The myristylated virion proteins of herpes simplex virus type 1: investigation of their role in the virus life cycle

MacLean, Christine A.; Dolan, Aidan; Jamieson, Fiona E.; McGeoch, Duncan J.

doi:10.1099/0022-1317-73-3-539

Cited by 61 publications

(72 citation statements)

References 40 publications

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“…In HCMV, the pUL11 homolog pUL99 has been found to interact with the pUL16 homolog pUL94 (Liu et al, 2009). Consistent with the previously described model of capsid transport and budding, herpesviruses lacking pUL16, pUL21 or pUL11 (or their homologs) have defects in virus egress, resulting in decreased amounts of extracellular viruses produced and the accumulation of non-enveloped capsids in the cytoplasm (MacLean et al, 1989(MacLean et al, , 1992Baines and Roizman, 1992;Baines et al, 1994;Kopp et al, 2003;Schimmer and Neubauer, 2003;Silva et al, 2003;Britt et al, 2004;Jones and Lee, 2004;Silva et al, 2005;Seo and Britt, 2006;Guo et al, 2009).…”

Section: Secondary Envelopmentsupporting

confidence: 61%

Role of tegument proteins in herpesvirus assembly and egress

et al. 2010

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Morphogenesis and maturation of viral particles is an essential step of viral replication. An infectious herpesviral particle has a multilayered architecture, and contains a large DNA genome, a capsid shell, a tegument and an envelope spiked with glycoproteins. Unique to herpesviruses, tegument is a structure that occupies the space between the nucleocapsid and the envelope and contains many virus encoded proteins called tegument proteins. Historically the tegument has been described as an amorphous structure, but increasing evidence supports the notion that there is an ordered addition of tegument during virion assembly, which is consistent with the important roles of tegument proteins in the assembly and egress of herpesviral particles. In this review we first give an overview of the herpesvirus assembly and egress process. We then discuss the roles of selected tegument proteins in each step of the process, i.e., primary envelopment, deenvelopment, secondary envelopment and transport of viral particles. We also suggest key issues that should be addressed in the near future.

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Section: Secondary Envelopmentsupporting

confidence: 61%

Role of tegument proteins in herpesvirus assembly and egress

et al. 2010

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“…UL11 is conserved across alpha-, beta-, and gammaherpesviruses and plays an essential role in virion envelopment and egress (129)(130)(131)(132). The C terminus of UL11 normally interacts with glycoprotein E (gE; US8) (133,134).…”

Section: Resultsmentioning

confidence: 99%

Evolution and Diversity in Human Herpes Simplex Virus Genomes

Szpara

Gatherer

Ochoa

et al. 2014

J Virol

199

280

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gHerpes simplex virus 1 (HSV-1) causes a chronic, lifelong infection in >60% of adults. Multiple recent vaccine trials have failed, with viral diversity likely contributing to these failures. To understand HSV-1 diversity better, we comprehensively compared 20 newly sequenced viral genomes from China, Japan, Kenya, and South Korea with six previously sequenced genomes from the United States, Europe, and Japan. In this diverse collection of passaged strains, we found that one-fifth of the newly sequenced members share a gene deletion and one-third exhibit homopolymeric frameshift mutations (HFMs). Individual strains exhibit genotypic and potential phenotypic variation via HFMs, deletions, short sequence repeats, and single-nucleotide polymorphisms, although the protein sequence identity between strains exceeds 90% on average. In the first genome-scale analysis of positive selection in HSV-1, we found signs of selection in specific proteins and residues, including the fusion protein glycoprotein H. We also confirmed previous results suggesting that recombination has occurred with high frequency throughout the HSV-1 genome. Despite this, the HSV-1 strains analyzed clustered by geographic origin during whole-genome distance analysis. These data shed light on likely routes of HSV-1 adaptation to changing environments and will aid in the selection of vaccine antigens that are invariant worldwide. Herpes simplex virus 1 (HSV-1; species Human herpesvirus 1, genus Simplexvirus, subfamily Alphaherpesvirinae, family Herpesviridae, order Herpesvirales) is among the most successful human pathogens in terms of its global distribution, longevity in the host, and mild symptoms among the great majority of those exposed (1-4). HSV-1 is a large, enveloped DNA virus that infects lytically at epithelial surfaces and establishes a lifelong, latent infection in sensory neurons. HSV-1 infection produces a wide range of symptoms, ranging from few or none in many seropositive individuals to periodic lesions on epithelial surfaces in a significant proportion of people and to lethal encephalitis as an extreme manifestation in a few. There is no vaccine at present (5, 6). Studies in animal models have characterized the ways in which genetic variation between viral strains can influence the symptoms of pathology, including lesion severity and rates of reactivation from latency. The most recent phase III vaccine trial for HSV failed to provide protection from infection (7, 8), and one contributing factor to this failure may well be variation among HSV isolates found in the field.Based on early restriction fragment length polymorphism (RFLP) analyses, HSV-1 has been described as more diverse than HSV-2 (9-11). In contrast to both HSV-1 and HSV-2, the related human alphaherpesvirus, varicella-zoster virus (VZV), has relatively low interstrain diversity (12-15). Decades of research comparing RFLP bands, polypeptide size, and PCR-based sequence analysis have revealed that HSV-1 strains vary between individuals, over sequential isolates from the s...

