Herpes simplex virus capsid assembly and DNA packaging: a present and future antiviral drug target

2011 ◽  
Vol 19 (12) ◽  
pp. 606-613 ◽  
Author(s):  
Joel D. Baines
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Drug Target ◽  
Antiviral Drug ◽  
Dna Packaging ◽  
Capsid Assembly ◽  
Virus Capsid ◽  
Simplex Virus

scholarly journals Involvement of the Portal at an Early Step in Herpes Simplex Virus Capsid Assembly

2005 ◽  
Vol 79 (16) ◽  
pp. 10540-10546 ◽  
Author(s):  
William W. Newcomb ◽  
Fred L. Homa ◽  
Jay C. Brown
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Capsid Assembly ◽  
Assembly Process ◽  
Early Step ◽  
Virus Capsid ◽  
Capsid Formation ◽  
Simplex Virus ◽  
Unique Vertex

ABSTRACT DNA enters the herpes simplex virus capsid by way of a ring-shaped structure called the portal. Each capsid contains a single portal, located at a unique capsid vertex, that is composed of 12 UL6 protein molecules. The position of the portal requires that capsid formation take place in such a way that a portal is incorporated into one of the 12 capsid vertices and excluded from all other locations, including the remaining 11 vertices. Since initiation or nucleation of capsid formation is a unique step in the overall assembly process, involvement of the portal in initiation has the potential to cause its incorporation into a unique vertex. In such a mode of assembly, the portal would need to be involved in initiation but not able to be inserted in subsequent assembly steps. We have used an in vitro capsid assembly system to test whether the portal is involved selectively in initiation. Portal incorporation was compared in capsids assembled from reactions in which (i) portals were present at the beginning of the assembly process and (ii) portals were added after assembly was under way. The results showed that portal-containing capsids were formed only if portals were present at the outset of assembly. A delay caused formation of capsids lacking portals. The findings indicate that if portals are present in reaction mixtures, a portal is incorporated during initiation or another early step in assembly. If no portals are present, assembly is initiated in another, possibly related, way that does not involve a portal.

PGG impairs herpes simplex virus type 1 infection via blocking capsid assembly

2018 ◽  
Vol 13 (1) ◽  
pp. 17-32 ◽  
Author(s):  
Fan Luo ◽  
Junwei Liu ◽  
Yifei Wang ◽  
Mingfang Xu ◽  
Zhe Ren
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Capsid Assembly ◽  
Simplex Virus

scholarly journals Effects of Major Capsid Proteins, Capsid Assembly, and DNA Cleavage/Packaging on the pUL17/pUL25 Complex of Herpes Simplex Virus 1

2009 ◽  
Vol 83 (24) ◽  
pp. 12725-12737 ◽  
Author(s):  
Luella Scholtes ◽  
Joel D. Baines
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Nuclear Localization ◽  
Conformational Changes ◽  
Viral Proteins ◽  
Dna Packaging ◽  
Capsid Proteins ◽  
Herpes Simplex Virus 1 ◽  
Infected Cells ◽  
Simplex Virus

ABSTRACT The UL17 and UL25 proteins (pUL17 and pUL25, respectively) of herpes simplex virus 1 are located at the external surface of capsids and are essential for DNA packaging and DNA retention in the capsid, respectively. The current studies were undertaken to determine whether DNA packaging or capsid assembly affected the pUL17/pUL25 interaction. We found that pUL17 and pUL25 coimmunoprecipitated from cells infected with wild-type virus, whereas the major capsid protein VP5 (encoded by the UL19 gene) did not coimmunoprecipitate with these proteins under stringent conditions. In addition, pUL17 (i) coimmunoprecipitated with pUL25 in the absence of other viral proteins, (ii) coimmunoprecipitated with pUL25 from lysates of infected cells in the presence or absence of VP5, (iii) did not coimmunoprecipitate efficiently with pUL25 in the absence of the triplex protein VP23 (encoded by the UL18 gene), (iv) required pUL25 for proper solubilization and localization within the viral replication compartment, (v) was essential for the sole nuclear localization of pUL25, and (vi) required capsid proteins VP5 and VP23 for nuclear localization and normal levels of immunoreactivity in an indirect immunofluorescence assay. Proper localization of pUL25 in infected cell nuclei required pUL17, pUL32, and the major capsid proteins VP5 and VP23, but not the DNA packaging protein pUL15. The data suggest that VP23 or triplexes augment the pUL17/pUL25 interaction and that VP23 and VP5 induce conformational changes in pUL17 and pUL25, exposing epitopes that are otherwise partially masked in infected cells. These conformational changes can occur in the absence of DNA packaging. The data indicate that the pUL17/pUL25 complex requires multiple viral proteins and functions for proper localization and biochemical behavior in the infected cell.

scholarly journals In vitro antiviral and immunomodulatory activity of arbidol and structurally related derivatives in herpes simplex virus type 1-infected human keratinocytes (HaCat)

2014 ◽  
Vol 63 (11) ◽  
pp. 1474-1483 ◽  
Author(s):  
Brunella Perfetto ◽  
Rosanna Filosa ◽  
Vincenza De Gregorio ◽  
Antonella Peduto ◽  
Annalisa La Gatta ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Viral Infections ◽  
Antiviral Drug ◽  
Immunomodulatory Activity ◽  
Simplex Virus

