Deregulation of cell growth by the K1 gene of Kaposi's sarcoma-associated herpesvirus.
At a position equivalent to the gene encoding the saimiri transforming protein (STP) of herpesvirus saimiri (HVS), Kaposi's sarcoma-associated herpesvirus (KSHV) contains a distinct open reading frame called K1. Although KSHV and HVS are related members of the rhadinovirus subgroup of gamma herpesviruses, K1 and STP exhibit no similarity in amino acid sequence or in structural organization. Since STP is required for the oncogenic potential of HVS, we investigated the functional consequence of K1 expression. Expression of the K1 gene in rodent fibroblasts produced morphologic changes and focus formation indicative of transformation. A recombinant herpesvirus in which the STP oncogene of HVS was replaced with K1, immortalized primary T lymphocytes to IL-2 independent growth and induced lymphoma in common marmosets. These results demonstrate the transforming potential of the K1 gene of KSHV.
Lee
H
H
New England Regional Primate Research Center, Harvard Medical School, Southborough, MA 01772-9102, USA.
Veazey
R
R
Williams
K
K
Li
M
M
Guo
J
J
Neipel
F
F
Fleckenstein
B
B
Lackner
A
A
Desrosiers
R C
RC
Jung
J U
JU
D000163:Acquired Immunodeficiency Syndrome / Q000150:complications; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D017931:DNA Primers; D004279:DNA, Viral / Q000235:genetics; D005814:Genes, Viral; D006567:Herpesvirus 2, Saimiriine / Q000235:genetics / Q000472:pathogenicity; D019288:Herpesvirus 8, Human / Q000235:genetics*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009856:Oncogene Proteins, Viral / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics; D016366:Open Reading Frames; D016133:Polymerase Chain Reaction; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000737:chemistry; D012514:Sarcoma, Kaposi / Q000209:etiology / Q000473:pathology / Q000821:virology*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014162:Transfection; D014764:Viral Proteins / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics*
D017931:DNA Primers; D004279:DNA, Viral; C111600:K1 protein, Human herpesvirus 8; D009856:Oncogene Proteins, Viral; D011993:Recombinant Fusion Proteins; C064364:STP protein, Herpesvirus saimiri; D014764:Viral Proteins