Perturbation of lytic and latent gammaherpesvirus infection in the absence of the inhibitory receptor CEACAM1.

Control of gammaherpesvirus infections requires a complex, well
orchestrated immune response regulated by positive and negative
co-signaling molecules. While the impact of co-stimulatory
molecules has been addressed in various studies, the role of
co-inhibitory receptors has not been tested. The ITIM-bearing
CEACAM1 is an inhibitory receptor expressed by a variety of immune
cells, including B, T and NK cells. Using Ceacam1(-/-) mice, we
analyzed the in vivo function of CEACAM1 during acute and latent
murine gammaherpesvirus 68 (MHV-68) infection. During acute lytic
replication, we observed lower virus titers in the lungs of
Ceacam1(-/-) mice than in WT mice. In contrast, during latency
amplification, Ceacam1(-/-) mice displayed increased splenomegaly
and a higher latent viral load in the spleen. Analysis of the
immune response revealed increased virus-specific antibody levels
in Ceacam1(-/-) mice, while the magnitude of the T cell-mediated
antiviral immune response was reduced. These findings suggest that
inhibitory receptors can modulate the efficacy of immune responses
against gammaherpesvirus infections.