Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 21
Filter
1.
Respiration ; 75(2): 155-7, 2008.
Article in English | MEDLINE | ID: mdl-17124380

ABSTRACT

BACKGROUND: Pulmonary hypertension is a severe pulmonary vascular disease leading to rapid deterioration and death. Histological and clinical evidence suggests that smooth muscle proliferation is part of the pathogenesis of the disease. Human herpesvirus 8 (HHV-8) is a gamma-herpesvirus that is implicated in malignancies and in Kaposi's sarcoma. Recently, the association of HHV-8 with idiopathic pulmonary arterial hypertension (PAH) has been found. OBJECTIVE: The aim of this study was to investigate the presence of HHV-8 in the lung tissue of Israeli patients with PAH. METHOD: The presence of HHV-8 sequences was investigated by polymerase chain reaction examination in 6 biopsies of patients with pulmonary hypertension. Three patients had idiopathic pulmonary hypertension, 2 patients pulmonary venoocclusive disease, and 1 patient pulmonary hypertension associated with mixed connective tissue disease. RESULT: We did not find any association between HHV-8 and PAH in these Israeli patients, as all the samples were negative for polymerase chain reaction. CONCLUSION: Our findings, together with the epidemiological data of HHV-8 prevalence and incidence rates of Kaposi's sarcoma and PAH in Israel, provide further evidence which argues against an association between HHV-8 infection and PAH.


Subject(s)
DNA, Viral/isolation & purification , Herpesvirus 8, Human/isolation & purification , Hypertension, Pulmonary/virology , Adolescent , Adult , Biopsy , Female , Herpesvirus 8, Human/genetics , Humans , Israel , Male , Middle Aged , Viral Proteins/genetics
3.
Br J Cancer ; 89(9): 1657-60, 2003 Nov 03.
Article in English | MEDLINE | ID: mdl-14583765

ABSTRACT

Trends in the incidence of classic Kaposi's sarcoma in the Jewish population in Israel for the period between 1960 and 1998 were analysed. World standardised incidence rates of 20.7 and 7.5 per million among men and women, respectively, were calculated. The highest incidence rates were displayed by men originated from Africa and by Asian-born women.


Subject(s)
Jews , Sarcoma, Kaposi/epidemiology , Adolescent , Adult , Age Factors , Aged , Child , Child, Preschool , Emigration and Immigration , Female , Herpesviridae Infections/epidemiology , Herpesvirus 8, Human , Humans , Incidence , Infant , Infant, Newborn , Israel , Male , Middle Aged , Multivariate Analysis , Registries , Regression Analysis , Risk Factors , Sarcoma, Kaposi/ethnology , Sex Factors
4.
Cell Death Differ ; 8(12): 1224-31, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11753570

ABSTRACT

Sindbis virus (SV) is an alphavirus used as a model for studying the pathogenesis of viral encephalitis. In this study we examined the effects and the mechanisms involved in the apoptosis induced by SV in PC-12 cells, and the role of a vFLIP in this process. Infection of PC-12 cells with a neurovirulent strain of SV, SVNI, induced cell apoptosis. Overexpression of vFLIP encoded by the HHV-8 or treatment with a caspase-8 inhibitor inhibited cell apoptosis. SVNI induced an increase in the expression of tumor necrosis factor alpha (TNF-alpha), and pre-treatment of the cells with an anti-TNF-alpha blocking antibody or with soluble TNF-alpha receptor abrogated the apoptotic effect of SVNI. Moreover, TNF-alpha R1 knockout mice were more resistant to the cytopathic effects of the virus as compared to control animals. Our results indicate that the apoptosis induced by SVNI is mediated by activation of caspase-8, and that TNF-alpha plays an important role in the apoptotic response.


