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

Circulating leukocytes are important in dissemination of cytomegalovirus (CMV) infection in humans. In the mouse model of murine CMV infection (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 leukocytes contain viral DNA. In our laboratory, MCMV DNA was detected by in situ hybridization predominantly in the mononuclear cells on day 6 after acute infection. Infectious virus was recovered from day 6 mononuclear fractions in 16 of 16 mice compared with that from day 6 polymorphonuclear 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 polymorphonuclear fractions immediately following viral augmentation in the liver and spleen. MCMV immediate-early and glycoprotein B (late) transcripts were present in pooled mononuclear fractions only on day 6 of acute infection but not in pooled polymorphonuclear fractions. Collectively, these data demonstrate that (i) circulating leukocytes, predominantly mononuclear, are involved in dissemination of MCMV; (ii) a primary viremia with dissemination of MCMV to reticuloendothelial organs (liver and spleen) occurs and is followed by viral amplification and a subsequent, more intense secondary viremia; and (iii) immediate-early viral mRNA and glycoprotein B mRNA transcripts are detectable only during peak infection on day 6 in mononuclear leukocytes but not in polymorphonuclear leukocytes.