The UL11 gene of herpes simplex virus 1 encodes a function that facilitates nucleocapsid envelopment and egress from cells.
The UL11 gene of herpes simplex virus 1 was reported to encode a myristylated protein (C. A. MacLean, B. Clark, and D. J. McGeoch, J. Gen. Virol. 70:3147-3157, 1989). To determine the function of the gene product, a recombinant virus (R7219) lacking 61% of the codons (176 bp of the 288-bp coding domain) was genetically engineered. The deletion mutant replicated in all cell lines tested, albeit to titers 30- to 250-fold lower than those obtained from cells infected with wild-type virus. Electron microscopic analyses indicated that both full and empty capsids accumulated in the nuclei, juxtaposed with the inner lamellae of the nuclear membranes, and that increased numbers of naked particles were present in the cytoplasm of cells infected with the mutant virus. There was a greater than 1,000-fold decrease in the amount of infectious extracellular virus released from Vero cells infected with the deletion mutant compared with that from cells infected with wild-type virus. Furthermore, the onset of release of infectious virus from cells infected with the UL11- mutant was significantly delayed: levels of extracellular UL11- virus increased 15-fold between 20 and 26 h after infection, while levels of wild-type extracellular virus increased 500-fold between 8 and 14 h after infection. A virus in which the UL11 gene was restored produced wild-type levels of total and extracellular virus and was indistinguishable from wild-type virus upon analysis by electron microscopy. Taken together, the data indicate that the absence of the UL11 gene causes a reduced capacity to envelope and transport virions into the extracellular space.
Baines
J D
JD
Marjorie B. Kovler Viral Oncology Laboratory, University of Chicago, Illinois 60637.
Roizman
B
B
D000818:Animals; D002213:Capsid / Q000032:analysis / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D002460:Cell Line; D002478:Cells, Cultured; D002872:Chromosome Deletion; D004279:DNA, Viral / Q000032:analysis / Q000235:genetics / Q000648:ultrastructure; D005814:Genes, Viral; D006801:Humans; D008854:Microscopy, Electron; D009685:Nuclear Envelope / Q000382:microbiology / Q000648:ultrastructure; D011817:Rabbits; D011995:Recombination, Genetic; D018139:Simplexvirus / Q000235:genetics* / Q000648:ultrastructure; D012867:Skin; D013937:Thymidine Kinase / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D014709:Vero Cells; D014758:Viral Core Proteins / Q000235:genetics / Q000378:metabolism*
D004279:DNA, Viral; D014758:Viral Core Proteins; D013937:Thymidine Kinase