Expression of Interleukin 2 Receptors in T Cells Transformed by Strains of &lt;i&gt;Herpesvirus saimiri&lt;/i&gt; Representing Three DNA Subgroups

Medveczky, Peter G.; Medveczky, Maria M.

doi:10.1159/000150095

Cited by 8 publications

(5 citation statements)

References 16 publications

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“…HVS strains are classified into three subgroups, A, B, and C, on the basis of their transforming potential and differences in the terminal long unique DNA sequence (49,50). Among these subgroups, only subgroups A and C have been shown to immortalize T lymphocytes of marmosets and other New World primates (21).…”

Section: Discussionmentioning

confidence: 99%

ORF73 of Herpesvirus Saimiri Strain C488 Tethers the Viral Genome to Metaphase Chromosomes and Binds to cis -Acting DNA Sequences in the Terminal Repeats

Verma

Robertson

2003

J Virol

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Kaposi's sarcoma (KS)-associated herpesvirus (KSHV), a human oncogenic gamma-2-herpesvirus, transforms human endothelial cells and establishes latent infection at a low efficiency in vitro. During latent infection, only a limited number of genes are expressed, and the circularized viral genome is maintained as a multicopy episome. Latency-associated nuclear antigen (LANA), exclusively expressed during latency, has been shown to have a multifunctional role in KS pathogenesis. LANA tethers the viral episome to the host chromosome, thus ensuring efficient persistence of the viral genome during successive rounds of cell division. Besides episome maintenance, LANA modulates the expression of genes of various cellular and viral pathways, including those of retinoblastoma protein and p53. Herpesvirus saimiri (HVS), another gamma-2-herpesvirus, primarily infects New World primates. Orf73, encoding the nuclear antigen of HVS, is the positional homolog of the LANA gene, and the ORF73 protein has some sequence homology to KSHV LANA. However, the function of ORF73 of HVS has not been thoroughly investigated. In this report, we show that HVS ORF73 may be important for episome persistence and colocalizes with the HVS genomic DNA on metaphase chromosomes. Furthermore, HVS terminal repeats (TRs) contain a cis-acting sequence similar to that in KSHV TRs, suggesting that the LANA binding sequence is conserved between these two viruses. This cis-acting element is sufficient to bind HVS ORF73 from strains C488 and A11, and plasmids containing the HVS C488 TR element are maintained and replicate in HVS C488 ORF73-expressing cells.Kaposi's sarcoma (KS)-associated herpesvirus (KSHV), also known as human herpesvirus 8, is a gammaherpesvirus found in all forms of KS (3, 52, 64;

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Section: Discussionmentioning

confidence: 99%

ORF73 of Herpesvirus Saimiri Strain C488 Tethers the Viral Genome to Metaphase Chromosomes and Binds to cis -Acting DNA Sequences in the Terminal Repeats

Verma

Robertson

2003

J Virol

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“…In monkeys and rabbits the virus transforms CD8 + lymphocytes (Kiyotaki et al, 1986) and causes malignant lymphoproliferations (Daniel et al, 1974;Melendez et al, 1969). Several data indicate that lymphokine and growth factor upregulation is involved in the process and mediate autocrine cell growth (Medveczky & Medveczky, 1989). High-level interleukin (IL)-2 receptor expression (Medveczky & Medveczky, 1989) and IL-4 secretion was detected with transformed monkey cell lines (M. Medveczky, P. Geck, C.-S. Chou, A.…”

Section: Introductionmentioning

confidence: 99%

“…Several data indicate that lymphokine and growth factor upregulation is involved in the process and mediate autocrine cell growth (Medveczky & Medveczky, 1989). High-level interleukin (IL)-2 receptor expression (Medveczky & Medveczky, 1989) and IL-4 secretion was detected with transformed monkey cell lines (M. Medveczky, P. Geck, C.-S. Chou, A. Brown, J. Cus & P.G.…”

Section: Introductionmentioning

confidence: 99%

Herpesvirus saimiri small RNA and interleukin-4 mRNA AUUUA repeats compete for sequence-specific factors including a novel 70K protein

