Resistance of human blood monocytes to infection with herpes simplex virus

Human blood monocytes isolated by centrifugal elutriation were resistant to infection with herpes simplex virus type 1 (HSV). In vitro cultivation for several days resulted in a stepwise increase of virus yield. Similar amounts of virus absorbed to fresh and cultured monocytes. No viral DNA was associated with the nuclear fraction of freshly isolated monocytes early after infection indicating that early steps of virus infection were already inhibited in resistant cells. This argues against HSV induced interferon (IFN) being a major mediator of resistance. Culturing the cells for some hours was sufficient to overcome the early block. However, as revealed by virus yield assays, monocytes after 1 day of cultivation were not as susceptible as cells after 6 days of cultivation. Viral sequences could be demonstrated in the nuclei of freshly isolated monocytes after treatment with the fusion-promoting agent polyethylene glycol. Under these conditions no DNA replication occurred, indicating that overcoming the block of viral DNA entry into the nucleus was not sufficient to break resistance of the cells. Thus, the results show that several mechanisms are involved in the primary resistance of human blood monocytes to HSV.