Retroviral proteins that interact with the host cell cytoskeleton

Abstract

In the past decade, several lines of evidence have highlighted the importance of the host cell cytoskeleton in various stages of retroviral infection. To complete their lifecycle, retroviruses must penetrate the outer barrier of the cell membrane, and viral cores containing the viral genome must traverse the cytoplasm to the nucleus and then viral gene products must make the journey back to the cell surface in order to release new progeny. The presence of a dense cytoskeletal network and organelles in the cytoplasm creates an environment that greatly impedes diffusion of macromolecules such as viruses. As such, retroviruses have evolved means to hijack actin as well as microtubule cytoskeletal networks that regulate macromolecular movement within the host cell. Developing studies are discovering several host and viral factors that play important roles in retroviral trafficking.

Figure 1

A schematic view of the interaction of retroviruses with the host cytoskeleton throughout their replication cycle. The incoming viral cores are deposited in the cytoplasm after entry by fusion at the plasma membrane followed by penetration of cortical actin (X) or by endocytosis which bypasses the actin barrier. The incoming cores are then transported towards the nucleus by short-range actin-mediated movement. Subsequently, the RTCs and the PICs move along microtubule tracks utilizing dynein motors (indicated as green arrows) towards the MTOC. Following nuclear import, integration and generation of viral proteins, particle components are transported again along MTs (most likely utilizing KIF4 motor) to the plasma membrane where they are assembled with the viral genome and penetrate through cortical actin as immature particles. Maturation of virions leads to generation of infectious progeny containing several cytoskeletal regulatory proteins. Cellular cytoskeletal regulatory factors and the stages at which they interfere with the retroviral life cycle are indicated at the right hand side (factors in black affect both MLV and HIV-1; green indicates HIV-1 specific factors and blue are MLV specific factors). Retroviral proteins that interact with the cytoskeleton are indicated.