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A role for herpesvirus saimiri orf14 in transformation and persistent infection
1Department of Microbiology and Molecular Genetics, New England Regional Primate Research Center, Harvard Medical School, Southborough, Massachusetts 01772-9102, USA.
Abstract:
The product of open reading frame 14 (orf14) of herpesvirus saimiri (HVS) exhibits significant homology with mouse mammary tumor virus superantigen. orf14 encodes a 50-kDa secreted glycoprotein, as shown previously (Z. Yao, E. Maraskovsky, M. K. Spriggs, J. I. Cohen, R. J. Armitage, and M. R. Alderson, J. Immunol. 156:3260-3266, 1996). orf14 expressed from recombinant baculovirus powerfully induces proliferation of CD4-positive cells originating from several different species. To study the role of orf14 in transformation, a mutant form of HVS (HVS Deltaorf14) was constructed with a deletion in the orf14 gene. The transforming potential of HVS Deltaorf14 was tested in cell culture and in common marmosets. Parental HVS subgroup C strain 488 immortalized common marmoset T lymphocytes in vitro to interleukin-2-independent growth, while the HVS Deltaorf14 mutant did not produce such a growth transformation. In addition, HVS Deltaorf14 was nononcogenic in common marmosets. In contrast to other nononcogenic HVS mutant viruses which were repeatedly isolated from peripheral blood mononuclear cells of infected marmosets for more than 5 months, HVS Deltaorf14 did not persist at a high level in vivo. These results demonstrate that orf14 of HVS is not required for replication but is required for transformation and for high-level persistence in vivo.
Insights
The herpesvirus saimiri (HVS) open reading frame 14 (orf14) protein is essential for T-cell transformation and oncogenesis. Deleting orf14 prevents HVS from immortalizing lymphocytes and causing tumors in marmosets.
Area of Science:
- Virology
- Immunology
- Oncology
Background:
- Herpesvirus saimiri (HVS) is a T-lymphotropic virus known to cause tumors in nonhuman primates.
- The function of open reading frame 14 (orf14) in HVS pathogenesis is not fully understood.
- orf14 encodes a secreted glycoprotein with homology to mouse mammary tumor virus superantigen.
Purpose of the Study:
- To investigate the role of orf14 in the transforming potential and oncogenicity of HVS.
- To determine if orf14 is necessary for HVS-induced T-lymphocyte immortalization and tumor formation.
Main Methods:
- Construction of a deletion mutant HVS (HVS Deltaorf14) lacking the orf14 gene.
- Testing the in vitro transforming potential of HVS Deltaorf14 on common marmoset T lymphocytes.
- Evaluating the in vivo oncogenicity and persistence of HVS Deltaorf14 in common marmosets.
Main Results:
- Parental HVS strain 488 immortalized T lymphocytes in vitro, while HVS Deltaorf14 did not.
- HVS Deltaorf14 was nononcogenic in common marmosets.
- HVS Deltaorf14 showed reduced persistence in vivo compared to other nononcogenic HVS mutants.
Conclusions:
- orf14 is essential for HVS-mediated T-lymphocyte transformation and interleukin-2-independent growth.
- orf14 plays a critical role in the oncogenicity of HVS.
- orf14 is required for high-level persistence of HVS in vivo, though not for viral replication.