A unique variant of lymphocytic choriomeningitis virus that induces pheromone binding protein MUP: Critical role for CTL

Significance Pheromones play essential roles in host communications and sexual attraction, and thus regulate adaptive behavior. Here we present the discovery and characterization of the first known virus, a variant of lymphocytic choriomeningitis virus, that selectively induces pheromone binding protein mouse urinary protein. Furthermore, we found that cytotoxic T lymphocytes play a critical role in mouse urinary protein generation. Lymphocytic choriomeningitis virus (LCMV) WE variant 2.2 (v2.2) generated a high level of the major mouse urinary protein: MUP. Mice infected with LCMV WE v54, which differed from v2.2 by a single amino acid in the viral glycoprotein, failed to generate MUP above baseline levels found in uninfected controls. Variant 54 bound at 2.5 logs higher affinity to the LCMV receptor α-dystroglycan (α-DG) than v2.2 and entered α-DG–expressing but not α-DG–null cells. Variant 2.2 infected both α-DG–null or –expressing cells. Variant 54 infected more dendritic cells, generated a negligible CD8 T cell response, and caused a persistent infection, while v2.2 generated cytotoxic T lymphocytes (CTLs) and cleared virus within 10 days. By 20 days postinfection and through the 80-day observation period, significantly higher amounts of MUP were found in v2.2-infected mice. Production of MUP was dependent on virus-specific CTL as deletion of such cells aborted MUP production. Furthermore, MUP production was not elevated in v2.2 persistently infected mice unless virus was cleared following transfer of virus-specific CTL.