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PubMed1994

Median rhomboid glossitis. An oral manifestation in patients infected with HIV.

A follow-up study included the oral examination of 39 persons known to be infected with the human immunodeficiency virus. In addition to the other human immunodeficiency virus-associated oral lesions, lesions clinically similar to the smooth form of median rhomboid glossitis, which is now believed to be erythematous candidiasis located in the dorsum of the tongue, were found in seven patients (18%). Patients with median rhomboid glossitis were classified in different stages of the Centers for Disease Control 1986 classification system and showed an average of CD+4 cell counts 397.5/mm3. Also the presence or the absence of anti-p24 antibodies in the serum and stimulated whole saliva of the patients with median rhomboid glossitis did not correlate with the stage of the disease or with low levels of CD+4 cell counts as in other forms of oral candidiasis. Therefore our results suggest that median rhomboid glossitis should be included as a distinct form of oral candidiasis in the classification of the oral manifestations of infection with the human immunodeficiency virus.

AIDS-Related Opportunistic Infections↗

PubMed1996

Predictors of survival in human immunodeficiency virus type 1-seropositive intravenous drug users.

In an ongoing prospective study of street-recruited intravenous drug users (IDUs) in Miami, Fla., 116 human immunodeficiency virus type 1 (HIV-1)-infected IDUs were monitored for up to 7 years. This provided an opportunity to evaluate baseline immunological parameters as potential predictors of survival among HIV-1-infected IDUs. As expected, HIV-1-infected IDUs who had an advanced stage of the disease (Centers for Disease Control and Prevention classification III or IV); p24 antigenemia; human T-cell leukemia virus type 1/2 seropositivity; low CD4 counts (< or = 200); low hemoglobin (< or = 14), high serum immunoglobulin A (IgA) (> 500 mg/dl), or high serum IgG (> or = 3,500 mg/dl) levels; or low proliferative responses to pokeweed mitogen (< or = 1,500 cpm) and to phytohemagglutinin (< or = 80,000 cpm) at baseline had worse survival rates. Results from multivariate Cox's models of survival showed that the baseline serum IgG level, serum IgA level, and CD4 count independently predict survival in HIV-1-infected IDUs. Cross-validation procedures verified the above-mentioned findings. These findings support the routine consideration of serum immunoglobulin levels in addition to CD4 count, especially in early evaluation of disease stage, as these evaluations may modify application of prophylaxis and treatment for HIV-1-infected IDUs. We recommend consideration of use of serum IgG and IgA as immunological markers for long-range prediction of survival in HIV-1-infected IDUs. These determinations are less onerous and more appropriate for use in field studies and financially less favored settings.

Adult↗

PubMed2002

Comparison of methodologies for quantification of hepatitis C virus (HCV) RNA in patients coinfected with HCV and human immunodeficiency virus.

Quantification of hepatitis C virus (HCV) RNA is important in the assessment of HCV-associated liver disease in patients coinfected with HCV and human immunodeficiency virus (HIV). To investigate whether the standard integrity of competing test methodologies might be compromised by higher HCV titers in coinfected patients, 2 technologies (a polymerase chain reaction-based assay [COBAS Amplicor 2.0 assay; Roche Diagnostics] and a branched-chain DNA assay [Versant 3.0; Bayer]) were evaluated by testing paired serum samples from 68 coinfected patients and 137 HCV-monoinfected patients. Although the correlation was highly significant (r=0.81; P<.001), HCV RNA titers expressed in international units per milliliter could not be standardized; statistically significant differences were observed in all quartiles. Significant variability (P<.0007) was observed in the classification of patients as having a high versus a low virus titer (cutoff, 800,000 IU/mL), which suggests that standardization in international units has low efficacy among coinfected patients. Clinicians should note that test variability precludes direct comparability of HCV RNA titers, particularly in coinfected patients with high titers.

Adult↗

PubMed2005

Molecular identification of mumps virus genotypes from clinical samples: standardized method of analysis.

