Herpes Simplex Virus Type 1 UL34 Gene Product Is Required for Viral Envelopment

ABSTRACT The herpes simplex virus type 1 UL34 gene encodes a protein that is conserved in all human herpesviruses. The association of the UL34 protein with membranes in the infected cell and its expression as a gamma-1 gene suggest a role in maturation or egress of the virus particle from the cell. To determine the function of this gene product, we have constructed a recombinant virus that fails to express the UL34 protein. This recombinant virus, in which the UL34 protein coding sequence has been replaced by green fluorescent protein, forms minute plaques and replicates in single-step growth experiments to titers 3 to 5 log orders of magnitude lower than wild-type or repair viruses. On Vero cells, the deletion virus synthesizes proteins of all kinetic classes in normal amounts. Electron microscopic and biochemical analyses show that morphogenesis of the deletion virus proceeds normally to the point of formation of DNA-containing nuclear capsids, but electron micrographs show no enveloped virus particles in the cytoplasm or at the surface of infected cells, suggesting that the UL34 protein is essential for efficient envelopment of capsids.

[1]  Y. Nishiyama,et al.  US3 protein kinase of herpes simplex virus type 2 plays a role in protecting corneal epithelial cells from apoptosis in infected mice. , 1999, The Journal of general virology.

[2]  A. Davison,et al.  The Herpes Simplex Virus Type 1 UL17 Gene Encodes Virion Tegument Proteins That Are Required for Cleavage and Packaging of Viral DNA , 1998, Journal of Virology.

[3]  B. Roizman,et al.  Herpes simplex virus 1 induces and blocks apoptosis at multiple steps during infection and protects cells from exogenous inducers in a cell-type-dependent manner. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[4]  D. McGeoch,et al.  The Genome Sequence of Herpes Simplex Virus Type 2 , 1998, Journal of Virology.

[5]  S. Weller,et al.  The Herpes Simplex Virus Type 1 Cleavage/Packaging Protein, UL32, Is Involved in Efficient Localization of Capsids to Replication Compartments , 1998, Journal of Virology.

[6]  P. Desai,et al.  , Not for Cleavage of Replicated Viral DNA 1 UL 25 Gene Is Required for Encapsidation but The Product of the Herpes Simplex Virus Type , 1998 .

[7]  C. Van Sant,et al.  The null mutant of the U(L)31 gene of herpes simplex virus 1: construction and phenotype in infected cells , 1997, Journal of virology.

[8]  H. Granzow,et al.  Functional complementation of UL3.5-negative pseudorabies virus by the bovine herpesvirus 1 UL3.5 homolog , 1997, Journal of virology.

[9]  B. Roizman,et al.  The product of ORF O located within the domain of herpes simplex virus 1 genome transcribed during latent infection binds to and inhibits in vitro binding of infected cell protein 4 to its cognate DNA site. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[10]  C. Van Sant,et al.  The herpes simplex virus 1 protein kinase US3 is required for protection from apoptosis induced by the virus. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[11]  S Jayachandra,et al.  Herpes simplex virus type 1 glycoprotein K is not essential for infectious virus production in actively replicating cells but is required for efficient envelopment and translocation of infectious virions from the cytoplasm to the extracellular space , 1997, Journal of virology.

[12]  B. Klupp,et al.  The UL20 gene product of pseudorabies virus functions in virus egress , 1997, Journal of virology.

[13]  G. A. Church,et al.  Study of herpes simplex virus maturation during a synchronous wave of assembly , 1997, Journal of virology.

[14]  B. Roizman,et al.  The γ134.5 protein of herpes simplex virus 1 complexes with protein phosphatase 1α to dephosphorylate the α subunit of the eukaryotic translation initiation factor 2 and preclude the shutoff of protein synthesis by double-stranded RNA-activated protein kinase , 1997 .

[15]  B. Roizman,et al.  The gamma(1)34.5 protein of herpes simplex virus 1 complexes with protein phosphatase 1alpha to dephosphorylate the alpha subunit of the eukaryotic translation initiation factor 2 and preclude the shutoff of protein synthesis by double-stranded RNA-activated protein kinase. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[16]  B. Roizman,et al.  Open reading frame P--a herpes simplex virus gene repressed during productive infection encodes a protein that binds a splicing factor and reduces synthesis of viral proteins made from spliced mRNA. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[17]  B. Klupp,et al.  Identification and characterization of the pseudorabies virus UL3.5 protein, which is involved in virus egress , 1996, Journal of virology.

