The first major defect observed in an in vivo MHV68.DHS infection is significantly lower levels of the virus in the lymph nodes at 10 dpi. Following an intranasal infection, wild-type MHV68 undergoes lytic replication in the lung and upper respiratory track, after which the virus drains to the lymph nodes and spleen where a variety of cell types are infected, including macrophages, dendritic cells, and B-cells [37, 50, 51, 52] . A burst of lytic replication occurs at these sites [30, 32] , after which replicating virus is cleared and long-term latency is established. Lower levels of MHV68.DHS in the lymph node could be caused by a cell-type specific role for muSOX-dependent mRNA degradation in viral replication or immune evasion during viral transport to, and maintenance in, the lymphatic tissue. The observation that the EBV muSOX homolog (BGLF5) down-regulates HLA class I molecules and CD8 + T cell recognition in cultured cells may support this model [25] . The means by which the virus traffics to the sites of latency establishment remain unclear, yet it is likely that latently infected B cells carry the virus given that viremia is undetectable during an infection, and latently infected B cells are present in the lung very early after infection [37, 53, 54] . A failure of MHV68.DHS to establish latency in these cells might also cause their selective immune-based eradication and decreased accumulation in the lymph nodes. Alternatively, muSOX could influence the ability of the virus to reactivate from latency, as this process has been linked to efficient latency establishment. Mutations in a number of genes alter the frequency of lytic reactivation and lead to lower levels of latency establishment following an intranasal infection, such as vcyclin (ORF72) [55] , M1 [56] , M2 [57, 58] , and LANA (ORF73) [59, 60] , but unlike muSOX these genes are all expressed during latency as well as during lytic replication [61] . Mutations in the lytic ORF36 gene encoding a protein kinase also lead to defects in latency establishment and reactivation [62, 63] , which have been tracked to the requirement for ORF36 to inhibit the IRF-3 mediated type I interferon response [62] and its modification of the DNA-damage response protein H2AX [63] . Experiments are currently underway to examine MHV68.DHS replication, reactivation, and latency establishment in specific cell types relevant to in vivo infection.