The herpes simplex virus 1 U_S3 regulates phospholipid synthesis

Herpes simplex virus type 1 capsids bud at nuclear and Golgi membranes for envelopment by phospholipid bilayers. In the absence of U_S3, nuclear membranes form multiple folds harboring virions that suggests disturbance in membrane turnover. Therefore, we investigated phospholipid metabolism in cells infected with the U_S3 deletion mutant R7041(ΔU_S3), and quantified membranes involved in viral envelopment. We report that (i) [³H]-choline incorporation into nuclear membranes and cytoplasmic membranes was enhanced peaking at 12 or 20h post inoculation with wild type HSV-1 and R7041(ΔU_S3), respectively, (ii) the surface area of nuclear membranes increased until 24h of R7041(ΔU_S3) infection forming folds that equaled ~45% of the nuclear surface, (iii) the surface area of viral envelopes between nuclear membranes equaled ~2400 R7041(ΔU_S3) virions per cell, and (iv) during R7041(ΔU_S3) infection, the Golgi complex expanded dramatically. The data indicate that U_S3 plays a significant role in regulation of membrane biosynthesis.