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“…Like other alphaherpesvirus homologs, HSV-1 UL11 is thought to play a role in nucleocapsid envelopment and egress; however, the specific functions of this protein are unknown (3,21,25,35). Consistent with a role in budding at cytoplasmic locations, UL11 localizes primarily to the Golgi apparatus when expressed in the absence of other viral proteins (5).…”

mentioning

confidence: 85%

Binding Partners for the UL11 Tegument Protein of Herpes Simplex Virus Type 1

Loomis

Courtney

Wills

2003

J Virol

102

186

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The product of the U L 11 gene of herpes simplex virus type 1 (HSV-1) is a 96-amino-acid tegument protein that accumulates on the cytoplasmic face of internal membranes. Although it is thought to be important for nucleocapsid envelopment and egress, the actual function of this protein is unknown. Previous studies focused on the characterization of sequence elements within the UL11 protein that function in membrane binding and trafficking to the Golgi apparatus. Binding was found to be mediated by two fatty acyl groups (myristate and palmitate), while an acidic cluster and a dileucine motif were identified as being important for the recycling of UL11 from the plasma membrane to the Golgi apparatus. The goal of the experiments described here was to identify and characterize binding partners (viral or cellular) of UL11. Using both immunoprecipitation and glutathione S-transferase (GST) pull-down assays, we identified a 40-kDa protein that specifically associates with UL11 from infected Vero cells. Mutational analyses revealed that the acidic cluster and the dileucine motif are required for this association, whereas the entire second half of UL11 is not. In addition, UL11 homologs from pseudorabies and Marek's disease herpesviruses were also found to be capable of binding to the 40-kDa protein from HSV-1-infected cells, suggesting that the interaction is conserved among alphaherpesviruses. Purification and analysis of the 40-kDa protein by mass spectrometry revealed that it is the product of the U L 16 gene, a virion protein reported to be involved in nucleocapsid assembly. Cells transfected with a UL16-green fluorescent protein expression vector produced a protein that was of the expected size, could be pulled down with GST-UL11, and accumulated in a Golgi-like compartment only when coexpressed with UL11, indicating that the interaction does not require any other viral products. These data represent the first steps toward elucidating the network of tegument proteins that UL11 links to membranes.During herpes simplex virus type 1 (HSV-1) assembly, over 30 different proteins come together to form three major structures: the nucleocapsid, the glycoprotein-containing envelope, and the collection of proteins located between the capsid and the envelope, known as the tegument (33). As with other herpesviruses, the most recent model for HSV-1 envelopment suggests that assembled nucleocapsids are shuttled out of the nucleus by budding and fusion events on the inner and outer nuclear membranes, respectively, and then travel through the cytoplasm until reaching trans-Golgi network (TGN)-derived vesicles (reviewed in reference 27). At this site, nucleocapsids are thought to acquire their final lipid bilayer in a process that also results in the acquisition of the tegument and glycoproteins. The mature virions subsequently follow the secretory pathway out to the cell surface, where they are released into the extracellular medium. Although several lines of evidence support this model, the specific molecular mechanisms by which t...

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The myristylated virion proteins of herpes simplex virus type 1: investigation of their role in the virus life cycle

Cited by 61 publications

References 40 publications

Role of tegument proteins in herpesvirus assembly and egress

Role of tegument proteins in herpesvirus assembly and egress

Evolution and Diversity in Human Herpes Simplex Virus Genomes

Binding Partners for the UL11 Tegument Protein of Herpes Simplex Virus Type 1

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