BIPHASIC VIREMIA AND VIRAL GENE-EXPRESSION IN LEUKOCYTES DURING ACUTECYTOMEGALOVIRUS-INFECTION OF MICE

Circulating leukocytes are important in dissemination of cytomegalovir us (CMV) infection in humans. In the mouse model of murine CMV infecti on (MCMV), it has been shown that infection peaks on days 5 to 7 after experimental infection, when 0.01 to 0.1% of the circulating leukocyt es contain viral DNA. In our laboratory, MCMV DNA was detected by in s itu hybridization predominantly in the mononuclear cells on day 6 afte r acute infection. Infectious virus was recovered from day 6 mononucle ar fractions in 16 of 16 mice compared with that from day 6 polymorpho nuclear fractions in 4 of 16 mice. An eclipse phenomenon was noted in the blood leukocytes by quantitative blot hybridization: the amount of MCMV DNA present was small on day 2, diminished on days 3 and 4, and then increased markedly on days 5 and 6 in both the mononuclear and po lymorphonuclear fractions immediately following viral augmentation in the liver and spleen. MCMV immediate-early and glycoprotein B (late) t ranscripts were present in pooled mononuclear fractions only on day 6 of acute infection but not in pooled polymorphonuclear fractions. Coll ectively, these data demonstrate that (i) circulating leukocytes, pred ominantly mononuclear, are involved in dissemination of MCMV; (ii) a p rimary viremia with dissemination of MCMV to reticuloendothelial organ s (liver and spleen) occurs and is followed by viral amplification and a subsequent, more intense secondary viremia; and (iii) immediate-ear ly viral mRNA and glycoprotein B mRNA transcripts are detectable only during peak infection on day 6 in mononuclear leukocytes but not in po lymorphonuclear leukocytes.