A sensitive nested reverse transcription-PCR assay, targeting a short fragment of the gene encoding the small hydrophobic protein (SH gene), was developed to allow rapid characterization of mumps virus in clinical samples. The sensitivity and specificity of the assay were established using representative genotypes A, B, C, D, E, and F. Mumps virus RNA was characterized directly from cerebrospinal fluid (CSF) samples and in extracts of mumps virus isolates from patients with various clinical syndromes. Direct sequencing of products and subsequent phylogenetic analysis enabled genetic classification. A simple web-based system of sequence analysis was established. The study also allowed characterization of mumps virus strains from Argentina as part of a new subgenotype. This PCR assay for characterization of mumps infections coupled to a web-based analytical program provides a rapid method for identification of known and novel strains.

Amino Acid Sequence↗

PubMed2001

Epstein-Barr virus detection in non-Hodgkin's lymphoma of the oral cavity: an immunocytochemical and in situ hybridization study.

OBJECTIVE: The purpose of this study was to histologically characterize a series of oral non-Hodgkin's lymphomas (NHLs) and to investigate latent and lytic Epstein-Barr virus (EBV) infection in these. STUDY DESIGN: The revised European-American Lymphoma classification system (41) was used to categorize 58 cases of oral NHL, which included 9 immunosuppression-related NHLs. EBV infection was determined by in situ hybridization for Epstein-Barr virus-encoded RNA and by immunohistochemistry for the EBV antigens latency membrane protein, Epstein-Barr nuclear antigen-2 (EBNA2) and Z EBV replication activator protein. RESULTS: Most tumors were B-cell lymphomas (78%), but the proportion of T-cell lymphomas was surprisingly high (22%). The most common histologic subtypes were diffuse large B-cell lymphomas (45%), peripheral T-cell lymphomas (19%), and follicle center lymphomas (14%). Two thirds of the known immunosuppression-related NHLs were T-cell lymphomas. All of the immunosuppression-related tumors were EBV-infected, whereas the EBV infection rate in the NHLs of the remaining patients presumed to be immunocompetent was only 9%. Most EBV-positive tumors expressed neither of the latent antigens (ie, latency membrane protein and Epstein-Barr nuclear antigen-2), and coexpression of the 2 was observed only in immunosuppressed patients. Z EBV replication activator protein expression, which is indicative of replicative infection, occurred only in immunosuppressed individuals. CONCLUSIONS: Diffuse large B-cell lymphomas were the most common histologic subtype of oral NHLs, but T-cell lymphomas were relatively common and frequently occurred in states of immunosuppression. EBV may play a limited role in the initiation of lymphoma in the immunocompetent patient, but the virus may be of importance in progression of the disease in those patients with more aggressive tumors, as immunosuppression occurs.

Adult↗

PubMed2004

Acute rejection and graft survival in renal transplanted patients with viral diseases.

Transplanted patients are susceptible to viral infections; thus, the aim of this study was to evaluate the features of acute rejections and the outcome of the renal graft in transplanted patients with herpes virus diseases. Renal biopsies from 30 renal transplanted patients undergoing early acute rejection (type IA and IB according to the Banff 97 classification) were evaluated. In total, 15 of these patients experienced cytomegalovirus (CMV) or Epstein-Barr virus disease within the first year following transplantation (group I) and 15 patients showed no evidence of viral infection (group II). No significant differences between the groups in terms of age, male/female ratio, living/cadaveric donor ratio, cold ischemia time, HLA A-B matching, pretransplant panel reactive antibody test, occurrence of post-transplant tubular necrosis, plasma levels of cyclosporin A and mean percent increase of serum creatinine at the time of the biopsy were observed. In group I biopsies, the mean number of interstitial plasma cells, as well as the mean number of CD79a-positive cells (B lymphocytes and plasma cells) was significantly higher than in group II (P<0.01 and <0.01, respectively). There was a positive correlation between the number of infections and the number of plasma cells (P<0.05). In transplanted patients, CMV can trigger the formation of anti-endothelial cell antibodies, which have been proposed to play a role in antibody-mediated rejections. We investigated whether a deposition of C4d, a marker of antibody-mediated reactions, was present in renal peritubular capillaries. In group I C4d deposition was found in five cases, while in group II it was not observed (P<0.05). In group I, 7/15 patients developed chronic allograft nephropathy vs 1/15 patients in group II (P<0.05). The estimated 1-, 5- and 8-year cumulative graft survival rates were 80, 66 and 57%, respectively, in group I, while in group II the estimated 8-year cumulative survival rate was 100% (P<0.05). In conclusion, acute rejection biopsies of patients with viral infections displayed plasma cell infiltrates and, in several cases, C4d deposition. Our study suggests a role of B lymphocytes in the pathology of these rejections and confirms the association between viral infections and poor graft survival.

