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.

In vivo attenuation of recombinant murine gammaherpesvirus 68 (MHV-68) is due to the expression and immunogenicity but not to the insertion of foreign sequences.

Recombinant herpesviruses are increasingly utilized to study herpesvirus biology. For recombinant viruses carrying insertions of foreign sequences, attenuated phenotypes in vivo have been frequently observed. In most cases, the underlying mechanisms were not clear or have not been investigated.

Protective vaccination with hepatitis C virus NS3 but not core antigen in a novel mouse challenge model.

Background: Efficient vaccines against hepatitis C virus (HCV) infection are urgently needed. Vaccine development has been hampered by the lack of suitable small animal models to reliably test the protective capacity of immmunization.

Methods: We used recombinant murine gammaherpesvirus 68 (MHV-68) as a novel challenge virus in mice and tested the efficacy of heterologous candidate human vaccines based on modified vaccinia virus Ankara or adenovirus, both delivering HCV non-structural NS3 or core proteins.

A gammaherpesviral internal repeat contributes to latency amplification.

Background: Gammaherpesviruses cause important infections of humans, in particular in immunocompromised patients. The genomes of gammaherpesviruses contain variable numbers of internal repeats whose precise role for in vivo pathogenesis is not well understood.

Methodology/principal Findings: We used infection of laboratory mice with murine gammaherpesvirus 68 (MHV-68) to explore the biological role of the 40 bp internal repeat of MHV-68.

Recombinant murine gammaherpesvirus 68 (MHV-68) as challenge virus to test efficacy of vaccination against chronic virus infections in the mouse model.

Efficient vaccines against AIDS, Hepatitis C and other persistent virus infections are urgently needed. Vaccine development has been especially hampered by the lack of suitable small animal models to reliably test the protective capacity of candidate vaccines against such chronic viral infections. A natural mouse pathogen such as MHV-68 that persists lifelong after infection, appears to be a particularly promising candidate for a more relevant model system.

The 37-kDa/67-kDa laminin receptor acts as a receptor for infectious prions and is inhibited by polysulfated glycanes.

Background: Recently, we showed that the 37-kDa/67-kDa laminin receptor (LRP/LR) acts as the receptor of the cellular prion protein.

Methods: For the present study, we investigated the binding of the murine scrapie prion protein (moPrP27-30) to baby hamster kidney (BHK) cells, using the Semliki Forest virus system.

Results: The enhanced binding of moPrP27-30 to BHK cells expressing moLRP::FLAG was inhibited by the LRP/LR-specific antibody W3, which suggests that LRP/LR acts as a receptor for the scrapie form of the prion protein, PrP(Sc).