The role of microtubules changes during the course of infection. During early infection microtubules seem to act as scaffolding for the localized attachment and subsequent release and movement of VRCs along the ER. At later stages of infection, in cells behind the infection front, the microtubules act as a scaffold, along which anchored VRCs grow and mature into inclusions or X–bodies that harbor virus factories and produce virus progeny. At even later stages the microtubules may accumulate MP along their length (Figures 2 and 3). The accumulation of MP along the length of microtubules is not required for virus movement, as this phenomenon usually occurs in cells far behind the leading front of infection (Padgett et al., 1996; Heinlein et al., 1998a). Consistently, downregulating microtubule alignment of accumulated MP by knocking down the expression of MPB2C had no consequence on MP function in virus movement (Curin et al., 2007), and a virus variant (R3) that shows reduced accumulation along microtubules exhibited faster, rather than slower, cell-to-cell movement (Gillespie et al., 2002). The observation of microtubule-aligned MP is indeed variable, and depends on the nature of the host for infection (Padgett et al., 1996), the virus variant under study (Padgett et al., 1996; Heinlein et al., 1998a; Gillespie et al., 2002) and on environmental conditions (Boyko et al., 2000b). Nevertheless, the accumulation of MP along microtubules causes microtubule stabilization (Boyko et al., 2000a; Ashby et al., 2006; Ferralli et al., 2006), and interferes with kinesin motility (Ashby et al., 2006), intracellular MP particle/VRC movements (Boyko et al., 2007) as well as with intercellular virus spread (Curin et al., 2007), and thus may play an important role in prohibiting further virus movement between cells that are already behind the advancing front of virus infection. As the alignment of accumulated MP along microtubules precedes the sudden disappearance of the MP during even later stages, i.e. in the center of infection sites, MP-aligned microtubules may also be associated with a pathway leading to the degradation of the MP by the 26S proteasome (Padgett et al., 1996; Heinlein et al., 1998a; Reichel and Beachy, 2000). This hypothesis is supported by the increased stability of the R3 MP, showing decreased accumulation along the polymer (Gillespie et al., 2002); however, several observations argue against a direct role of microtubules in MP degradation. First, the MP is still degraded in the center of infection sites upon treatment of the leaves with the microtubule-disrupting agent APM (Ashby et al., 2006); second, an MP mutant with increased microtubule binding was more stable than the wild-type MP in infected tobacco BY–2 protoplasts (Kotlizky et al., 2001); and, third, unlike the MP in crude extracts, microtubule-associated MP is not ubiquitinated (Ashby et al., 2006). Our recent studies indicate that the degradation of the MP depends on the AAA ATPase activity of CDC48 (Niehl et al., 2012). This protein is induced by infection, binds and extracts the MP from ER inclusions and allows the degradation of the protein in the cytosol by an ER-associated degradation (ERAD)-like mechanism. Overexpression of the protein enhanced the accumulation of MP along microtubules, which may suggest a role of microtubules in stockpiling the MP before degradation. Recent studies demonstrate that ERAD substrates are de-ubiquitinated for dislocation from the ER (Ernst et al., 2011; Tsai and Weissman, 2011), which could explain the lack of ubiquitination of microtubule-aligned MP (Ashby et al., 2006). Whether microtubule-aligned MP is re-ubiquitinated for subsequent degradation, or whether this fraction of the MP enters yet another pathway before degradation, remains to be investigated.