Deletion of DNA sequence in a nononcogenic variant of Herpesvirus saimiri

Koomey, Michael; Mulder, Carel; Burghoff, Robert L.; Fleckenstein, B; Desrosiers, Ronald C.

doi:10.1128/jvi.50.2.662-665.1984

Cited by 69 publications

(37 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Likewise, the complement cascade (complement control protein homolog and viral CD59 [2-4, 25, 56]) and the cytokine network (interleukin-8 receptor and interleukin-17 [1,57,64] The viral gene complex stpC/tip is regulated like a T-cell activation gene. Structural and mutational studies defined a genomic region at the terminus of the viral L-DNA as transformation relevant (8,16,17,19,39,44,52). Now, we find this region of strain C488 expressed in persistently transformed nonpermissive human T cells: two viral open reading frames, stpC and tip, are predominantly transcribed into a bicistronic inducible mRNA ( Fig.…”

Section: Virus Gene Expression In the Lytic Cycle And In Transformed mentioning

confidence: 78%

“…The genome of herpesvirus saimiri prototype strain A11 was sequenced entirely (3). The transforming functions of this virus strain were mapped to a variable, terminal region of the viral L-DNA (16,17,19,39,52). Herpesvirus saimiri C488 (18) harbors two open reading frames at the corresponding position (8) and belongs to the highly oncogenic virus group C (46,47).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Regulation of the herpesvirus saimiri oncogene stpC, similar to that of T-cell activation genes, in growth-transformed human T lymphocytes

Fickenscher

Biesinger

Knappe

et al. 1996

J Virol

Self Cite

View full text Add to dashboard Cite

Herpesvirus saimiri strain C488, a T-cell tumor virus of New World primates, transforms human T lymphocytes to stable interleukin-2-dependent growth without need for further stimulation by antigen or mitogen. The transformed cell lines show the phenotype of activated mature T cells and retain many essential features of the primary parental cells, e.g., antigen specificity. In contrast to transformed New World monkey T cells, the human lines do not support lytic growth of the virus, even after chemical stimulation. Here we show that many viral genes remain silent during episomal persistence. However, the viral oncogene stpC is predominantly transcribed and translated to a stable cytoplasmic protein of 20 kDa that is heterogeneously expressed in individual cells. This 1.7-kb mRNA is bicistronic, encoding also Tip, a viral protein interacting with the T-cell-specific tyrosine kinase Lck. stpC/tip transcripts are heavily induced upon stimulation by mitogen or phorbol ester. Block of protein synthesis does not abolish transcription: treatment with cycloheximide greatly induces stpC/tip mRNA levels. Thus, this gene complex is regulated similarly to early T-cell activation genes. Constitutive and induced expression engage different transcription start sites. The T-cell regulation of the viral genes stpC and tip may contribute to the T-cell tropism of growth transformation by herpesvirus saimiri.

show abstract

Section: Virus Gene Expression In the Lytic Cycle And In Transformed mentioning

confidence: 78%

mentioning

confidence: 99%

Regulation of the herpesvirus saimiri oncogene stpC, similar to that of T-cell activation genes, in growth-transformed human T lymphocytes

Fickenscher

Biesinger

Knappe

et al. 1996

J Virol

Self Cite

View full text Add to dashboard Cite

show abstract

“…HVS, a gamma-2 herpesvirus (rhadinovirus [34]), is related to Kaposi's sarcoma-associated herpesvirus (also called human herpesvirus 8), which is the only known human representative of the gamma-2 herpesvirus subgroup (7). While Kaposi's sarcoma-associated herpesvirus and HVS both contain homologs of known cellular genes that may influence their oncogenicity (1,35), only novel open reading frames at the left end of the HVS genome have been definitively implicated in disease induction (8,9,11,21,23,32). Sequence divergence at the left end of the viral genome defines three viral subgroups (A, B, and C) of HVS that differ with respect to oncogenic potential (8,10,27).…”

mentioning

confidence: 99%

Mutation of the Lck-Binding Motif of Tip Enhances Lymphoid Cell Activation by Herpesvirus Saimiri

