Microtubule Regulation and Function during Virus Infection

Abstract

Microtubules (MTs) form a rapidly adaptable network of filaments that radiate throughout the cell. These dynamic arrays facilitate a wide range of cellular processes, including the capture, transport, and spatial organization of cargos and organelles, as well as changes in cell shape, polarity, and motility. Nucleating from MT-organizing centers, including but by no means limited to the centrosome, MTs undergo rapid transitions through phases of growth, pause, and catastrophe, continuously exploring and adapting to the intracellular environment. Subsets of MTs can become stabilized in response to environmental cues, acquiring distinguishing posttranslational modifications and performing discrete functions as specialized tracks for cargo trafficking. The dynamic behavior and organization of the MT array is regulated by MT-associated proteins (MAPs), which include a subset of highly specialized plus-end-tracking proteins (ϩTIPs) that respond to signaling cues to alter MT behavior. As pathogenic cargos, viruses require MTs to transport to and from their intracellular sites of replication. While interactions with and functions for MT motor proteins are well characterized and extensively reviewed for many viruses, this review focuses on MT filaments themselves. Changes in the spatial organization and dynamics of the MT array, mediated by virus-or host-induced changes to MT regulatory proteins, not only play a central role in the intracellular transport of virus particles but also regulate a wider range of processes critical to the outcome of infection.KEYWORDS virus, cytoskeleton, microtubules, nucleation, microtubule-associated proteins, plus-end-tracking proteins T he dense cytosolic environment poses a major barrier to the free movement of macromolecules, making microtubule (MT)-based transport a critical aspect of virus replication. Indeed, almost as soon as these filaments were identified and characterized, virus particles were observed proximal to "microtubuli," with evidence that MTassociated proteins (MAPs) might mediate this association. Chemicals that disrupt MT networks, still commonly used today, were reported to suppress virus infection. Moreover, either infection or expression of viral proteins was observed to alter the organization of these networks, suggesting that MTs not only facilitated infection but were also likely to be actively manipulated by viruses. In subsequent decades an enormous body of work helped unravel how virus particles exploit MT motors to traffic within infected cells, and we direct readers to a recent review of this subject (1). Here, we discuss recent advances in our understanding of how MTs themselves are regulated and function during infection, limiting this minireview to some illustrative examples in each case. TWO ENDS TO THE STORY: THE BASICS OF MT POLARITY AND ORGANIZATIONMTs form through the polymerization of ␣/␤-tubulin heterodimers into polarized filaments that have minus and plus ends (Fig. 1A and B). MTs nucleate through minus-end seeding at MT-organizing cen...

Imaging the adenovirus infection cycle

“…Rapid intracytosolic cargo transport often occurs along microtubules (MTs) using dynein motor complexes on minus‐end MTs toward the nucleus or kinesin motor complexes on plus‐end MTs to the cell periphery . AdC2 or AdC5 was shown under EM to bind MTs in the cytosol as membrane‐free particles .…”

Microtubule-Dependent Trafficking of Alphaherpesviruses in the Nervous System: The Ins and Outs

“…Association of dynactin with the incoming alphaherpesvirus capsid [64,68,69] is likely to contribute to the processivity of dynein-mediated retrograde motion [66,71], but it may also mediate attachment of capsids to the plus ends of MTs by connecting them to the EB1/CLIP-170 (end-binding protein 1/cytoplasmic linker protein 170) complex [72,73]. EB1 is a +TIP (plus-end-tracking protein) that recognizes the growing ends of dynamic MTs and recruits other regulatory +TIPS to them [74,75].…”

Bovine Foamy Virus: Shared and Unique Molecular Features In Vitro and In Vivo

“…Viruses must engage bidirectional cellular transport mechanisms for completing their whole life cycle, and many viruses require microtubules (MTs) during cell entry for efficient nuclear targeting or the cytosolic transport of naked viral particles [70][71][72]. In BFV, co-localization of MTs and assembling viral particles was clearly observed in BFV infected cells, which implied that BFV particles or assembly intermediates may transport along the cellular MTs to the cellular membrane to ultimately egress from the host cell.…”