Fatigue, a common symptom of many acute and chronic medical conditions, reduces both quality of life and workplace productivity and can be disabling. Open reading frame 45 (ORF45) is conserved among the members of the Gammaherpesvirinae subfamily and has been suggested to be a virion tegument protein. This stems in part, from the high level of seropositivity for EBV (> 95%) and the exquisite species specificity of EBV. Specifically, M3 was essential for two features unique to the wood mouse: virus-dependent inducible bronchus-associated lymphoid tissue (iBALT) in the lung and highly organized secondary follicles in the spleen, both predominant sites of latency in these organs. However, limiting-dilution assays to measure viral reactivation demonstrated that the mature DCs were latently infected with gamma HV-68. In order to test whether virus-induced antibodies reduce virion infectivity by binding to gB, monoclonal antibodies (mAbs) were derived from MHV-68-infected mice. This allowed us to identify a genital excretion site of MHV-68 following intranasal infection and latency establishment in female mice.
The ORF48-null mutation remarkably reduced the viral replication efficiency in cell culture. Thus, these data demonstrate that TLR stimulation can drive MHV68 reactivation from latency and suggests that periodic pathogen exposure may contribute to the homeostatic maintenance of chronic gammaherpesvirus infection through stimulating virus reactivation and reseeding latency reservoirs.