Subject(s)
Apoptosis , Intracellular Signaling Peptides and Proteins , Tumor Necrosis Factor-alpha/physiology , Animals , Antibodies, Monoclonal , CASP8 and FADD-Like Apoptosis Regulating Protein , Carrier Proteins , Caspase 8 , Caspase 9 , Caspases/metabolism , Gene Expression , Mice , PC12 Cells , RNA, Messenger/biosynthesis , Rats , Sindbis Virus/physiology , Virus Replication
5.
Leuk Lymphoma ; 41(3-4): 439-43, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11378560

ABSTRACT

Primary effusion lymphoma (PEL) is a recently described rare type of non-Hodgkin's lymphoma occurring almost exclusively in HIV infected people. Human herpesvirus 8 (HHV-8), has been linked with PEL, and a causative relationship has been suggested. In the vast majority of PEL cases Epstein-Barr virus (EBV) has been found in the tumour cells. We describe here an elderly human immune deficiency (HIV) seronegative man with intractable chest pain and pleural effusion. The diagnosis of malignant lymphoma was suggested cytologically and confirmed histologically following pleural biopsy. No lymphadenopathy or organ involvement with lymphoma was found. Systemic chemotherapy with a modified CHOP regimen with G-CSF support gradually led to the resolution of the chest pain and ultimately resulted in a complete clinical remission (CCR). The presence of HHV-8 was demonstrated by PCR using paraffin-embedded tissue samples from the involved pleura, whereas EBV-associated genetic material was absent. The patient remained in CCR for 18 months and died of an unrelated cause (cerebrovascular event). Only 11 other cases with clinical and virological features similar to those of our patient have been reported in the literature. Analysis of these rare cases suggests HIV-negative EBV-negative PEL to be a distinct clinical entity with epidemiological features resembling classical KS and supports an EBV-independent role for HHV-8 in the pathogenesis of PEL.


Subject(s)
Lymphoma, Non-Hodgkin/etiology , Aged , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Chest Pain , Cyclophosphamide/administration & dosage , DNA, Viral/blood , Doxorubicin/administration & dosage , Granulocyte Colony-Stimulating Factor/administration & dosage , HIV Seronegativity , Herpesvirus 8, Human/genetics , Humans , Lymphoma, Non-Hodgkin/drug therapy , Lymphoma, Non-Hodgkin/virology , Male , Pleural Effusion, Malignant/drug therapy , Pleural Effusion, Malignant/etiology , Pleural Effusion, Malignant/virology , Prednisone/administration & dosage , Remission Induction , Vincristine/administration & dosage
6.
Clin Infect Dis ; 32(10): 1502-5, 2001 May 15.
Article in English | MEDLINE | ID: mdl-11317254

ABSTRACT

Human herpesvirus-8 (HHV-8) DNA was identified in kidney allografts in 2 of 3 transplant recipients prior to the development of Kaposi's sarcoma, and increase in viral antibody titer was found in the third. Combined genotypic and serologic analyses could be used to identify patients at risk and suggest that the kidney may be a site of HHV-8 latency.


Subject(s)
DNA, Viral/analysis , Herpesvirus 8, Human/isolation & purification , Kidney Transplantation , Kidney/virology , Transplants/virology , Adult , Biopsy , Herpesvirus 8, Human/genetics , Humans , Male , Middle Aged , Sarcoma, Kaposi/virology , Transplantation, Homologous
7.
J Infect Dis ; 182(1): 306-10, 2000 Jul.
Article in English | MEDLINE | ID: mdl-10882613

ABSTRACT

Kaposi's sarcoma (KS)-associated herpesvirus open-reading frame (ORF) 73 encodes a latency-associated nuclear antigen (LANA) that is the basis for several serologic assays. Immunoreactive epitopes were searched for by peptide mapping, and 171 cleavable, biotinylated 17-mer peptides offset by 5 residues were synthesized and screened with human serum samples by ELISA. The initial screen, which used highly reactive serum diluted 1:500, identified 38 immunoreactive peptides. These were subsequently tested on additional serum samples diluted 1:40. Thirteen peptides were more reactive with serum samples from patients with KS than with control serum samples. No single epitope was recognized by most KS patient serum samples. Combined use of these peptides did not increase test sensitivity to that of current indirect immunofluorescence assays for LANA (80%-90%). For comparison, full-length ORF73 was expressed in bacteria and analyzed by Western blot. The overall sensitivity was 67% (range, 100% among US patients with classic KS to 52% among Italian patients with classic KS). These studies suggest that LANA immunoreactivity may be due to variations in patient response or conformational epitopes.