Arbidol (ARB) is an antiviral drug that has broad-spectrum activity against a number of viral infections. To date, there are no specific data regarding its effects against a herpesvirus. Here, the in vitro antiviral effect of ARB and structurally related derivatives were evaluated in HaCat cells on different steps of herpes simplex virus type 1 replication: adsorption, entry and post-entry. The simplified pyrrolidine analogue, 9a2, showed the best antiviral activity in vitro by reducing the plaque numbers by about 50 % instead of 42 % obtained with ARB at the same concentration. Furthermore, we have reported that all tested compounds evaluated for their immunomodulatory activity showed the ability to reduce the viral proteins VP16 and ICP27 and to modify the virus-induced cytokine expression, allowing the host cell a more efficient antiviral response.

scholarly journals Disulfide Bond Formation Contributes to Herpes Simplex Virus Capsid Stability and Retention of Pentons

2011 ◽  
Vol 85 (17) ◽  
pp. 8625-8634 ◽  
Author(s):  
R. Szczepaniak ◽  
J. Nellissery ◽  
J. A. Jadwin ◽  
A. M. Makhov ◽  
A. Kosinski ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Disulfide Bond ◽  
Bond Formation ◽  
Disulfide Bond Formation ◽  
Virus Capsid ◽  
Simplex Virus ◽  
Capsid Stability

scholarly journals The UL25 Gene Product of Herpes Simplex Virus Type 1 Is Involved in Uncoating of the Viral Genome

2008 ◽  
Vol 82 (13) ◽  
pp. 6654-6666 ◽  
Author(s):  
Valerie G. Preston ◽  
Jill Murray ◽  
Christopher M. Preston ◽  
Iris M. McDougall ◽  
Nigel D. Stow
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Herpes Simplex Virus Type ◽  
Viral Genome ◽  
Dna Packaging ◽  
Nonpermissive Temperature ◽  
Viral Dna ◽  
Infected Cells ◽  
Simplex Virus

ABSTRACT Studies on the herpes simplex virus type 1 UL25-null mutant KUL25NS have shown that the capsid-associated UL25 protein is required at a late stage in the encapsidation of viral DNA. Our previous work on UL25 with the UL25 temperature-sensitive (ts) mutant ts1204 also implicated UL25 in a role at very early times in the virus growth cycle, possibly at the stage of penetration of the host cell. We have reexamined this mutant and discovered that it had an additional ts mutation elsewhere in the genome. The ts1204 UL25 mutation was transferred into wild-type (wt) virus DNA, and the UL25 mutant ts1249 was isolated and characterized to clarify the function of UL25 at the initial stages of virus infection. Indirect immunofluorescence assays and in situ hybridization analysis of virus-infected cells revealed that the mutant ts1249 was not impaired in penetration of the host cell but had an uncoating defect at the nonpermissive temperature. When ts1249-infected cells were incubated initially at the permissive temperature to allow uncoating of the viral genome and subsequently transferred to the restrictive temperature, a DNA-packaging defect was evident. The results suggested that ts1249, like KUL25NS, had a block at a late stage of DNA packaging and that the packaged genome was shorter than the full-length genome. Examination of ts1249 capsids produced at the nonpermissive temperature revealed that, in comparison with wt capsids, they contained reduced amounts of UL25 protein, thereby providing a possible explanation for the failure of ts1249 to package full-length viral DNA.

scholarly journals Herpes Simplex Virus Type 1 Portal Protein UL6 Interacts with the Putative Terminase Subunits UL15 and UL28

2003 ◽  
Vol 77 (11) ◽  
pp. 6351-6358 ◽  
Author(s):  
Colleen A. White ◽  
Nigel D. Stow ◽  
Arvind H. Patel ◽  
Michelle Hughes ◽  
Valerie G. Preston
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Dna Packaging ◽  
Mutant Proteins ◽  
Simplex Virus ◽  
In Cells ◽  
Hsv 1

ABSTRACT The herpes simplex virus type 1 (HSV-1) UL6, UL15, and UL28 proteins are essential for cleavage of replicated concatemeric viral DNA into unit length genomes and their packaging into a preformed icosahedral capsid known as the procapsid. The capsid-associated UL6 DNA-packaging protein is located at a single vertex and is thought to form the portal through which the genome enters the procapsid. The UL15 protein interacts with the UL28 protein, and both are strong candidates for subunits of the viral terminase, a key component of the molecular motor that drives the DNA into the capsid. To investigate the association of the UL6 protein with the UL15 and UL28 proteins, the three proteins were produced in large amounts in insect cells with the baculovirus expression system. Interactions between UL6 and UL28 and between UL6 and UL15 were identified by an immunoprecipitation assay. These results were confirmed by transiently expressing wild-type and mutant proteins in mammalian cells and monitoring their distribution by immunofluorescence. In cells expressing the single proteins, UL6 and UL15 were concentrated in the nuclei whereas UL28 was found in the cytoplasm. When the UL6 and UL28 proteins were coexpressed, UL28 was redistributed to the nuclei, where it colocalized with UL6. In cells producing either of two cytoplasmic UL6 mutant proteins and a functional epitope-tagged form of UL15, the UL15 protein was concentrated with the mutant UL6 protein in the cytoplasm. These observed interactions of UL6 with UL15 and UL28 are likely to be of major importance in establishing a functional DNA-packaging complex at the portal vertex of the HSV-1 capsid.

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