The gene region UL128-UL131A of human cytomegalovirus (HCMV) is essential for monocyte infection and block of migration - Characterisation of the infection of primary human monocytes
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Monocytes are targets of HCMV infection and vehicles for viral dissemination in vivo. By using two TB40E-derived BAC clones expressing the full-length (BAC4) or a truncated form of pUL128 (BAC1), the role of UL128 for infection and motility of monocytes has been investigated. Like TB40E, BAC4 was able to infect and to express IE gene products in monocytes. BAC4-infected monocytes exhibited normal cytoskeleton architecture but a complete inability to migrate in response to chemokines as a consequence of intracellular retention of the cognate chemokine receptors. Similar to TB40F, BAC1 virions entered into monocytes but were retained in cytoplasmatic vesicles and IE gene expression could not be detected. Moreover, the chemokine responsiveness of monocytes inoculated with BAC1 was normal. In order to exclude that second-site mutations were responsible for the observed phenotype, revertant viruses were tested. The re-introduction of the wild-type UL128 sequence in BAC1 resulted in BAC1repaired (BAC1rep) and the introduction of the mutation responsible for the truncation in BAC4 resulted in BAC4mutated (BAC4mut). It has been observed that only BAC4 and BAC1rep, expressing the full-length form of pUL128, were able to infect monocytes and block their migration. Finally, monocytes incubated with the recombinant UL128 protein (rpUL128) showed the same block of migration like BAC4 and BAC1rep infected cells, while monocytes treated with an irrelevant recombinant protein migrated normally. Further more it has been observed that rpUL128 induced monocyte recruitment with the same potency as MCP-1, supporting the hypothesis that pUL128 can act as a chemokine and thus lead to chemokine receptor binding and internalisation.
Subject HeadingsCytomegalie-Virus [GND]
Cytomegalovirus receptor [MeSH]