Subject(s)
Herpesvirus 8, Human/isolation & purification , Nuclear Proteins/analysis , Sarcoma, Kaposi/diagnosis , Antigens, Viral , Blotting, Western , Epitope Mapping , Evaluation Studies as Topic , Herpesviridae Infections/diagnosis , Herpesvirus 8, Human/genetics , Herpesvirus 8, Human/immunology , Humans , In Vitro Techniques , Nuclear Proteins/blood , Nuclear Proteins/genetics , Nuclear Proteins/immunology , Peptide Mapping , Recombinant Proteins/analysis , Sarcoma, Kaposi/blood , Sarcoma, Kaposi/immunology , Sarcoma, Kaposi/virology
8.
Cancer ; 88(3): 500-17, 2000 Feb 01.
Article in English | MEDLINE | ID: mdl-10649240

ABSTRACT

BACKGROUND: Although Kaposi sarcoma (KS) initially was described over a century ago, its biology remains enigmatic and conflicting. Whereas the classic type occurs mainly in older men of Mediterranean or Eastern European backgrounds and is not linked to impairment of the host immune response, iatrogenic and human immunodeficiency virus (HIV)-associated KS are linked to such conditions. A recently discovered pathogen, KS-associated herpesvirus (KSHV) (also known as human herpesvirus 8 [HHV8]), is found in tissues from all four forms of KS (classic, iatrogenic, endemic [African], and HIV-associated). This universal detection of KSHV/HHV8 suggests a central role for the virus in the development of KS and a common etiology for all KS types. The epidemiology and risk factors of classic KS, along with the biology of KSHV/HHV8 and the prevalence of the virus among different populations, is presented. METHODS: The current review is based on multiple information sources, electronic health data in all languages from 1966 onward, and previously published scientific reports from the Americas, Europe, and Africa. RESULTS: Nearly 5000 cases of morphologically characterized classic KS have been reported in Europe, Mediterranean countries, and the Americas up to 1998. Geographic location, ethnicity, time interval, age, and gender heavily influence the incidence rate of classic KS. The rate of incidence of nonacquired immunodeficiency syndrome-associated KS correlates with the KSHV/HHV8 seroprevalence in the general population. CONCLUSIONS: Many contributory factors undoubtedly have etiologic and pathogenic significance in the development of classic KS; however, the interplay between these factors has complicated the understanding of the induction and development of the disease as well as the significance of each factor. As with other cell-transforming human DNA viruses, infection with KSHV/HHV8 alone is not sufficient for the development of KS and additional cofactors are required.


Subject(s)
Sarcoma, Kaposi/epidemiology , Adolescent , Adult , Africa/epidemiology , Age Factors , Aged , Aged, 80 and over , Americas/epidemiology , Child , Cocarcinogenesis , Ethnicity/statistics & numerical data , Europe/epidemiology , Female , Herpesvirus 8, Human/physiology , Humans , Incidence , Male , Middle Aged , Prevalence , Risk Factors , Sarcoma, Kaposi/virology , Sex Factors
9.
FEBS Lett ; 461(3): 189-95, 1999 Nov 19.
Article in English | MEDLINE | ID: mdl-10567695

ABSTRACT

The MUC1 gene encodes a mucin glycoprotein and is overexpressed in breast cancer. Knowledge of the mechanisms leading to MUC1 overexpression may help in the development of molecular approaches for breast cancer therapy. In order to study the regulation of the MUC1 gene transcription, we analyzed functional activities of various deletion mutants of the MUC1 promoter. We established that transcriptional cis-elements present in the SacI/XmnI fragment of the promoter are competent and sufficient for expression of, at least, tandem repeats containing isoform(s) of the MUC1 protein. CAT transfection analysis showed that both the 3' and 5' regions of the SacI/XmnI fragment possess transcription activities. Promoter activities associated with the SacI/XmnI fragment were confirmed by a RNase protection assay, which demonstrated multiple transcription start sites (TSSs) in the MUC1 gene transcribed in epithelial T47D cells. We show that treatment of the T47D cells with TGFbeta1 leads to activation of additional TSSs in the MUC1 gene. The roles of the structural and functional properties of the MUC1 promoter in MUC1 gene transcription are discussed.


