Herpesvirus saimiri strain variability

Self Cite

The 110-kilobase-pair stretch of unique sequence DNA of Herpesvirus saimiri is flanked by highly repetitive DNA. Detailed restriction endonuclease mapping has localized the left junction of repetitive and unique DNA to a 100-base-pair region. H. saimiri llatt, a replication competent nononcogenic variant of strain 11, has a deletion of 2.3 kilobase pairs of sequence information that spans this left junction of repetitive and unique DNA.

supporting

confidence: 77%

Deletion of DNA sequence in a nononcogenic variant of Herpesvirus saimiri

Koomey¹,

Mulder²,

Burghoff³

et al. 1984

Self Cite

“…Herpesvirus saimiri (HVS) infection is endemic and nonpathogenic in its natural host, squirrel monkeys (Saimiri sciureus) (10,14). The same virus induces rapidly fatal T-cell lymphomas, leukemias, and lymphosarcomas in several other species of New World primates (15,18).…”

mentioning

confidence: 99%

“…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). Strains from subgroups A and C are highly oncogenic and are able to immortalize peripheral blood lymphocytes of common marmosets in vitro to interleukin 2 (IL-2)-independent growth.…”

mentioning

confidence: 99%

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

Duboise

Lee

Guo

et al. 1998

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.

“…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). The protein encoded by one of these reading frames transformed rodent fibroblasts to invasive growth in nude mice and caused epithelial tumors in transgenic animals when expressed under heterologous transcriptional control (37,51).…”

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

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.