Duboise

Lee

Guo

et al. 1998

J Virol

View full text Add to dashboard Cite

The proline-rich SH3-binding (SH3B) motif of the tyrosine kinase-interacting protein (Tip) of herpesvirus saimiri (HVS) is required for binding to the cellular Src family kinase Lck. We constructed a mutant form of HVS in which prolines in the SH3B motif of Tip were altered to alanines. This mutant form of Tip was incapable of binding to Lck. The mutant virus, HVS/Tip mSH3B, retained its ability to immortalize common marmoset lymphocytes in culture. In fact, common marmoset lymphocytes immortalized by the HVS/Tip mSH3B mutant displayed increased expression of HLA-DR lymphocyte activation marker, an altered pattern of tyrosine phosphorylation, increased expression of the tyrosine kinase Lyn, and a shift in electrophoretic mobility of Lck compared to cells immortalized by wild-type HVS. Experimental infection of common marmosets resulted in fulminant lymphoma with both HVS/Tip mSH3B and wild-type HVS. However, HVS/Tip mSH3B produced greater infiltration of affected organs by proliferating lymphoid cells compared to wild-type HVS. These results demonstrate that Tip binding to Lck is not necessary for transformation and that abrogation of Tip binding to Lck alters the characteristics of transformed cells and the severity of the pathologic lesions.

show abstract

“…Derivation of the molecular clones pT7.4, pTP8, pHpl .4, pHp3. 1 and pHp2.5 from the left end of L-DNA have been described previously Koomey et al, 1984). pT7.4 is a molecular clone of a 7.4-kbp TaqI fragment derived from herpes virus saimiri sequences from 0.0 to 6.7 map units.…”

Section: Resultsmentioning

confidence: 99%

“…pT7.4 is a molecular clone of a 7.4-kbp TaqI fragment derived from herpes virus saimiri sequences from 0.0 to 6.7 map units. Construction of the S4 and KH deletion mutants and their transforming and oncogenic potentials have also been published (Desrosiers et al, , 1985(Desrosiers et al, , 1986; description of the spontaneous deletion in 1latt has also been described previously (Koomey et al, 1984). Mapping of the 2.3and 4.9-kb transcripts in lytically infected OMK cells was accomplished by SI nuclease and exonuclease VII mapping procedures .…”

Section: Resultsmentioning

confidence: 99%

Viral-encoded small RNAs in herpes virus saimiri induced tumors.

Murthy¹,

Kamine²,

Desrosiers³

1986

The EMBO Journal

View full text Add to dashboard Cite

DNA sequences from the left terminus of herpes virus saimiri L‐DNA are essential for the oncogenic and transforming potential of the virus, but these sequences are not required for replication. RNA derived from 0.0 to 6.7 map units (7.4 kbp) on the herpes virus saimiri genome was studied by Northern blot hybridization and by nuclease protection analyses. Although several poly(A)‐containing RNAs were detected from this region in permissively‐infected monolayer cells in vitro, these RNAs could not be detected in cells taken directly from viral‐induced lymphomas nor in the lymphoblastoid tumor cell line 1670. Instead, these transformed T‐cells expressed four small RNAs of approximately 73, 105, 110 and 135 nt derived from this region. These small RNAs were not detected at all during the course of lytic infection of monolayer cells. Thus, synthesis of these RNAs is stringently regulated in a cell‐type specific manner. Genomic coding sequences for each of these small RNAs were mapped to 0.5‐1.2 kbp DNA fragments stretched over 4.3 kbp of viral genetic information. These findings together with the biological properties of mutants with deletions in this region have led us to speculate that one or more of these small RNAs play an essential role in cell growth transformation by herpes virus saimiri.

show abstract

Deletion of DNA sequence in a nononcogenic variant of Herpesvirus saimiri

Cited by 69 publications

References 18 publications

Regulation of the herpesvirus saimiri oncogene stpC, similar to that of T-cell activation genes, in growth-transformed human T lymphocytes

Regulation of the herpesvirus saimiri oncogene stpC, similar to that of T-cell activation genes, in growth-transformed human T lymphocytes

Mutation of the Lck-Binding Motif of Tip Enhances Lymphoid Cell Activation by Herpesvirus Saimiri

Viral-encoded small RNAs in herpes virus saimiri induced tumors.

Contact Info

Product

Resources

About