Nuclear pore composition and gating in herpes simplex virus-infected cells

Area of Science:

• Virology
• Cell Biology
• Molecular Biology

Background:

• The mechanism of herpes simplex virus (HSV) nuclear egress is controversial.
• One proposed route involves direct passage through altered nuclear pores, while the accepted model suggests envelopment and fusion.

Purpose of the Study:

• To investigate the biochemical composition and functional integrity of nuclear pores during HSV infection.
• To determine if HSV infection leads to gross morphological alterations or functional gating defects in nuclear pores.

Main Methods:

• Biochemical analysis of nucleoporins in infected and uninfected cells.
• Density gradient sedimentation of nuclear pore components.
• Functional assays using microinjected dextran beads in live cells.
• Tracking infection progression with a recombinant GFP-VP16 expressing virus.

Main Results:

• Total levels and sedimentation patterns of major nucleoporins remained largely unchanged up to 18 hours post-infection.
• Minor alterations in Nup358/RanBP2 modification (O-glycosylation) were observed.
• The nuclear permeability barrier for molecules >70 kDa remained intact in live-cell functional assays.

Conclusions:

• The study found no evidence for gross nuclear pore perturbation or loss of gating function during HSV infection.
• While a small population of modified pores cannot be excluded, the findings challenge the hypothesis of direct capsid exit through significantly altered pores.