Abstracts (complete list) - Wissenschaft Online

Sabrina Hoffmann, Michael Winkler, Marcus Gutscher, Helmut Fickenscher, Carsten
Watzl
Cytomegalovirus infected fibroblasts downregulate ligands
for the Natural Cytotoxicity receptors NKp30 and NKp44
Activation of Natural Killer (NK) cells is controlled by an elaborate system of activating
and inhibiting receptors. The family of Natural Cytotoxicity Receptors (NCR) plays an
important role in NK cell activation. The members of this family, including NKp30 and
NKp44, have been shown to be involved for NK cell activation during tumor clearance
and the lysis of virally infected cells. Although the cellular ligands to these receptors still
remain elusive to date, we are able to detect these ligands using novel trimeric NCR
fusion proteins.
Human Cytomegalovirus (hCMV) is known to introduce a vast number of changes within
the host cell machinery upon infection. Here we examine the role of NCR ligands during
CMV infection of primary human foreskin fibroblasts (HFF). Non-infected fibroblasts
readily express the ligands for NKp30 and NKp44 on their surface. Upon infection HFF
show a clear decrease in staining intensity for both ligands. Killing of HFF by human NKcells
is partly dependent on NKp30. Interestingly, the lysis of CMV infected HFF is no
longer dependent on NKp30. UV-inactivation of viral particles and inhibition of
expression of CMV early genes abrogates this effect suggesting that a specific CMV gene
product is responsible. These results demonstrate that CMV infection causes a downmodulation
of the ligands for NKp30 and NKp44, leading to reduced activation of NK
cells. The down-regulation of NCR ligands might therefore constitute a new strategy of
hCMV to escape the attac of NK cells.