INDUCTION OF ENDOGENOUS HUMAN CYTOMEGALOVIRUS GENE-EXPRESSION AFTER DIFFERENTIATION OF MONOCYTES FROM HEALTHY CARRIERS

Monocytes are one site of carriage of the human cytomegalovirus (HCMV) genome in healthy human carriers. However, as there are conflicting d ata detailing the level of HCMV gene expression during persistence in these cells,,ve have analyzed monocytes for evidence of viral immediat e-early, early, and late transcription by using reverse transcription followed by PCR. We were unable to find evidence of HCMV lytic gene tr anscription in freshly isolated peripheral blood monocytes from HCMV-s eropositive subjects. However, as differentiation of monocytes to mono cyte-derived macrophages results in increased permissiveness to infect ion with HCMV in vitro, we examined whether such differentiation could result in reactivation of endogenous viral gene expression. Here we s how that in vitro differentiation of monocytes does result in expressi on of endogenous HCMV immediate-early genes. Although this differentia tion led to reactivation of endogenous viral immediate-early expressio n, we were unable to detect any early or late viral transcription. Coc ultivation experiments correlated with this level of gene induction, a s no productive infection was detected. These data strongly suggest a mechanism of persistence of HCMV in the peripheral blood that is indep endent of HCMV lytic gene expression and that initial phases of lytic gene expression in monocytes can be induced by differentiation of thes e cells to monocyte-derived macrophages.