis of an evaluation of the World Health Organization (WHO) system and predictors of mortality. DESIGN: Prospective cohort study with 4 years of follow-up. SETTING: Kigali, Rwanda. PATIENTS: 412 HIV-infected women recruited from prenatal and pediatric clinics. MEASUREMENTS: Clinical signs and symptoms of HIV disease, laboratory assays (including complete blood count and erythrocyte sedimentation rate), and cumulative mortality. RESULTS: The WHO staging system includes a clinical and a laboratory axis. The clinical axis was revised by inclusion of oral candidiasis, chronic oral or genital ulcers, and pulmonary tuberculosis as "severe" disease (clinical stage IV); in addition, body mass index was substituted for weight loss in the definition for the wasting syndrome. The 36-month cumulative mortality was 7% for women in modified clinical stage I ("asymptomatic"), 15% for those in stage II, 19% for those in stage III, and 36% for those in stage IV (P < 0.001). The laboratory axis was revised by replacing lymphocyte count with hematocrit and erythrocyte sedimentation rate. The 36-month mortality was 10% for women in modified stage A ("normal" laboratory results) and 33% for those in stage B (erythrocyte sedimentation rate > 65 mm/h or hematocrit < 0.38) (P < 0.001). A single staging system combining clinical and laboratory criteria is proposed, with a 36-month mortality of 7% for women in combined stage I, 10% for those in stage II, 29% for those in stage III, and 62% for those in stage IV (P < 0.001). CONCLUSIONS: On the basis of this analysis, a staging system relevant for sub-Saharan Africa is proposed that reflects the range of HIV-related outcomes, has strong prognostic significance, includes inexpensive and available laboratory tests, and can be used by both clinicians and researchers.

AIDS-Related Opportunistic Infections↗
PubMed1989

Classification, distribution and importance of arboviruses.

This essay reviews in concise form an extensive subject. Arborviruses belong to a number of different taxonomic groups, some of which include viruses not transmitted by arthropods. A state of the art definition of arboviruses is given which does recognise the importance of vertical transmission in arthropods to the basic maintenance of some arboviruses. Most of the arboviruses which affect humans are included in the families Togaviridae, Flaviviridae, Bunyaviridae, Reoviridae and Rhabdoviridae. Many arbovirus infections are symptomless. Clinical manifestations range from mild febrile illness, which may or may not be accompanied by skin rash and by arthralgia, to severe and often fatal encephalitis or haemorrhagic fever with shock. Three arboviral diseases considered at present as the most important ones are discussed in more detail: dengue and dengue haemorrhagic fever (DHF), yellow fever and Japanese encephalitis (JE). They have caused some of the most devastating epidemics in recent years. DHF has developed into a major paediatric problem in South East Asia and the Western Pacific with over 6,000,000 hospital admissions and 20,000 deaths in the two regions over the last 20 years. Spectacular outbreaks of yellow fever, such as the one in Ethiopia in 1960-1962 with 15,000-30,000 estimated deaths, still occur in Africa in areas contiguous to rain forest regions where jungle yellow fever is enzootic. JE is characterized by significant mortality in children and old people in many countries of Asia, where the epidemiological patterns and the distribution of the disease have changed in recent years. The complex interrelated factors which are involved in arbovirus ecology are illustrated.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Two major types of JC virus defined in progressive multifocal leukoencephalopathy brain by early and late coding region DNA sequences.

A 610-bp region of the JC virus (JCV) genome sequenced from brains of 11 progressive multifocal leukoencephalopathy (PML) patients contains 20 sites of point mutations that allow reliable classification of JCV isolates into two types. These type-determining sites were located in the region extending from position 2131 in the VP1 gene, through the intergenic region, to position 2740 in the T antigen gene. At these 20 sites the presence of different nucleotides creates two distinct patterns of substitution, with six isolates having the Type 1 pattern and five having the Type 2 pattern. Only four of the 11 isolates had 'crossovers' to the opposite type consensus DNA sequence at a small number of sites, indicating a very high type specificity. Additionally, three type-determining sites occur in the non-coding region to the left of the origin of replication. Other mutations occurred at random sites, making each strain unique, although one strain, 105, is identical to the Type 1 consensus. The JCV prototype strain Mad-1 was found to be Type 1 and differs from the consensus sequence at five sites. The other previously sequenced JCV strain, GS/B, is Type 2. At three sites out of five in the T antigen C terminus there is a type-specific amino acid substitution; however, none of the type-determining mutations in the VP1 gene cause an amino acid substitution. Comparison of each type's consensus DNA sequence to that of BK virus suggests that Type 2 represents the ancestral JCV sequence from which Type 1 diverged during human evolution.

Antigens, Polyomavirus Transforming↗
PubMed1995

Primary central nervous system lymphomas--new pathological developments.

Primary central nervous system lymphomas (PCNSL) show increased incidence both in immunocompromised high-risk groups and in the general population. They are extranodal diffuse non-Hodgkin's lymphomas with a morphology similar to systemic lymphomas, but differ in their biological and molecular behaviour. The majority are large B-cell variants of high-grade malignancy; low-grade subtypes and T-cell lymphomas are rare; up to 50% remain unclassified according to the New Working Formulation and updated Kiel classification. Monoclonality of immunoglobulin receptor gene rearrangement can be diagnostically useful. The pathogenesis of PCNSL is obscure. Epstein-Barr virus (EBV) genome/proteins expression in two-thirds of HIV-related PCNSL but only in 15% of those in immunocompetent patients suggest different EBV latency stages in both types; human herpesvirus type 6 does not appear to play a pathogenic role. Comparison of expression patterns of integrin chains and adhesion molecules are very similar for PCNSL and nodal lymphomas suggesting that they are not selective mediators of lymphoma cell homing to the brain. In HIV-negative PCNSL they appear not to be influenced by EBV. Studies of protooncogenes (bcl-1 and bcl-2 genes) revealed no rearrangement in PCNSL, suggesting that they are not involved in the pathogenesis of PCNSL that probably do not differ cytogenetically from nodal B-cell lymphomas. Since most of the currently known molecular parameters are probably not the primary pathogenic events, the molecular genetics and pathogenesis of PCNSL are still to be elucidated.