Adult↗

PubMed1993

RNA sequence of astrovirus: distinctive genomic organization and a putative retrovirus-like ribosomal frameshifting signal that directs the viral replicase synthesis.

The genomic RNA of human astrovirus was sequenced and found to contain 6797 nt organized into three open reading frames (1a, 1b, and 2). A potential ribosomal frameshift site identified in the overlap region of open reading frames 1a and 1b consists of a "shifty" heptanucleotide and an RNA stem-loop structure that closely resemble those at the gag-pro junction of some retroviruses. This translation frame-shift may result in the suppression of in-frame amber termination at the end of open reading frame 1a and the synthesis of a nonstructural, fusion polyprotein that contains the putative protease and RNA-dependent RNA polymerase. Comparative sequence analysis indicated that the protease and polymerase of astrovirus are only distantly related to the respective enzymes of other positive-strand RNA viruses. The astrovirus polyprotein lacks the RNA helicase domain typical of other positive-strand RNA viruses of similar genome size. The genomic organization and expression strategy of astrovirus, with the protease and the polymerase brought together by predicted frameshift, most closely resembled those of plant leuteoviruses. Specific features of the sequence and genomic organization support the classification of astroviruses as an additional family of positive-strand RNA viruses, designated Astroviridae.

Base Sequence↗

PubMed1999

Overview of posttransplant B-cell lymphoproliferative disorders.

Epstein-Barr virus-associated B-cell lymphoproliferations are a serious complication of organ or bone marrow transplantation whose incidence is strongly influenced by a number of risk factors. The disease represents a model of Epstein-Barr virus-driven lymphoid neoplasia in the setting of immunodeficiency. The incidence and pathogenesis of posttransplant lymphoproliferations are examined in relation to the nature of the transplanted organ, the Epstein-Barr virus infection, and the use of specific immunosuppressive regimens. Pathologic classifications and molecular mechanisms for neoplasia are reviewed. Clinical manifestations, pathologic features, and diagnostic considerations are summarized, with emphasis on those aspects that differ significantly from classic non-Hodgkin's lymphoma. Existing data regarding treatment are reviewed, including reduction in immunosuppression, surgery, radiation, chemotherapy, interferon-alpha, monoclonal anti-B-cell antibodies, and T-cell therapy. A basis for the selection of therapeutic options is suggested.

Cell Transformation, Neoplastic↗

PubMed1996

Virology of hepatitis C virus.

Hepatitis C virus (HCV) has been identified as the main causative agent of posttransfusion non-A, non-B hepatitis. Through recently developed diagnostic assays, routine serologic screening of blood donors has prevented most cases of posttransfusion hepatitis. The purpose of this paper is to comprehensively review current information regarding the virology of HCV. Recent findings on the genome organization, its relationship to other viruses, the replication of HCV ribonucleic acid, HCV translation, and HCV polyprotein expression and processing are discussed. Also reviewed are virus assembly and release, the variability of HCV and its classification into genotypes, the geographic distribution of HCV genotypes, and the biologic differences between HCV genotypes. The assays used in HCV genotyping are discussed in terms of reliability and consistency of results, and the molecular epidemiology of HCV infection is reviewed. These approaches to HCV epidemiology will prove valuable in documenting the spread of HCV in different risk groups, evaluating alternative (nonparenteral) routes of transmission, and in understanding more about the origins and evolution of HCV.

Genome, Viral↗

PubMed2004

Antiretroviral therapy in HIV infection: are neurologically active drugs important?