Geck

Medveczky

Chou

et al. 1994

Journal of General Virology

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A highly oncogenic strain of the lymphotropic tumour virus herpesvirus saimiri (HVS; strain 484-77) expresses four small RNAs (HSUR1 to 4) in high copy numbers in transformed T cells. In HSUR1 and HSUR2 the 5' terminal regions contain conserved AUUUA sequence repeats. The same AUUUA repeats occur in the 3' noncoding regions of growth factor, lymphokine and protooncogene mRNAs, and the sequence is involved in rapid mRNA degradation. We report here that by using a highly specific u.v. cross-linking method we identified a novel 70K binding factor with AUUUA sequence specificity. Non-radiolabelled competition and V8 protease analysis show that the protein can form a complex with the 3' non-coding region of interleukin-4 mRNA and bind the AUUUA repeats of a HVS small RNA. We also detected an AUUUA-specific minor 32K human protein with the same electrophoretic mobility as a marmoset factor implicated in growth factor mRNA destabilization. The findings are consistent with the hypothesis that the viral small RNAs can compete for factors involved in rapid degradation of growth factor mRNAs and may contribute to viral oncogenesis.

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“…Both viruses can induce a similar pathology after infection of rabbits. The lymphocytes involved are of an analogous phenotype, and lymphocytic cell lines can be established from naturally and experimentally infected animals (26,36,45,72).…”

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confidence: 99%

Primary structure of the alcelaphine herpesvirus 1 genome

Ensser¹,

Pflanz²,

Fleckenstein³

1997

J Virol

142

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Alcelaphine herpesvirus 1 (AHV-1) causes wildebeest-associated malignant catarrhal fever, a lymphoproliferative syndrome in ungulate species other than the natural host. Based on biological properties and limited structural data, it has been classified as a member of the genus Rhadinovirus of the subfamily Gammaherpesvirinae. Here, we report on cloning and structural analysis of the complete genome of AHV-1 C500. The low GC content DNA (L-DNA) region of the genome consists of 130,608 bp with low (46.17%) GC content and marked suppression of CpG dinucleotide frequency. Like in herpesvirus saimiri, the prototype of the rhadinoviruses, the L-DNA is flanked by approximately 20 to 25 GC-rich (71.83%) high GC content DNA (H-DNA) repeats of 1,113 to 1,118 nucleotides. The analysis of the L-DNA sequence revealed 70 open reading frames (ORFs), 61 of which showed homology to other herpesviruses. The conserved ORFs are arranged in four blocks collinear to other Rhadinovirus genomes. These gene blocks are flanked by nonconserved regions containing ORFs without similarities to known herpesvirus genes. Notably, a spliced reading frame with a coding capacity for a 199-amino-acid protein is located in a position homologous to the transforming genes of herpesvirus saimiri at the left end of the L-DNA. A gene with homology to the semaphorin family is located adjacent to this. Despite common biological and epidemiological properties, AHV-1 differs significantly from herpesvirus saimiri with regard to cell homologous genes, probably using a different set of effector proteins to achieve a similar T-lymphocyte-transforming phenotype. MATERIALS AND METHODS Cell lines and viral culture. The bovine epithelial kidney cell line MDBK (ATCC CCL 22) was propagated in Dulbecco's modified Eagle's medium supplemented with 10% fetal bovine serum, 100 g of gentamicin per ml, and 350 g of L-glutamine per ml. AHV-1 strains C500 (62) and WC11 (63) were serially propagated by infection of fresh MDBK cells with aliquots of infected MDBK cells showing cytopathic changes in more than 80% of the cells. AHV-1 C500 was obtained from H. W. Reid (Moredun Research Institute, Edinburgh, United Kingdom), and the attenuated WC11 strain was obtained from D. W. Verwoerd (Veterinary Research Institute, Onderstepoort, South Africa). For the preparation of virions, tissue culture supernatant was precleared by centrifugation at 2,000 ϫ g. Strain C500 virions (passage 5) were pelleted by centrifugation at 50,000 ϫ g with an SW28 rotor. The viral DNA was extracted from the pellet with phenol-chloroform and precipitated with ethanol. WC11 DNA was further purified by density gradient centrifugation as described previously (37). Cloning procedures.

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Expression of Interleukin 2 Receptors in T Cells Transformed by Strains of <i>Herpesvirus saimiri</i> Representing Three DNA Subgroups

Cited by 8 publications

References 16 publications

ORF73 of Herpesvirus Saimiri Strain C488 Tethers the Viral Genome to Metaphase Chromosomes and Binds to cis -Acting DNA Sequences in the Terminal Repeats

ORF73 of Herpesvirus Saimiri Strain C488 Tethers the Viral Genome to Metaphase Chromosomes and Binds to cis -Acting DNA Sequences in the Terminal Repeats

Herpesvirus saimiri small RNA and interleukin-4 mRNA AUUUA repeats compete for sequence-specific factors including a novel 70K protein

Primary structure of the alcelaphine herpesvirus 1 genome

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