Cell Adhesion Molecules↗
PubMed1992

Prognostic factors and survival in children with perinatal HIV-1 infection. The Italian Register for HIV Infections in Children.

The signs that may arise after perinatal infection with human immunodeficiency virus type 1 (HIV-1) have been classified by the Centers for Disease Control, but the clinical usefulness of the classification system and the prognostic importance of each disease pattern have not been established. We sought to address these issues by analysing data from the Italian Register for HIV infection in children. We studied 1887 children born to HIV-1-seropositive mothers. 1045 were identified at birth and the others were registered later (median age 4.8 [range 0.4-72] months). HIV-1-associated signs developed in 433 (81.8%) of 529 seropositive infected children at a median age of 5 (0.03-84) months. These signs appeared significantly earlier in the 102 children who died of HIV-1-related illness than in those who are still alive (median 3 [0.03-55] vs 6 [0.03-84] months; p less than 0.001). The cumulative proportion surviving at age 9 years was 49.5% (95% confidence interval 27-65%) and the median survival time was 96.2 months. Separate analysis of the 112 seropositive infected children followed from birth and older than 15 months gave similar results. Hepatomegaly, splenomegaly, lymphadenopathy, parotitis, skin diseases, and recurrent respiratory tract infections formed the mildest disease pattern. Lymphoid interstitial pneumonitis and thrombocytopenia were signs of intermediate disease. By contrast, in multivariate analysis specific secondary infectious diseases, severe bacterial infections, progressive neurological disease, anaemia, and fever were significant and independent negative predictors of survival. Growth failure, persistent oral candidosis, hepatitis, and cardiopathy were associated in univariate analysis with significantly shorter survival. Our findings suggest that the outlook for children with perinatal HIV-1 infection is better than previously thought and that a new clinical staging system of single disease patterns is needed.

Acquired Immunodeficiency Syndrome↗
PubMed2005

Influenza-like illness criteria were poorly related to laboratory-confirmed influenza in a sentinel surveillance study.

OBJECTIVE: To analyze the most related clinical data for influenza and the utility of influenza-like illness criteria as the clinical threshold for sampling in an influenza sentinel surveillance over a 3-year period. METHODS: Sentinel physicians collected throat specimens and data from outpatients with acute respiratory infection (< or = 72 hours duration). Laboratory-confirmed influenza infection was compared with independent symptoms and the influenza-like illness criteria, as defined by the Classification Committee of the World Organization of Family Doctors. RESULTS: From 1934 patients, 359 (18.56%) yielded positive results for influenza viruses. Only 199 (55.4%) of laboratory-confirmed cases fulfilled clinical criteria of influenza-like illness: positive and negative predictive value (PPV and NPV) of 0.36 and 0.88, respectively. Fever, cough, and rhinorrhea individually correlated with influenza infections (PPV: 0.30, 0.20, and 0.20, respectively; NPV: 0.92, 0.87, and 0.85, respectively). Multivariate analysis demonstrated that the correlation of influenza infection with the presence of fever and cough was similar to the correlation between influenza infection and influenza-like illness criteria (odds ratio 2.24 vs. 2.71, respectively). CONCLUSION: Influenza-like illness criteria are poorly related to laboratory-confirmed influenza. For early detection of influenza viruses in surveillance systems, a less restrictive clinical criterion (specifically, acute respiratory infection) perhaps should be followed.

Acute Disease↗
PubMed1997

Association of cumulative allelic losses with tumor aggressiveness in hepatocellular carcinoma.

BACKGROUND/AIMS: Loss of heterozygosity on various chromosomal arms has been reported in hepatocellular carcinoma and a multistep accumulation of genetic alteration has become accepted as the mechanism underlying progression of the disease. Although cumulative genetic alterations may imply more malignant tumors with poorer prognosis, the assumption requires further investigation. METHODS: Presence of loss of heterozygosity was analyzed by microsatellite markers at 13 loci on six chromosomal arms in 56 hepatocellular carcinomas. Association with cumulative allelic losses and prognosis of the patient following curative resection was studied. RESULTS: Frequency of allelic losses at each chromosomal arm was 31% on 1p, 20.6% on 4q, 17.5% on 8p, 17.5% on 13q, 25.5% on 16q and 17.4% on 17p. Thirty-three tumors (59%) presented loss of heterozygosity. Tumors with more allelic losses were significantly more likely to be un-infected by hepatitis C virus, and to be histologically poorly differentiated, to have higher alpha-feto protein value, to be advanced in T classification and in tumor stage. Patients with more than one loss of heterozygosity revealed poorer 3-year disease-free survival than those with one or no (p=0.0004). A multivariate Cox model analysis revealed cumulative loss of heterozygosity as an independent and influential factor for disease recurrence (relative risk, 2.66; 95% confidence interval, 1.23-5.75; p=0.013), followed by tumor stage. CONCLUSIONS: Cumulative loss of heterozygosity reflects the multistep genetic mechanism of progression of hepatocellular carcinoma. The study confirms the potential significance of genetic analysis in the management of the disease.

Adult↗