Appeal No. 2001-0759
Application 08/809,186
secretion. Accordingly, vpr inhibits cytokine production/secretion by these cells due to
immunoglobulin activation. Id. It has been further discovered that vpr acts like steroids
in steroid sensitive cells. In addition, vpr is active in steroid non-sensitive cells, i.e., vpr
has steroid like activity but is active in a broader spectrum of cells. Specification,
pages 10-11.
In particular, the present invention relates to methods of modifying macrophage
state of differentiation by contacting macrophage cells with vpr protein. It has been
discovered that vpr induces changes in macrophage cells. Specification, page 19.
The vpr gene has been shown to increase the kinetics of viral replication and
cytopathicity in T-lymphocytes. Specification, page 20. The specification also
indicates that an rip-1/vpr complex associates with the activated glucocorticoid receptor
(GR) type II receptor complex as part of the signaling pathway for vpr. The rip-
1/vpr/GR type II receptor complex translocates into the nucleus in the absence of
steroid compounds normally associated with GR-type II receptor translocation.
Specification, page 21. It has been discovered that rip-1 is associated with the GR
type II receptor complex and that rip-1 co-translocates into the nucleus together with
GR-type II receptor when GR-type II receptors are induced to translocate as the result
of binding to steroid hormones. As such, according to the specification, these
discoveries provide a new target for the modulation of GR-type II complex translocation.
The vpr compound and fragments thereof which induce GR -type II complex
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