Subject(s)
Adenocarcinoma/genetics , Breast Neoplasms/genetics , Gene Expression Regulation, Neoplastic , Mucin-1/genetics , Neoplasm Proteins/genetics , Promoter Regions, Genetic , Adenocarcinoma/metabolism , Base Sequence , Breast Neoplasms/metabolism , Chloramphenicol O-Acetyltransferase/biosynthesis , DNA, Neoplasm/genetics , DNA, Neoplasm/metabolism , Female , Humans , Molecular Sequence Data , Mucin-1/biosynthesis , Neoplasm Proteins/biosynthesis , Recombinant Fusion Proteins/biosynthesis , Sequence Deletion , Transcription Factors/metabolism , Transcription, Genetic , Transfection
10.
Cancer Res ; 59(19): 4984-9, 1999 Oct 01.
Article in English | MEDLINE | ID: mdl-10519412

ABSTRACT

Kaposi's sarcoma-associated herpesvirus (KSHV) has a key etiological role in development of Kaposi's sarcoma (KS). v-Cyclin is a KSHV-encoded homologue to D-type cyclins that associates with cellular cyclin-dependent kinase 6 (CDK6). v-Cyclin promotes S-phase entry of quiescent cells and has been suggested to execute functions of both D- and E-type cyclins. In this study, expression of v-cyclin in cells with elevated levels of CDK6 led to apoptotic cell death after the cells entered S phase. The cell death required the kinase activity of CDK6 because cells expressing a kinase-deficient form of CDK6 did not undergo apoptosis upon v-cyclin expression. Studies on the mechanisms involved in this caspase-3-mediated apoptosis indicated that it was independent of cellular p53 or pRb status, and it was not suppressed by Bcl-2. In contrast, the KSHV-encoded v-Bcl-2 efficiently suppressed v-cyclin-/CDK6-induced apoptosis, demonstrating a marked difference in the antiapoptotic properties of c-Bcl-2 and v-Bcl-2. In KS lesions, high CDK6 expression was confined to a subset of cells, some of which displayed signs of apoptosis. These results suggest that v-cyclin may exert both growth-promoting and apoptotic functions in KS, depending on factors regulating CDK6 and v-Bcl-2 levels.


Subject(s)
Apoptosis/physiology , Cyclin-Dependent Kinases , Cyclins/genetics , Cyclins/metabolism , Herpesvirus 8, Human/genetics , Protein Serine-Threonine Kinases/metabolism , Sarcoma, Kaposi/pathology , Animals , Apoptosis/drug effects , Bone Neoplasms , Caspase 3 , Caspases/metabolism , Cell Line , Cyclin-Dependent Kinase 6 , Cysteine Proteinase Inhibitors/pharmacology , Enzyme Inhibitors/pharmacology , Herpesvirus 8, Human/physiology , Humans , Molecular Sequence Data , Oligopeptides/pharmacology , Osteosarcoma , Proto-Oncogene Proteins c-bcl-2/metabolism , Retinoblastoma Protein/metabolism , Sarcoma, Kaposi/enzymology , Staurosporine/pharmacology , Tumor Cells, Cultured , Viral Proteins
12.
J Virol ; 73(2): 1438-46, 1999 Feb.
Article in English | MEDLINE | ID: mdl-9882349

ABSTRACT

Retinoblastoma tumor suppressor protein (pRB) inhibition by tumor virus oncoproteins has been attributed to the need for these viruses to promote lytic viral nucleic acid synthesis by unscheduled entry into the S phase of the cell cycle. Kaposi's sarcoma-associated herpesvirus (KSHV or HHV8) encodes a functional cyclin (vCYC) which is expressed during latency and can direct phosphorylation of pRB. We mapped the two major latent transcripts encoding vCYC, latent transcript 1 (LT1) and LT2, by cDNA sequencing, 5' rapid amplification of cDNA ends, and primer extension analyses. Both LT1 and LT2 transcripts are spliced, originate from the same start site, and encode ORF K13 (vFLIP) as well as ORF72 (vCYC). The latency-associated nuclear antigen (LANA, ORF73) is encoded by LT1 but spliced from LT2. While differential expression of the two transcripts was not found, the promoter controlling LT1/LT2 transcription is regulated in a cell cycle-dependent manner. Activities of both KSHV LT1/LT2 and huCYC D1 luciferase promoter reporters transfected into NIH 3T3 cells increase 11- and 4-fold, respectively, after release from cell cycle arrest by serum starvation. Further, vCYC and huCYC D2 mRNA levels are low in naturally infected BCBL-1 cells arrested in late G1 with L-mimosine but increase in parallel during a 24-h period after release from cell cycle arrest. Cell cycle regulation of KSHV vCYC expression mimics cellular D cyclin regulation and may maintain infected cell cycling. This is consistent with an alternative hypothesis that tumor viruses have developed specific responses to innate cellular defenses against latent virus infection that include pRB-induced cell cycle arrest.


