 |
Herpes Virus Trashes Detection Mechanism to Hide from Immune System
St. Louis, Jan. 14, 2003 — Herpes viruses are
notorious for their ability to hide from the immune system and establish
lifelong infections. Researchers at Washington University School of
Medicine in St. Louis have discovered how one mouse herpes virus escapes
detection. The study appears in the January issue of the journal
Immunity.
"These findings not only provide a better
understanding of viral infections," says study leader Ted H. Hansen,
Ph.D., professor of genetics, "they also offer novel insights into basic
cellular processes in the immune system."
Like police cars cruising a neighborhood,
immune cells known as cytotoxic T cells patrol the body looking for signs
of trouble, such as virus-infected cells.
Cells communicate with the immune system by
displaying protein fragments on their surface, including viral proteins.
When cytotoxic T cells find viral proteins on a cell's surface, they
destroy the cell and thereby eliminate the virus.
Molecules known as major histocompatibility
complex class 1 (MHC class 1) are responsible for displaying the protein
fragments, known as peptides, on the cell surface. Cells make fleets of
MHC class 1 molecules, each of which is assembled from two separate pieces
plus the peptide. After each MHC class 1 molecule is completed, it travels
to the cell surface to display its peptide to passing immune cells.
"MHC class I is the body's most important
mechanism for fighting off most viral infections," says lead author Lonnie
P. Lybarger, Ph.D., postdoctoral fellow in genetics. "Not surprisingly,
herpes viruses have evolved ways to block that immune response."
Hansen, Lybarger and their colleagues used a
mouse virus known as gamma2-herpesvirus to discover exactly how the virus
does this. The virus is closely related to the human herpes virus
associated with Kaposi's sarcoma, a cancer of blood vessels that occurs in
some people with AIDS.
Research has shown that cells assemble MHC
class 1 molecules with the help of other molecules known as chaperones. In
this study, the investigators found that in cells infected with
gamma2-herpesvirus, a viral protein known as mK3 joins the chaperones as
they prepare to assemble an MHC class 1 molecule.
Then, as assembly occurs, the mK3 protein
makes a subtle change in the MHC class 1 molecule that marks it as waste.
So instead of traveling to the cell surface as it should, the MHC class 1
molecule is shunted off to the side and destroyed.
"The finding that mK3 requires chaperone
molecules to function and hides out with them came as a surprise," says
Lybarger. "It represents a new strategy for blocking immune detection, and
it suggests that there are probably other viral proteins that use host
molecules to target MHC class 1."
The researchers are using gamma2-herpesvirus
and the herpes virus associated with Kaposi's sarcoma to identify some of
those additional protein-protein interactions between virus and host.
Hansen attributes the success of this project
to an effective collaboration between his laboratory, which specializes in
the presentation of MHC class 1 molecules, and the virology laboratory of
Herbert W. Virgin IV, M.D., Ph.D., professor of pathology and immunology
and of molecular microbiology.
###
Lybarger L, Wang X, Harris MR, Virgin HW, Hansen TH. Virus subversion of
the MHC class 1 peptide-loading complex.
Immunity,
January 2003.
Funding from the National Institute of Allergy and Infectious Diseases
supported this research.
|