| The identification of EBV strain variants is an effective approach to investigate elements of infection and to reveal fundamental information about EBV biology. Several polymorphic regions exist in the EBV genome, but the most discriminating loci for EBV genotyping is the latent membrane protein 1 (LMP1) gene. In these studies a heteroduplex tracking assay (HTA) specific for LMP1 was used to differentiate between the seven distinct EBV strains and determine their relative abundance in a mixed population.; Multiple EBV strains were detected in both healthy and immunocompromised subjects. Infectious mononucleosis patients were also infected with multiple strains, revealing that multiple strains are acquired at primary infection. In several incidences, new strains were detected at later time points suggesting that the immune response may not be capable of preventing secondary infections.; EBV persists in a latent state in memory B-lymphocytes in the periphery, and infectious virions are present in the oral cavity. Strains detected in the peripheral blood lymphocytes (PBLs) and oral cavity were frequently distinct in each subject, indicating that each compartment represents a distinct infection and likely reflects the ability of EBV to infect different cell types. The cell-free blood plasma of infectious mononucleosis subjects, often contained a strain profile that was distinct from the PBLs, suggesting that another compartment exists to supply the plasma with EBV, which was a mixture of viral DNA and encapsidated virions.; In asymptomatic carriers who have relatively low viral loads, EBV was consistently detected in the oral cavity, indicating that chronic reactivation is a normal, and perhaps, essential component of the EBV life cycle. Distinct strains persisted over multiple time points in the oral cavity suggesting that epithelial cells, specifically, play an important role in infection. Furthermore, the strain profiles were dynamic and appeared to cycle between the compartments suggesting that the maintenance of persistent infection may require the reinfection of B-lymphocytes in the oral cavity that replenish the population of infected cells in the periphery. |
