Coupling viruses to dynein and kinesin-1

Abstract

It is now clear that transport on microtubules by dynein and kinesin family motors has an important if not critical role in the replication and spread of many different viruses. Understanding how viruses hijack dynein and kinesin motors using a limited repertoire of proteins offers a great opportunity to determine the molecular basis of motor recruitment. In this review, we discuss the interactions of dynein and kinesin-1 with adenovirus, the α herpes viruses: herpes simplex virus (HSV1) and pseudorabies virus (PrV), human immunodeficiency virus type 1 (HIV-1) and vaccinia virus. We highlight where the molecular links to these opposite polarity motors have been defined and discuss the difficulties associated with identifying viral binding partners where the basis of motor recruitment remains to be established. Ultimately, studying microtubule-based motility of viruses promises to answer fundamental questions as to how the activity and recruitment of the dynein and kinesin-1 motors are coordinated and regulated during bi-directional transport.

Figure 1

Schematic representation of the subunit composition of dynein and kinesin-1. (A) The motor containing cytoplasmic dynein heavy chains are shown in orange and associated intermediate and light chains in shades of blue. The motor domain is composed of six AAA ATPase domains arranged in a hexameric ring from which a microtubule binding stalk projects. The N-terminal tail of the heavy chain mediates its dimerization and contains the binding sites for two intermediate chains (ICs) and two light intermediate chains (LICs). The two intermediate chains (ICs) also interact with three pairs of light chains: Tctex, LC7 and LC8. (B) Kinesin-1 is a heterotetramer composed of two motor containing heavy chains (orange) and two light chains (blue). The microtubule binding motor domain is found in the N-terminus of the heavy chain. The light chains associate with the heavy chains via heptad repeat regions in their N-terminus. The C-terminal half of the light chains is composed of six tetratricopeptide repeats (TPR), which represent cargo binding domains.

Figure 2

Transport of herpes virus during entry and egress. ENTRY: Depending on the cell type, viruses enter by (A) directly fusing with the plasma membrane or (B) via an endocytic-based mechanism. Regardless of the mode of entry, viruses within endosomes or more usually as non-enveloped capsids probably recruit both kinesin and dynein even though they move in net retrograde (minus end) direction along microtubules towards the nucleus. Depending on the position MTOC and organization of the microtubule cytoskeleton relative to the nucleus, it is also possible that kinesin-1-dependent plus-end directed movement along microtubules (C) may be required for the virus to reach the nuclear envelope. EGRESS: Following their exit from the nucleus, the tegument of non-enveloped capsids recruits kinesin-1 and dynein to facilitate their bidirectional transport on microtubules (D, E). Viruses will move along microtubules until they encounter membrane compartments into which they can bud to form enveloped virions (F, G). The location of these membrane compartments will vary depending on the position of the MTOC and organization of the microtubule cytoskeleton, which will be cell type dependent. Consequently, viral movements towards these membrane compartment may require a net minus-end (dynein) or plus-end (kinesin-1) driven transport depending on the site of envelopment (F, G) with respect to the MTOC. Some viruses, however, may never encounter the right membrane compartment and will continue to move as non-enveloped capsids throughout the cell (E, H). After envelopment, viruses within vesicular compartments (I) will be transported in a net anterograde manner, possibly by kinesin-1, towards the plasma membrane, where they fuse and are released.

Figure 3

Vaccinia IEV recruit kinesin-1 and move on microtubules. (A) Immunofluorescence images showing recruitment of kinesin-1 (RFP–KLC, red) to vaccinia IEV (blue) associated with microtubules (green). (B) Stills taken from live cell imaging of the movement of YFP-tagged vaccinia IEV in cells expressing RFP-tagged kinesin light chain 2. The time in seconds is indicated and the right panel shows a maximum intensity projection to highlight the path taken by the virus.