BACKGROUND: The effect on neuropsychological function of antiretroviral drugs that are able to penetrate into the brain in effective concentration (neuroactive drugs) remains unclear. OBJECTIVE: To investigate whether highly active antiretroviral therapy (HAART) containing neuroactive drugs is associated with better neuropsychological performance in patients with human immunodeficiency virus disease. DESIGN: Cross-sectional survey. SETTING: Tertiary referral hospital outpatient clinics. PATIENTS: The study population consisted of 97 individuals positive for human immunodeficiency virus (stage C3, 1993 Centers for Disease Control and Prevention classification) whose condition had been stable on their current HAART regimen for a mean +/- SD of 18.5 +/- 16.5 months and who were aged 48.14 +/- 9.38 years. The patient groups were analyzed according to whether their regimen contained 3 or more neuroactive drugs (neuroHAART group; n = 41) or not (HAART group; n = 56). Thirty seronegative men matched for age and education were recruited as controls. MAIN OUTCOME MEASURE: Neuropsychological performance on 7 cognitive domains. RESULTS: The neuroHAART and HAART groups did not differ from one another on neuropsychological performance, but both patient groups were impaired compared with controls. Impaired patients in each treatment group were compared, and the neuroHAART group showed significantly better memory performance, unrelated to plasma viral load, than the HAART group. CONCLUSION: No direct benefit of neuroactive HAART therapy was found in patients with advanced human immunodeficiency virus infection. However, in neuropsychologically impaired patients, there was a benefit in memory function. This suggests that a threshold of neuropsychological impairment is required for the benefit of neuroactive HAART.

Adult↗

PubMed1992

Comparison of a dengue-2 virus and its candidate vaccine derivative: sequence relationships with the flaviviruses and other viruses.

A comparison of the sequence of the dengue-2 16681 virus with that of the candidate vaccine strain (16681-PDK53) derived from it identified 53 of the 10,723 nucleotides which differed between the strains. Nucleotide changes occurred in genes coding for all virion and nonvirion proteins, and in the 5' and 3' untranslated regions. Twenty-seven of the nucleotide changes resulted in amino acid alterations. The greatest amino acid sequence differences in the virion proteins occurred in prM (2.20%; 2/91 amino acids) followed by the M protein (1.33%; 1/75 amino acids), the C protein (0.88%; 1/114 amino acid), and the E protein (0.61%; 3/495 amino acids). Differences in the amino acid sequence of nonvirion proteins ranged from 1.51% (6/398 amino acids) in NS4 to 0.33% (3/900 amino acids) in NS5. The encoded protein sequences of 16681-PDK53 were also compared with the published sequences of other flaviviruses to obtain a detailed classification of 17 flaviviruses using the neighbor-joining tree method. The analyses of the sequence data produced dendrograms which supported the traditional groupings based on serological evidence, and they suggested that the flaviviruses have evolved by divergent mutational change and there was no evidence of genetic recombination between members of the group. Comparisons of the sequences of the flavivirus polymerase and helicase-like proteins (NS5 and NS3, respectively) with those from other viruses yielded a classification of the flaviviruses indicating that the primary division of the flaviviruses was between those transmitted by mosquitoes and those transmitted by ticks.

Amino Acid Sequence↗

PubMed1998

The simian T-lymphotropic virus STLV-PP1664 from Pan paniscus is distinctly related to HTLV-2 but differs in genomic organization.

