Synthesis and Packaging of Herpes Simplex Virus DNA in the Course of Virus Passages at High Multiplicity

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Abstract
Herpes simplex virus type 1 (HSV-1), strain ANG, was passaged serially at high MOI or undiluted on RC-37 cells. The yields of infectious virus decreased and increased periodically with a maximum of about 3 log units variation in titer. The amount of newly synthesized HSV-1 DNA, however, did not vary by more than a factor of 2. On the other hand, the fraction of total HSV-1 DNA associated with virions was reduced at passage numbers coinciding with the minima in the yields of infectious progeny virus. Apparently, low yields of infectious virus mainly reflected a reduced efficiency of packaging of viral DNA into mature virus particles. One step in the process of virus maturation which appeared to be impaired was the assembly of nucleocapsids. HSV-1 ANG was shown to be capable of generating different classes of defective particles in independent series of virus passages at high MOI.