Ultrastructural analysis of the interaction between F-actin and respiratory syncytial virus during virus assembly

Chris E Jeffree1, Gaie Brown, Jim Aitken

  • 1School of Biological Sciences, Daniel Rutherford Building, King's Buildings, Mayfield Road, University of Edinburgh Edinburgh, EH9 3JH, UK.

Virology
|September 11, 2007
PubMed

Insights

Respiratory syncytial virus (RSV) interacts closely with filamentous actin (F-actin) early in infection. An F-actin signaling pathway involving phosphatidyl-3-kinase (PI3K) and Rac GTPase is crucial for RSV assembly.

Area of Science:

  • Virology
  • Cell Biology
  • Molecular Biology

Background:

  • Respiratory syncytial virus (RSV) is a major cause of respiratory illness in infants and young children.
  • The interaction between viruses and the host cell cytoskeleton is critical for viral replication and assembly.
  • Filamentous actin (F-actin) plays diverse roles in cellular processes, including viral infection.

Purpose of the Study:

  • To investigate the physical interaction between RSV and F-actin during infection.
  • To elucidate the role of F-actin-associated signaling pathways in RSV assembly.

Main Methods:

  • Observational studies of RSV-infected cells to detect F-actin and virus interactions.
  • Treatment of infected cells with specific inhibitors of phosphatidyl-3-kinase (PI3K) and Rac GTPase.
  • Analysis of viral protein expression, glycoprotein trafficking, and virus filament formation.

Main Results:

  • A close physical association between F-actin and RSV was observed early in infection (from 8 h post-infection).
  • Inhibition of PI3K using LY294002 blocked the formation of RSV filaments but did not affect viral protein expression or glycoprotein surface transport.
  • Inhibition of Rac GTPase using NSC23766 yielded similar results, indicating its involvement downstream of PI3K.

Conclusions:

  • RSV exhibits an intimate interaction with F-actin during infection.
  • The F-actin-associated signaling pathway, involving PI3K and Rac GTPase, plays a significant role in RSV assembly.

Related Concept Videos

Respiratory Syncytial Virus Disease01:29

Respiratory Syncytial Virus Disease

Human respiratory syncytial virus (RSV) is a widespread pathogen that primarily targets infants and young children but also poses a serious health risk to elderly and immunocompromised individuals. Belonging to the Pneumoviridae family, RSV is a negative-sense, single-stranded RNA virus within the Pneumovirus genus. Its global health burden is significant, with millions of cases annually resulting in hospitalizations and mortality, particularly in resource-limited settings. Although most...
Generation of Straight or Branched Actin Filaments01:14

Generation of Straight or Branched Actin Filaments

The straight or branched structure formation of actin filaments is controlled by nucleating proteins such as the formins and Arp2/3 complex. Formin-mediated assembly results in straight filaments, whereas Arp2/3 protein complex-mediated assembly results in branched actin filaments.
Arp2/3 Complex
Arp2/3 complex is a seven-subunit complex consisting of two proteins similar to actin- Arp2 and Arp3, and five other subunits that help keep Arp2 and Arp3 inactive. When required, the complex is...
Protein Complex Assembly02:41

Protein Complex Assembly

Proteins can form homomeric complexes with another unit of the same protein or heteromeric complexes with different types.  Most protein complexes self-assemble spontaneously via ordered pathways, while some proteins need assembly factors that guide their proper assembly. Despite the crowded intracellular environment, proteins usually interact with their correct partners and form functional complexes.
Many viruses self-assemble into a fully functional unit using the infected host cell to...
Mechanism of Filopodia Formation01:39

Mechanism of Filopodia Formation

Filopodia are thin, actin-rich cellular protrusions that play an important role in many fundamental cellular functions. They vary in their occurrence, length, and positioning in different cell types, suggesting their diverse roles.
Their main function is to guide migrating cells during normal tissue morphogenesis or cancer metastasis by recognizing and making initial contacts with the extracellular matrix. However, they can also act as stationary cell anchors or help to establish communication...
Assembly of Cytoskeletal Filaments01:18

Assembly of Cytoskeletal Filaments

Cytoskeletal filaments are polymeric forms of smaller protein subunits. However, individual cytoskeletal filaments may easily disassemble or associate with other similar filaments to form rigid structures. Microfilaments, made of actin monomers, rely on actin-binding proteins to form bundles and create networks of individual actin filaments. Microtubules rely on microtubule-associated proteins (MAPs) to form sturdy cylindrical structures. However, the proteins involved in forming complex...
Formation of Higher-order Actin Filaments01:11

Formation of Higher-order Actin Filaments

The polymerization of G-actin monomers into filamentous F-actin is a multi-step process. Once the F-actins are formed, they can bundle together in different arrangements to form higher-order networks and regulate cellular functions. Common examples include the formation of lamellipodia and filopodia at the cell's leading edge by actin reorganization in a migrating cell. The microvilli on the brush border epithelial cells are also formed through the F-actin network.
The high-order actin networks...