Subject(s)
Genes, Viral , Herpesvirus 8, Human/genetics , Promoter Regions, Genetic , Sarcoma, Kaposi/virology , 3T3 Cells , Animals , Base Sequence , Blotting, Northern , Cell Cycle , Cell Line, Transformed , Chromosome Mapping , DNA, Viral , Genes, Reporter , HeLa Cells , Herpesvirus 8, Human/physiology , Humans , Luciferases/genetics , Mice , Molecular Sequence Data , Virus Latency
13.
J Virol ; 72(2): 1005-12, 1998 Feb.
Article in English | MEDLINE | ID: mdl-9444993

ABSTRACT

Kaposi's sarcoma-associated herpesvirus (KSHV) gene transcription in the BC-1 cell line (KSHV and Epstein-Barr virus coinfected) was examined by using Northern analysis with DNA probes extending across the viral genome except for a 3-kb unclonable rightmost region. Three broad classes of viral gene transcription have been identified. Class I genes, such as those encoding the v-cyclin, latency-associated nuclear antigen, and v-FLIP, are constitutively transcribed under standard growth conditions, are unaffected by tetradecanoylphorbol acetate (TPA) induction, and presumably represent latent viral transcripts. Class II genes are primarily clustered in nonconserved regions of the genome and include small polyadenylated RNAs (T0.7 and T1.1) as well as most of the virus-encoded cytokines and signal transduction genes. Class II genes are transcribed without TPA treatment but are induced to higher transcription levels by TPA treatment. Class III genes are primarily structural and replication genes that are transcribed only following TPA treatment and are presumably responsible for lytic virion production. These results indicate that BC-1 cells have detectable transcription of a number of KSHV genes, particularly nonconserved genes involved in cellular signal transduction and regulation, during noninduced (latent) virus culture.


Subject(s)
Genes, Viral , Genome, Viral , Herpesvirus 8, Human/genetics , Lymphoma/virology , Humans , Signal Transduction , Transcription, Genetic , Tumor Cells, Cultured
14.
Methods Mol Med ; 10: 227-35, 1998.
Article in English | MEDLINE | ID: mdl-21374233

ABSTRACT

Herpes simplex virus (HSV) amplicons are defective virus vectors capable of introducing amplified foreign genes into variable types of eukaryotic cells, such as fibroblasts, macrophages, glia, and neurons in different organisms including rodents, monkeys, and human (refs. 1-3; reviewed in ref. 4). The defective viruses follow their nondefective counterparts in the ability to infect mitotic, as well as postmitotic cells. This makes them potentially useful vectors for use in nondividing cells, such as in nerve cells. Available retrovirus vectors employed to date for gene therapy require cell division and therefore cannot be used to target neurons.

15.
J Virol ; 71(8): 5915-21, 1997 Aug.
Article in English | MEDLINE | ID: mdl-9223481

ABSTRACT

Kaposi's sarcoma (KS)-associated herpesvirus or human herpesvirus 8 (KSHV/HHV8) is the likely cause of KS and primary effusion lymphomas or body cavity-based lymphomas (BCBLs). A latency-associated nuclear immunofluorescence antigen (LANA) (D. H. Kedes, E. Operskalski, M. Busch, R. Kohn, J. Flood, and D. Ganem, Nat. Med. 2:918-924, 1996; S. J. Gao, L. Kingsley, M. Li, W. Zheng, C. Parravicini, J. Ziegler, R. Newton, C. R. Rinaldo, A. Saah, J. Phair, R. Detels, Y. Chang, and P. S. Moore, Nat. Med. 2:925-928, 1996) and a 222- to 234-kDa nuclear protein (LNA) (S. J. Gao, L. Kingsley, D. R. Hoover, T. J. Spira, C. R. Rinaldo, A. Saah, J. Phair, R. Detels, P. Parry, Y. Chang, and P. S. Moore, N. Engl. J. Med. 335:233-241, 1996) have previously been described in BCBL cell lines by immunofluorescence and Western blotting techniques, respectively. To identify the viral gene(s) encoding this antigen(s) we screened a cDNA library from HBL-6 cells, a B-cell lymphoma cell line persistently infected with KSHV/HHV8, with KS patient sera. One set of positive clones contained the 3' end of orf73, as well as the complete orf72 and orfK13, and another set contained the 5' end of orf73. Comparison of cDNA sequences with the KSHV/HHV8 genomic sequence revealed a splice event, occurring upstream of orf73. Immunoaffinity purified antibodies to a recombinant carboxy-terminal fragment of the orf73-encoded protein showed the characteristic speckled nuclear immunofluorescence pattern of LANA and reacted with the 222- to 234-kDa LNA on Western blots. Expression of full-length orf73 in bacteria and COS7 cells reproduced the LNA banding pattern. Immunohistochemistry on cases of nodular KS revealed that orf73/LNA is expressed in the nucleus of KS spindle cells. These findings demonstrate that orf73 encodes the 222- to 234-kDa LNA, is a component of LANA, and is expressed in KS tumor cells.


