Retention of Nonlinear Viral DNA during Herpes simplex Virus Latency in vitro

Intervirology ◽  
1991 ◽  
Vol 32 (2) ◽  
pp. 69-75 ◽  
Author(s):  
Chris M. Preston ◽  
Jackie Russell
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Viral Dna ◽  
Virus Latency ◽  
Simplex Virus

The Essential in Vivo Function of the Herpes Simplex Virus UL42 Protein Correlates with Its Ability to Stimulate the Viral DNA Polymerase in Vitro

Virology ◽  
1994 ◽  
Vol 200 (2) ◽  
pp. 447-456 ◽  
Author(s):  
Peter J. Reddig ◽  
Lynn A. Grinstead ◽  
Steven J. Monahan ◽  
Paul A. Johnson ◽  
Deborah S. Parris
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Dna Polymerase ◽  
Viral Dna ◽  
Simplex Virus

scholarly journals Role of the UL25 Protein in Herpes Simplex Virus DNA Encapsidation

2008 ◽  
Vol 83 (1) ◽  
pp. 47-57 ◽  
Author(s):  
Shelley K. Cockrell ◽  
Minerva E. Sanchez ◽  
Angela Erazo ◽  
Fred L. Homa
Keyword(s):  
Amino Acids ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Dna Cleavage ◽  
Virus Protein ◽  
Viral Dna ◽  
Reading Frame ◽  
Viral Genomes ◽  
Simplex Virus

ABSTRACT The herpes simplex virus protein UL25 attaches to the external vertices of herpes simplex virus type 1 capsids and is required for the stable packaging of viral DNA. To define regions of the protein important for viral replication and capsid attachment, the 580-amino-acid UL25 open reading frame was disrupted by transposon mutagenesis. The UL25 mutants were assayed for complementation of a UL25 deletion virus, and in vitro-synthesized protein was tested for binding to UL25-deficient capsids. Of the 11 mutants analyzed, 4 did not complement growth of the UL25 deletion mutant, and analysis of these and additional mutants in the capsid-binding assay demonstrated that UL25 amino acids 1 to 50 were sufficient for capsid binding. Several UL25 mutations were transferred into recombinant viruses to analyze the effect of the mutations on UL25 capsid binding and on DNA cleavage and packaging. Studies of these mutants demonstrated that amino acids 1 to 50 of UL25 are essential for its stable interaction with capsids and that the C terminus is essential for DNA packaging and the production of infectious virus through its interactions with other viral packaging or tegument proteins. Analysis of viral DNA cleavage demonstrated that in the absence of a functional UL25 protein, aberrant cleavage takes place at the unique short end of the viral genome, resulting in truncated viral genomes that are not retained in capsids. Based on these observations, we propose a model where UL25 is required for the formation of DNA-containing capsids by acting to stabilize capsids that contain full-length viral genomes.

scholarly journals Beta interferon and gamma interferon synergize to block viral DNA and virion synthesis in herpes simplex virus-infected cells

2005 ◽  
Vol 86 (9) ◽  
pp. 2421-2432 ◽  
Author(s):  
Amy T. Pierce ◽  
Joanna DeSalvo ◽  
Timothy P. Foster ◽  
Athena Kosinski ◽  
Sandra K. Weller ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Host Immune System ◽  
Viral Dna ◽  
Beta Interferon ◽  
Co Activation ◽  
Infected Cells ◽  
Simplex Virus ◽  
Hsv 1

The capacity of herpes simplex virus type 1 (HSV-1) to replicate in vitro decreases tremendously when animal cell cultures are exposed to ligands of both the alpha/beta interferon (IFN-α/β) receptor and IFN-γ receptor prior to inoculation with low m.o.i.s of HSV-1. However, the available evidence provides no insight into the possible mechanisms by which co-activation of the IFN-α/β- and IFN-γ-signalling pathways produces this effect. Therefore, it has not been possible to differentiate between whether these observations represent an important in vitro model of host immunological suppression of HSV-1 infection or an irrelevant laboratory phenomenon. Therefore, the current study was initiated to determine whether co-activation of the host cell's IFN-α/β and IFN-γ pathways either (i) induced death of HSV-1-infected cells such that virus replication was unable to occur; or (ii) disrupted one or more steps in the process of HSV-1 replication. To this end, multiple steps in HSV-1 infection were compared in populations of Vero cells infected with HSV-1 strain KOS (m.o.i. of 2·5) and exposed to ligands of the IFN-α/β receptor, the IFN-γ receptor or both. The results demonstrated that IFN-β and IFN-γ interact in a synergistic manner to block the efficient synthesis of viral DNA and nucleocapsid formation in HSV-1-infected cells and do so without compromising host-cell viability. It was inferred that IFN-mediated suppression of HSV-1 replication may be a central mechanism by which the host immune system limits the spread of HSV-1 infection in vivo.

scholarly journals Activity and Mechanism of Action of N-Methanocarbathymidine against Herpesvirus and Orthopoxvirus Infections

2006 ◽  
Vol 50 (4) ◽  
pp. 1336-1341 ◽  
Author(s):  
Mark N. Prichard ◽  
Kathy A. Keith ◽  
Debra C. Quenelle ◽  
Earl R. Kern
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Mechanism Of Action ◽  
Type I ◽  
Viral Dna ◽  
Barr Virus ◽  
Epstein Barr ◽  
Simplex Virus

ABSTRACT N-Methanocarbathymidine [(N)-MCT] is a conformationally locked nucleoside analog that is active against some herpesviruses and orthopoxviruses in vitro. The antiviral activity of this molecule is dependent on the type I thymidine kinase (TK) in herpes simplex virus and also appears to be dependent on the type II TK expressed by cowpox and vaccinia viruses, suggesting that it is a substrate for both of these divergent forms of the enzyme. The drug is also a good inhibitor of viral DNA synthesis in both viruses and is consistent with inhibition of the viral DNA polymerase once it is activated by the viral TK homologs. This mechanism of action explains the rather unusual spectrum of activity, which is limited to orthopoxviruses, alphaherpesviruses, and Epstein-Barr virus, since these viruses express molecules with TK activity that can phosphorylate and thus activate the drug. The compound is also effective in vivo and reduces the mortality of mice infected with orthopoxviruses, as well as those infected with herpes simplex virus type 1 when treatment is initiated 24 h after infection. These results indicate that (N)-MCT is active in vitro and in vivo, and its mechanism of action suggests that the molecule may be an effective therapeutic for orthopoxvirus and herpesvirus infections, thus warranting further development.

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