Restricted replication of herpes simplex virus in human monocyte cultures: role of interferon

Exposure of fresh human monocytes in culture to high or moderate concentrations of herpes simplex virus (HSV) resulted in an abortive infection or in a highly restricted replication of the virus. Infectious progeny virus yields were obtained either by diluting the inoculum virus to multiplicities of 0.1-0.0001 PFU/cell, or by cultivation of the cells for a few days before exposure to the virus. Interferon was synthesized and released into the medium of monocyte cultures infected with the higher multiplicities, while the lower productive multiplicities or inoculations of HSV into mature macrophage cultures resulted in a production of only small amounts, if any, of interferon. Inhibition of the morphological differentiation of monocytes was seen in cultures infected with the higher multiplicities of HSV (m.o.i. 1.0-0.1 PFU/cell) and was not unlike that caused by exogenous interferon added into uninfected monocyte cultures. Antisera against the leukocyte interferon were able to enhance the production of infectious HSV in monocyte-macrophage cultures. These results suggest that interferon induced in monocytes by high multiplicities of HSV can prevent the productive replication of HSV. Apart from its possible direct antiviral effect interferon may cause this restriction of HSV replication by inhibiting the differentiation of host monocytes.