HCMV pUL135 remodels the actin cytoskeleton to impair immune recognition of infected cells.
Bottom Line: Without immune pressure, laboratory-adapted HCMV strains have undergone genetic alterations.Among these, the deletion of the UL/b' domain is associated with loss of virulence.An independent interaction between pUL135 and talin disrupted cell contacts with the extracellular matrix.
Affiliation: Institute of Infection & Immunity, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, UK. Electronic address: firstname.lastname@example.org.Show MeSH
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Mentions: pUL135 consistently induced cell rounding, loss of contact adhesions, and disassembly of stress fibers. RNA interference was used to investigate the roles played by the various pUL135-interacting cellular proteins (Figure S5A). Ablation of both ABI1 and ABI2 (ABI1/ABI2) was associated with a very slight reduction in F-actin levels in control cells, consistent with a requirement for ABI1/ABI2 in the WRC (Figures 5A andS5B). In contrast, pUL135 expression induced a very dramatic loss of F-actin. Moreover, following ABI1/ABI2 knockdown, pUL135 lost the capacity to depolymerize F-actin fibers throughout the center of the cell. This implies that, rather than directly inhibiting ABI1/ABI2, pUL135 is commandeering the WRC to actively promote F-actin depolymerization. To determine whether the entire WRC was involved in pUL135-mediated actin remodelling, the WRC member CYFIP1 was targeted with small interfering RNA (siRNA). Although knockdown had no obvious effect on actin, CYFIP1 was required for pUL135-mediated depolymerization of actin (Figures 5B and S5C). Therefore, ABI1/ABI2 was not the only WRC component necessary for pUL135-mediated actin remodelling.
Affiliation: Institute of Infection & Immunity, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, UK. Electronic address: email@example.com.