We have isolated a highly divergent simian T-lymphotropic virus, STLV-PP1664, from a wild-caught bonobo (Pan paniscus). Previous phylogenetic analysis suggested that this virus represents an additional type of STLV but this has now become a matter of discussion. We have now obtained and analyzed the entire genome of STLV-PP1664. All major genes and their corresponding viral messengers were identified. Sequence comparison and phylogenetic analysis indicated that this virus, together with the closely related panp isolate, belongs to an early lineage within the PTLV-2 clade, differing from HTLV-2 by about 25%. In contrast to the HTLV-1 and HTLV-2 LTR, only two 21-bp repeats instead of three were found in the STLV-PP1664 LTR. Additional messengers, resulting from alternative splicing, potentially encode five different accessory proteins from open reading frames in the pX region: prorfI, porfII, ptorfV', and two isoforms of Rex. The amino acid sequences of these proteins are only distinctly related to the accessory proteins from HTLV-2. These data suggest a different genomic organization of the STLV-PP1664 pX region than that of HTLV-2. We conclude that STLV-PP1664, although related to HTLV-2, has some distinct features in the LTR and the pX regions, the impact of which needs further investigation. Although arguments pro and contra a distinct classification are nearly equally balanced, we propose to classify this virus as an STLV-2, designated STLV-2PP1664.

Amino Acid Sequence↗

PubMed1991

Detection of Epstein-Barr virus DNA in formalin-fixed paraffin-embedded tissue of nasopharyngeal carcinoma using polymerase chain reaction and in situ hybridization.

The polymerase chain reaction method for amplification of DNA in formalin-fixed, paraffin-embedded tissue sections was used to detect Epstein-Barr virus DNA in nasopharyngeal carcinomas from Japanese patients. Thirty-one cases of nasopharyngeal carcinoma and 8 cases of lymph node metastasis of nasopharyngeal carcinoma were studied. Detection rates of Epstein-Barr virus in various types of nasopharyngeal carcinoma according to the World Health Organization classification were as follows: 10 of 10 undifferentiated carcinomas, 8 of 13 nonkeratinizing carcinomas, and 5 of 7 keratinizing carcinomas. Eight lymph node metastases, for which the primary was positive for Epstein-Barr virus, also contained Epstein-Barr virus DNA. By in situ hybridization using a biotinylated Epstein-Barr virus probe, it was clearly demonstrated that Epstein-Barr virus DNA was localized in the nuclei of the neoplastic cells. The clinical features of nasopharyngeal carcinoma with or without Epstein-Barr virus were not different. These results demonstrate that nasopharyngeal carcinoma in Japanese patients is closely associated with Epstein-Barr virus infection, similar to nasopharyngeal carcinoma of other endemic and nonendemic areas.

Carcinoma↗

PubMed1999

[Hepatitis C: natural history, biology, treatment monitoring].

This article presents the laboratory tests used to diagnose hepatitis C, to evaluate the severity of the chronic fibrosing disease, and to monitor the efficacy of treatment. Histological examination of liver biopsies is of the utmost importance for evaluating the development of fibrosis. Factors that precipitate fibrosis are reviewed. The annual rate of fibrosis progression can be assessed based on the estimated duration of hepatitis C virus contamination and on the fibrosis score established using the METAVIR classification. This allows to distinguish slow, fast, and intermediate fibrosis and to estimate the mean time to cirrhosis development. Combined use of interferon alpha (3 million units three times a week) and of Ribavirine (1000-1200 mg per day orally according to body weight) for 6 to 12 months is currently the standard treatment for hepatitis C. Treatment efficacy varies with a number of virus-related factors (genotype, viral burden) and patient-related factor (hepatic fibrosis, age, sex). In nonresponders, the value of treatment should not be assessed in terms of efficacy but in terms of slowing of fibrosis progression.

Antiviral Agents↗

PubMed2000

Cloning and sequencing of columbid circovirus (coCV), a new circovirus from pigeons.

The complete nucleotide sequence of columbid circovirus (CoCV) isolated from pigeons is described. CoCV was amplified using a consensus primer PCR approach directed against conserved sequences within the rep genes of vertebrate circoviruses. The genome of CoCV is circular and 2037 nt in size. It displays 55% homology to the genome of psittacine beak and feather disease virus and is more distantly related (< 40% homology) to porcine circovirus type 1 and 2. Two major open reading frames were identified, encoding the replicase and the putative capsid protein of CoCV. A region similar to the origin of replication of other circoviruses was found: it encompasses a stem-loop structure with the nonamer 5'-TAGTATTAC, conserved in circo-, nano- and geminiviruses. Phylogenetic analyses suggest classification of CoCV as member of the genus Circovirus of the virus family Circoviridae.