Subject(s)
Antigens, Nuclear/genetics , Herpesvirus 8, Human/genetics , Nuclear Proteins/genetics , Open Reading Frames , Viral Proteins/genetics , Animals , Antigens, Nuclear/physiology , Blotting, Western , COS Cells , DNA, Complementary/analysis , Fluorescent Antibody Technique , Herpesvirus 8, Human/chemistry , Molecular Weight , Nuclear Proteins/physiology , Sarcoma, Kaposi/virology , Viral Proteins/physiology
16.
Nat Med ; 3(3): 293-8, 1997 Mar.
Article in English | MEDLINE | ID: mdl-9055856

ABSTRACT

Kaposi's sarcoma-associated herpesvirus (KSHV) is a newly discovered herpesvirus etiologically associated with Kaposi's sarcoma (KS) and two lymphoproliferative disorders. We describe a KSHV vbcl-2 gene with homology to the proto-oncogene bcl-2. It is expressed in KS lesions and in cell lines derived from primary effusion lymphomas. Using yeast and human cells we demonstrate the ability of KSHV vBcl-2 protein to suppress Bax toxicity. We show that KSHV vBcl-2 heterodimerizes with human Bcl-2 in a yeast two-hybrid system. These results suggest that KSHV vBcl-2 plays an anti-apoptotic role in virus infected cells.


Subject(s)
Genes, Viral , Herpesvirus 8, Human/genetics , Proto-Oncogene Proteins c-bcl-2/genetics , Amino Acid Sequence , Gene Expression , Humans , Molecular Sequence Data , Proto-Oncogene Mas , Sequence Analysis , Sequence Homology, Amino Acid
17.
Virology ; 208(2): 789-94, 1995 Apr 20.
Article in English | MEDLINE | ID: mdl-7747452

ABSTRACT

We analyzed the long terminal repeat (LTR) of the lymphoproliferative disease virus of turkeys for sequences that influence its promoter activity by using the chloramphenicol acetyltransferase assay. A series of LTR deletion mutants and recombinants between LTR and simian virus 40 regulatory sequences were used for these studies. Through transfection experiments, we identified a negative regulatory element residing at the 5' end of the U3. The two imperfect direct repeats (DRs) located at nt - 170 to - 125 upstream of the RNA transcription site were identified as enhancer elements which could stimulate transcription of a heterologous promoter in an orientation independent manner. Specific interaction of nuclear factors with the DRs element was identified. The two DRs contain cArg motifs which are suggested to play a role in tissue specific expression of several cellular genes.


Subject(s)
Alpharetrovirus/genetics , Repetitive Sequences, Nucleic Acid/genetics , Transcription, Genetic/genetics , Turkeys/virology , Animals , Base Sequence , Cell Line , Chloramphenicol O-Acetyltransferase/biosynthesis , Chloramphenicol O-Acetyltransferase/genetics , DNA, Viral/metabolism , DNA-Binding Proteins/metabolism , Gene Expression Regulation, Viral/genetics , Molecular Sequence Data , Promoter Regions, Genetic/genetics , Recombinant Fusion Proteins/biosynthesis , Sequence Deletion/physiology , Simian virus 40/genetics , Transfection
18.
Virology ; 204(2): 680-91, 1994 Nov 01.
Article in English | MEDLINE | ID: mdl-7941337

