Herpes Simplex Virus Infection in Human Monocyte Cultures: Dose-dependent Inhibition of Monocyte Differentiation Resulting in Abortive Infection

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Abstract
Monocyte-enriched cultures of human blood leukocytes were exposed to herpes simplex virus (HSV) at multiplicities of infection (m.o.i.) ranging from about 0.0001-10 PFU (plaque forming units)/cell. Highest maximum progeny virus titers were invariably obtained with low initial m.o.i. of 0.01-0.0001 PFU/cell, while little if any infectious progeny was produced in cultures inoculated with the highest virus concentrations. By the time of maximum virus production, i.e., at 5-7 days after inoculation, monocytes in the uninfected cultures had mostly differentiated to macrophages. This differentiation was partially inhibited in cultures initially exposed to the higher concentrations of HSV. Synthesis of HSV antigens was detected by indirect immunofluorescence both in the high m.o.i. cultures and in the productively infected cultures. By this criterion, a maximum of 10-15% of all adherent cells became infected in both culture types. Higher doses of HSV may prevent the subsequent completion of the HSV infectious cycle by inhibiting cellular maturation.