FIG 7 .

Working model for TMER4 ncRNA’s essential role at a key MLN bottleneck to facilitate hematogenous dissemination of MHV68. The TMER4 double stem-loop mutant displays normal acute replication in the lungs (A), normal trafficking to and acute replication in the MLN (B), and normal leukocyte distribution and latency establishment in the MLN (C). However, the TMER4 mutant is highly attenuated for infection of circulating leukocytes (D) and highly attenuated for latent infection at peripheral sites (E). Therefore, we propose that the TMER4 ncRNA mediates an essential function at a critical viral dissemination bottleneck in the MLN. Because B cells are required for MHV68 trafficking to peripheral sites, the key dissemination bottleneck is likely related to (i) intrinsic or (ii) extrinsic stimulation of B cell egress from MLN or (iii) promotion of survival of infected MLN B cells.