Amino Acid Sequence↗

PubMed1980

The relationship of certain tymoviruses assessed from the amino acid composition of their coat proteins.

The amino acid composition of the coat proteins of the following viruses is reported: Andean potato latent, clitoria yellow vein, desmodium yellow mottle, dulcamara mottle, eggplant mosaic, okra mosaic, ononis yellow mosaic, scrophularia mottle, and, as controls, cocksfoot mild mosaic and cocksfoot mottle viruses. These data, together with some already published, were used to compute classifications of the tymoviruses. These classifications show a general similarity to Koenig's serological classification of the tymoviruses, but the correlation is poor, unlike similar comparisons of tobamovirus classifications. Several possible reasons for the poor correlation have been examined and excluded, and its implications are discussed.

Amino Acids↗

PubMed2003

Epidemiologic classification of human papillomavirus types associated with cervical cancer.

BACKGROUND: Infection with human papilloma virus (HPV) is the main cause of cervical cancer, but the risk associated with the various HPV types has not been adequately assessed. METHODS: We pooled data from 11 case-control studies from nine countries involving 1918 women with histologically confirmed squamous-cell cervical cancer and 1928 control women. A common protocol and questionnaire were used. Information on risk factors was obtained by personal interviews, and cervical cells were collected for detection of HPV DNA and typing in a central laboratory by polymerase-chain-reaction-based assays (with MY09/MY11 and GP5+/6+ primers). RESULTS: HPV DNA was detected in 1739 of the 1918 patients with cervical cancer (90.7 percent) and in 259 of the 1928 control women (13.4 percent). With the GP5+/6+ primer, HPV DNA was detected in 96.6 percent of the patients and 15.6 percent of the controls. The most common HPV types in patients, in descending order of frequency, were types 16, 18, 45, 31, 33, 52, 58, and 35. Among control women, types 16, 18, 45, 31, 6, 58, 35, and 33 were the most common. For studies using the GP5+/6+ primer, the pooled odds ratio for cervical cancer associated with the presence of any HPV was 158.2 (95 percent confidence interval, 113.4 to 220.6). The odds ratios were over 45 for the most common and least common HPV types. Fifteen HPV types were classified as high-risk types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, and 82); 3 were classified as probable high-risk types (26, 53, and 66); and 12 were classified as low-risk types (6, 11, 40, 42, 43, 44, 54, 61, 70, 72, 81, and CP6108). There was good agreement between our epidemiologic classification and the classification based on phylogenetic grouping. CONCLUSIONS: In addition to HPV types 16 and 18, types 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, and 82 should be considered carcinogenic, or high-risk, types, and types 26, 53, and 66 should be considered probably carcinogenic.

Adenocarcinoma↗

PubMed1987

The classification of tymoviruses by cDNA-RNA hybridization and other measures of relatedness.

The relationships of twelve tymoviruses have been assessed by cDNA-RNA hybridization. In addition, the percentage molar nucleotide composition of the genome of the PD strain of Kennedya yellow mosaic virus and the percentage molar amino acid composition of the coat proteins of cacao yellow mosaic, Kennedya yellow mosaic and turnip yellow mosaic (Cardamine strain) viruses were estimated. These as well as published serological comparisons and genome and coat protein composition determinations were used to compute classifications of tymoviruses using various "metrics", and simple numerical methods were used to compare the classifications. Measures of relatedness estimated from cDNA-RNA hybridization and base ratio data correlated significantly with each other, but were less closely correlated with those calculated from amino acid data, and did not correlate with those calculated from serological tests. The serological relationships correlated significantly with estimates of relatedness calculated from amino acid data, but not with those based on hybridization or base ratio data. The differences between these classifications mostly resulted from the anomalous behaviour of eggplant mosaic virus, its particles are serologically close to those of other tymoviruses that naturally infect species of the tobacco family, whereas in cDNA-RNA hybridization tests eggplant mosaic virus is closest to the tymoviruses that infect legumes. Similar but smaller anomalies in the characteristics of other tymoviruses were also found.

Amino Acids↗