ABSTRACT

The lymphoproliferative disease retrovirus (LPDV) induces an acute, horizontally transmitted disease of turkeys that is often fatal. Although LPDV cannot be grown in cultured cells, it was possible to isolate molecular clones of biologically active integrated proviral genomes from spleens of infected turkeys. Based upon molecular hybridization and nucleotide sequence comparisons of its pol gene, LPDV was shown to represent a distinct group of avian retroviruses most closely related to avian sarcoma-leukemia viruses. Here we report the complete nucleotide sequence of the LPDV genome as well as amino acid sequence analysis of its gag gene products. The genetic organization of LPDV is characteristic of members of the oncovirus subfamily. Further sequence comparisons of the gag gene confirmed that LPDV is most closely related to Rous sarcoma virus (RSV). However, the gag, pro, and pol open reading frames (ORFs) were in different translational phases so that the expression of their mature gene products would require the double frame-shifting mechanism utilized by simian retroviruses, mouse mammary tumor virus, and human T-cell leukemia virus. In contrast, the RSV proteinase is synthesized as part of the gag precursor. The LPDV gag gene differs from that of RSV as well as from all other retroviruses in that it encodes a unique 31,000-Da (p31) protein, located between the MA and the CA coding sequences. FOur short ORFs of unknown function were present, Whether the putative products of these ORFs account for the acute nature of LPDV-induced disease remains to be determined.


Subject(s)
Genome, Viral , Lymphoproliferative Disorders/veterinary , Poultry Diseases/virology , Retroviridae/genetics , Turkeys/virology , Amino Acid Sequence , Animals , Base Sequence , Gene Products, env/genetics , Gene Products, gag/genetics , Gene Products, pol/genetics , Lymphoproliferative Disorders/virology , Molecular Sequence Data , Open Reading Frames , Repetitive Sequences, Nucleic Acid
19.
Am J Vet Res ; 55(6): 769-72, 1994 Jun.
Article in English | MEDLINE | ID: mdl-7944012

ABSTRACT

Lymphoproliferative disease virus, a type-C retrovirus, is the etiologic agent of a naturally acquired lymphoproliferative disorder in turkeys. The disease is characterized by rapid induction of lymphoproliferative lesions with morphologic and histopathologic features resembling those of reticuloendotheliosis. Owing to lack of overt clinical manifestations, early detection of lymphoproliferative disease virus is essential for preventing the rapid horizontal spread of the disease that can decimate flocks. We describe development of a simple, rapid, sensitive, and highly specific assay, using the polymerase chain reaction, capable of providing differential diagnosis of the disease soon after infection.


Subject(s)
Gammaherpesvirinae/genetics , Herpesviridae Infections/veterinary , Polymerase Chain Reaction/veterinary , Poultry Diseases/diagnosis , Turkeys , Animals , Base Sequence , DNA Primers/genetics , DNA, Viral/genetics , DNA, Viral/isolation & purification , Evaluation Studies as Topic , Gammaherpesvirinae/isolation & purification , Herpesviridae Infections/diagnosis , Herpesviridae Infections/virology , Molecular Sequence Data , Polymerase Chain Reaction/methods , Polymerase Chain Reaction/statistics & numerical data , Poultry Diseases/virology , Sensitivity and Specificity
20.
Gene ; 122(2): 349-54, 1992 Dec 15.
Article in English | MEDLINE | ID: mdl-1283141

ABSTRACT

The lymphoproliferative disease virus of turkeys (LPDV) is the etiological agent of a rapidly developing lymphoproliferative process in turkeys. To better understand the genetic relationships of LPDV to other retroviruses we determined the nucleotide sequence of its pol gene. Comparative computer analyses of the deduced amino acid sequences of the reverse transcriptase and integrase domains within pol established that LPDV represents a distinct class of avian retroviruses that is most closely related to the avian leukemia-sarcoma viruses.


Subject(s)
Gene Products, pol/genetics , Retroviridae/classification , Amino Acid Sequence , Animals , Base Sequence , DNA Nucleotidyltransferases/genetics , DNA, Viral , Integrases , Molecular Sequence Data , RNA-Directed DNA Polymerase/genetics , Repetitive Sequences, Nucleic Acid , Retroviridae/genetics , Sequence Homology, Amino Acid , Turkeys
SELECTION OF CITATIONS
SEARCH DETAIL
...