[18]  D C Johnson,et al.  Herpes simplex virus glycoprotein K promotes egress of virus particles , 1995, Journal of virology.

[19]  N. de Wind,et al.  The US3-encoded protein kinase from pseudorabies virus affects egress of virions from the nucleus. , 1995, The Journal of general virology.

[20]  S. Brown,et al.  ICP34.5 influences herpes simplex virus type 1 maturation and egress from infected cells in vitro. , 1994, The Journal of general virology.

[21]  B. Roizman,et al.  Differential response of human cells to deletions and stop codons in the gamma(1)34.5 gene of herpes simplex virus , 1994, Journal of virology.

[22]  B. Roizman,et al.  A herpes simplex virus 1 US11-expressing cell line is resistant to herpes simplex virus infection at a step in viral entry mediated by glycoprotein D , 1994, Journal of virology.

[23]  A. Davison,et al.  A cosmid-based system for constructing mutants of herpes simplex virus type 1. , 1993, Virology.

[24]  J. Weir,et al.  Mutational analysis of the herpes simplex virus type 1 glycoprotein E promoter. , 1993, Virology.

[25]  S. Weller,et al.  Herpes simplex virus 1 alkaline nuclease is required for efficient egress of capsids from the nucleus. , 1993, Virology.

[26]  B. Roizman,et al.  Characterization of a temperature-sensitive mutant of the UL15 open reading frame of herpes simplex virus 1 , 1993, Journal of virology.

[27]  B. Roizman,et al.  The UL11 gene of herpes simplex virus 1 encodes a function that facilitates nucleocapsid envelopment and egress from cells , 1992, Journal of virology.

[28]  B. Roizman,et al.  UL34, the target of the herpes simplex virus U(S)3 protein kinase, is a membrane protein which in its unphosphorylated state associates with novel phosphoproteins , 1992, Journal of virology.

[29]  E. Telford,et al.  The DNA sequence of equine herpesvirus-1. , 1992, Virology.

[30]  B. Roizman,et al.  The herpes simplex virus 1 RNA binding protein US11 is a virion component and associates with ribosomal 60S subunits , 1992, Journal of virology.

[31]  B. Roizman,et al.  The UL20 gene of herpes simplex virus 1 encodes a function necessary for viral egress , 1991, Journal of virology.

[32]  B. Roizman,et al.  The herpes simplex virus 1 protein kinase encoded by the US3 gene mediates posttranslational modification of the phosphoprotein encoded by the UL34 gene , 1991, Journal of virology.

[33]  B. Roizman,et al.  Herpes simplex virus 1 RNA-binding protein US11 negatively regulates the accumulation of a truncated viral mRNA , 1991, Journal of virology.

[34]  C. Hutchison,et al.  The DNA sequence of the human cytomegalovirus genome. , 1991, DNA sequence : the journal of DNA sequencing and mapping.

[35]  F. Rixon,et al.  The herpes simplex virus UL33 gene product is required for the assembly of full capsids. , 1991, Virology.

[36]  D. Coen,et al.  A conserved open reading frame that overlaps the herpes simplex virus thymidine kinase gene is important for viral growth in cell culture , 1989, Journal of virology.

[37]  D. Leader,et al.  Herpes simplex virus 1 protein kinase is encoded by open reading frame US3 which is not essential for virus growth in cell culture , 1987, Journal of virology.

[38]  A J Davison,et al.  The complete DNA sequence of varicella-zoster virus. , 1986, The Journal of general virology.

[39]  R. Lerner,et al.  Identification by antibody to a synthetic peptide of a protein specified by a diploid gene located in the terminal repeats of the L component of herpes simplex virus genome , 1986, Journal of virology.

[40]  R. Everett,et al.  The product of gene US11 of herpes simplex virus type 1 is expressed as a true late gene. , 1986, The Journal of general virology.

[41]  A. Davison,et al.  Thymidine kinase deletion mutants of herpes simplex virus type 1. , 1982, The Journal of general virology.

[42]  B. Roizman,et al.  A generalized technique for deletion of specific genes in large genomes: a gene 22 of herpes simplex virus 1 is not essential for growth , 1981, Cell.

[43]  L. Moss,et al.  Herpesvirus Envelopment , 1968, Journal of virology.