Infection of primary human monocytes by Epstein-Barr virus

Previous studies have reported that infection of monocytes by viruses such as cytomegalovirus and human immunodeficiency virus weakens host natural im munity, In the present study, we demonstrated the capability of Epstein-Bar r virus (EBV) to infect and replicate in freshly isolated human monocytes, Using electron microscopy analysis, we observed the presence of EBV virions in the cytoplasm and nuclei of approximately 20% of monocytes. This was co nfirmed by Southern blot analysis of EBV genomic DNA sequences in isolated nuclei from monocytes, Infection of monocytes by EBV leads to the activatio n of the replicative cycle. This was supported by the detection of immediat e-early lytic mRNA BZLF-1 transcripts, and by the presence of two early lyt ic transcripts (BALF-2, which appears to function in DNA replication, and B HRF-1, also associated with the replicative cycle), The late lytic BcLF-1 t ranscripts, which code for the major nucleocapsid protein, were also detect ed, as well as EBNA-1 transcripts. However, attempts to detect EBNA-2 trans cripts have yielded negative results. Viral replication was also confirmed by the release of newly synthesized infectious viral particles in supernata nts of EBV-infected monocytes. EBV-infected monocytes were found to have si gnificantly reduced phagocytic activity, as evaluated by the quantification of ingested carboxylated fluoresceinated latex beads. Taken together, our results suggest that EBV infection of monocytes and alteration of their bio logical functions might represent a new mechanism to disrupt the immune res ponse and promote viral propagation during the early stages of infection.