Maas, H. | bioRxiv Science

bioRxiv2022

PDGFRα+ fibroblasts are a major site of cytomegalovirus replication in vivo and genome maintenance during latency

To date, no herpesvirus has been shown to latently persist in fibroblastic cells. Here, we demonstrate that mouse CMV (MCMV), a {beta}-herpesvirus, persists for the long term and across organs in PDGFR+ fibroblastic cells, with similar or higher genome loads than in the previously known sites of MCMV latency. Whereas MCMV gene transcription in PDGFR+ fibroblastic cells was almost completely silenced at 5 months post-infection, these cells gave rise to reactivated virus ex vivo, arguing that they supported latent MCMV infection. Notably, PDGFR+ fibroblastic cells also supported productive virus replication during primary MCMV infection. Mechanistically, Stat1-deficiency resulted in increased lytic but abolished latent infection of fibroblastic cells in vivo. In sum, fibroblastic cells have a dual role as a site of lytic MCMV replication and a reservoir of latent MCMV in vivo and Stat1 is critically involved in the regulation of MCMV latency.

microbiology↗

bioRxiv2020

The underlying mechanisms of improved balance aftershort- and long-term training in older adults

Training improves balance control in older adults, but the time course and neural mechanisms underlying these improvements are unclear. We studied balance robustness and performance, H-reflex gains, paired reflex depression, and co-contraction duration in ankle muscles after one and ten training sessions in 22 older adults (+65yrs). Mediolateral balance robustness, time to balance loss in unipedal standing on a platform with decreasing rotational stiffness, improved (33%) after one session, with no further improvement after ten sessions. Balance performance, absolute mediolateral center of mass velocity, improved (18.75%) after one session in perturbed unipedal standing and (18.18%) after ten sessions in unperturbed unipedal standing. Co-contraction duration of soleus/tibialis anterior increased (16%) after ten sessions. H-reflex gain and paired reflex depression excitability did not change. H-reflex gains were lower, and soleus/tibialis anterior co-contraction duration was higher in participants with more robust balance after ten sessions, and co-contraction duration was higher in participants with better balance performance at several time-points. Changes in robustness and performance were uncorrelated with changes in co-contraction duration, H-reflex gain, or paired reflex depression. In older adults, balance robustness improved over a single session, while performance improved gradually over multiple sessions. Changes in co-contraction and excitability of ankle muscles were not exclusive causes of improved balance. HighlightsO_LIBalance robustness and balance performance in perturbed unipedal standing was improved after one balance training session, with no further improvement after ten sessions. C_LIO_LIBalance performance in unperturbed unipedal standing was improved after ten sessions C_LIO_LIH-reflex and paired reflex depression did not change after training in unipedal or bipedal standing. C_LIO_LICo-contraction duration of antagonistic ankle muscles increased after ten sessions in perturbed and unperturbed unipedal standing. C_LIO_LIChanges in co-contraction duration and excitability of ankle muscles were not exclusive causes of improved balance. C_LI

neuroscience↗