Amazing stuff!
"scientists ... have discovered that the fate of an individual infected cell, too, depends on the number of virions that enter it. ...
the researchers reveal that the cellular infectious dose determines whether a virus will become active in the cell or enter a dormant state. These findings pave the way for therapies that could control the outcome of infection. ...
While most viruses invade a living cell and immediately exploit its machinery to replicate, herpesviruses and HIV have another option: They can wait patiently in a dormant state inside the cell until conditions become favorable. For example, human cytomegalovirus (HCMV), a member of the herpesvirus family, infects most of the world’s population, usually without causing disease, but when the immune system is weakened, the dormant virus can reawaken and cause severe infections. Moreover, HCMV is one of the most common infections passed from mother to fetus, and in a minority of cases it can cause serious harm, including developmental delays and hearing loss.
Among the hiding places for dormant cytomegalovirus in the body are blood-system cells called monocytes. ..."
From the abstract:
"Human cytomegalovirus (HCMV) infection results in either productive or latent infection, the latter enabling life-long viral persistence. Monocytes support latent infection but become permissive to productive infection upon differentiation into macrophages.
These differentiation-driven differences have been largely attributed to chromatin-mediated repression of the viral genome. Using metabolic labeling of newly synthesized RNA, we observe markedly lower viral transcription at early stages of infection in monocytes compared to macrophages.
Unbiased comparison reveals that this difference is partly explained by inefficient viral entry in monocytes: fewer viruses enter, and correspondingly, fewer genomes reach the nucleus. Indeed, ectopic expression of known HCMV entry receptors in monocytes enhances viral entry and enables productive infection, demonstrating that these cells can support full lytic replication if entry is efficient. We further identify integrin β3 as a differentiation-induced surface protein playing an important role in HCMV entry into macrophages, partially accounting for the observed differences in entry efficiency.
Finally, we show that cells receiving fewer viral genomes are the ones that establish latent infection and have the capacity to reactivate. Overall, our findings reveal that entry is a previously unrecognized factor contributing to latent infection in monocytes, adding a critical layer to the paradigm of HCMV latency."
Viral entry shapes HCMV latency establishment (open access)
Monocytes (left) and macrophages (right) one hour after exposure to cytomegalovirus virions (green), showing only a few individual virions in monocytes versus extensive viral entry into macrophages. Cell boundaries are shown in red and nuclei in blue
Fig. 1: HCMV infection and viral gene expression in monocytes and macrophages.
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