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: email@example.com.Show MeSH
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Mentions: The functional significance of the interaction of pUL135 with ABI1/ABI2 and talin in eliciting protection against NK cells was investigated with siRNA. The interaction with ABI1/ABI2, rather than talin, was critical for NK cell evasion whether assessed by CD107a mobilization (Figures 6A and 6B) or cytolysis assays (Figures 6C and 6D). This correlation was supported in experiments utilizing the characterized pUL135 deletion mutants. Only versions of pUL135 that bound ABI1/ABI2 elicited protection against NK cells (Figure 6E). Indeed, pUL135 functioned even more effectively as an NK evasion function when the talin-interacting domain was deleted. pUL135’s direct interaction with ABI1/ABI2 was not sufficient, a second WRC member (CYFIP1) was also required for pUL135 in order to induce protection against NK cell attack (Figure 6F). The recruitment of the entire WRC is thus implicated in pUL135 function. In the absence of pUL135, neither the ablation of ABI1/ABI2 nor CYFIP1 had an impact on NK cell recognition, indicating that pUL135 used ABI1/ABI2 to recruit the WRC and then subverted its activity to suppress NK cells.
Affiliation: Institute of Infection & Immunity, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, UK. Electronic address: firstname.lastname@example.org.