Virus replication in infected epithelial cells is coupled to cell shape-responsive metabolic controls

Area of Science:

• Cell Biology
• Virology
• Biochemistry

Background:

• Cell shape and spreading are critical for cellular functions.
• Substrate adhesiveness influences cell morphology and behavior.
• Understanding cell metabolism's response to physical cues is essential.

Purpose of the Study:

• To investigate the impact of altered cell shape on cellular macromolecular metabolism.
• To examine how changes in cell spreading affect viral replication.
• To determine if cell shape-induced metabolic restrictions influence virus-host interactions.

Main Methods:

• Monkey epithelial cells were cultured on poly (HEMA) films of varying thickness to control substrate adhesiveness and cell shape.
• Cellular macromolecular synthesis (DNA, RNA, protein) was quantified.
• Cells were infected with SV40, herpes virus, or VSV to assess viral replication.

Main Results:

• Reduced cell spreading and spheroidal shape significantly inhibited DNA and RNA synthesis (>95%) within 14-16 hours.
• Protein synthesis showed a less pronounced reduction (twofold) after 24 hours.
• SV40 and herpes virus replication were inhibited in parallel with cellular metabolism.
• Vesicular stomatitis virus (VSV) could replicate in the cytoplasm when nuclear activity was inhibited by altered cell shape.

Conclusions:

• Cell shape and spreading significantly regulate nuclear macromolecular metabolism in epithelial cells.
• These cell shape-induced metabolic restrictions are a dominant factor that inhibits viral replication.
• Virus replication is dependent on and limited by the host cell's metabolic state, which can be modulated by cell morphology.