Herpes Virus Replication

Boehmer, Paul E.; Nimonkar, Amitabh V.

doi:10.1080/1521654031000070645

Cited by 97 publications

(82 citation statements)

References 92 publications

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confidence: 99%

“…HSV-1 switches between lytic replication in epithelial cells and a state of latency in sensory neurons during which there is no detectable DNA replication (1). Replication of the genome is mediated by seven essential virus-encoded factors with the following functions: a DNA polymerase (Pol) catalytic subunit (UL30), its associated processivity factor (UL42), a ssDNA binding protein (UL29), a heterotrimeric helicase-primase (UL5, UL8, and UL52) and an initiator protein (UL9) that binds to and unwinds the viral replication origins (1)(2)(3)(4). HSV-1 also encodes several other enzymes that are dispensable for replication in cell culture, which are involved in nucleotide metabolism and perform other important roles in maintaining the viral genome including a thymidine kinase (UL23), a ribonucleotide reductase (UL39 and UL40), a dUTPase (UL50), an exonuclease (UL12), and notably a uracil DNA glycosylase (UDG) (UL2) (4).…”

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“…base excision repair ͉ abasic DNA ͉ uracil DNA glycosylase H erpes simplex virus 1 (HSV-1) is a dsDNA virus with a genome of Ϸ152 kbp (1). HSV-1 switches between lytic replication in epithelial cells and a state of latency in sensory neurons during which there is no detectable DNA replication (1).…”

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The replicative DNA polymerase of herpes simplex virus 1 exhibits apurinic/apyrimidinic and 5′-deoxyribose phosphate lyase activities

Bogani

Boehmer

2008

Proc. Natl. Acad. Sci. U.S.A.

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Base excision repair (BER) is essential for maintaining genome stability both to counter the accumulation of unusual bases and to protect from base loss in the DNA. Herpes simplex virus 1 (HSV-1) is a large dsDNA virus that encodes its own DNA replication machinery, including enzymes involved in nucleotide metabolism. We report on a replicative family B and a herpesvirus-encoded DNA Pol that possesses DNA lyase activity. We have discovered that the catalytic subunit of the HSV-1 DNA polymerase (Pol) (UL30) exhibits apurinic/apyrimidinic (AP) and 5 -deoxyribose phosphate (dRP) lyase activities. These activities are integral to BER and lead to DNA cleavage on the 3 side of abasic sites and 5 -dRP residues that remain after cleavage by 5 -AP endonuclease. The UL30-catalyzed reaction occurs independently of divalent cation and proceeds via a Schiff base intermediate, indicating that it occurs via a lyase mechanism. Partial proteolysis of the Schiff base shows that the DNA lyase activity resides in the Pol domain of UL30. These observations together with the presence of a virus-encoded uracil DNA glycosylase indicates that HSV-1 has the capacity to perform critical steps in BER. These findings have implications on the role of BER in viral genome maintenance during lytic replication and reactivation from latency.base excision repair ͉ abasic DNA ͉ uracil DNA glycosylase H erpes simplex virus 1 (HSV-1) is a dsDNA virus with a genome of Ϸ152 kbp (1). HSV-1 switches between lytic replication in epithelial cells and a state of latency in sensory neurons during which there is no detectable DNA replication (1). Replication of the genome is mediated by seven essential virus-encoded factors with the following functions: a DNA polymerase (Pol) catalytic subunit (UL30), its associated processivity factor (UL42), a ssDNA binding protein (UL29), a heterotrimeric helicase-primase (UL5, UL8, and UL52) and an initiator protein (UL9) that binds to and unwinds the viral replication origins (1-4). HSV-1 also encodes several other enzymes that are dispensable for replication in cell culture, which are involved in nucleotide metabolism and perform other important roles in maintaining the viral genome including a thymidine kinase (UL23), a ribonucleotide reductase (UL39 and UL40), a dUTPase (UL50), an exonuclease (UL12), and notably a uracil DNA glycosylase (UDG) (UL2) (4).The presence of a virus-encoded UDG suggests that excision of uracil may be important during viral replication. Hence, it has been shown that uracil substitutions in the viral origins of replication alters their recognition by the viral initiator protein (5). Moreover, whereas UL2 may be dispensable for viral replication in fibroblast (6), UL2 mutants exhibit reduced neurovirulence and a decreased frequency of reactivation from latency (7). Thus, UDG action in HSV-1 may be important for viral reactivation after quiescence in neuronal cells during which the genome may accumulate uracil as a result of spontaneous deamination of cytosine. In cytomegalovirus, the viral UDG ...

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The replicative DNA polymerase of herpes simplex virus 1 exhibits apurinic/apyrimidinic and 5′-deoxyribose phosphate lyase activities

Bogani

Boehmer

2008

Proc. Natl. Acad. Sci. U.S.A.

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“…Among Herpes Viridae, the reproduction of herpes simplex virus type 1 (HSV-1) is the most extensively studied system (Boehmer & Nimonkar, 2003;Stow, 2000). In the replication process of the HSV-1, the temporal profile of viral gene expression is well understood.…”

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confidence: 99%

The function of temporally ordered viral gene expression in the intracellular replication of herpes simplex virus type 1 (HSV-1)

Nakabayashi

Sasaki

2009

Journal of Theoretical Biology

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“…Replication of Herpes simplex virus type I (HSV-1) relies on the activation of the viral origins of replication oriS and oriL by the origin-binding protein (OBP) 1 encoded by the UL9 gene (1,2). Events catalyzed by OBP assisted by the single-stranded binding protein, ICP8, lead to the assembly of the prototypical herpes virus replisome consisting of the heterodimeric UL30/42 DNA polymerase, the trimeric UL5/8/52 helicase primase complex, and ICP8.…”

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Functional Properties of the Herpes Simplex Virus Type I Origin-binding Protein Are Controlled by Precise Interactions with the Activated Form of the Origin of DNA Replication

Macao

Olsson

Elias

2004

Journal of Biological Chemistry

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The herpes simplex virus, type I origin-binding protein, OBP, is a superfamily II DNA helicase encoded by the UL9 gene. OBP binds in a sequence-specific and cooperative way to the viral origin of replication oriS. OBP may unwind partially and introduce a hairpin into the double-stranded origin of replication. The formation of the novel conformation referred to as oriS* also requires the single-stranded DNA-binding protein, ICP8, and ATP hydrolysis. OBP forms a stable complex with oriS*. The hairpin in oriS* provides a site for sequencespecific attachment, and a single-stranded region triggers ATP hydrolysis. Here we use Escherichia coli exonuclease I to map the binding of the C-terminal domain of OBP to the hairpin and the helicase domains to the single-stranded tail. The helicase domains cover a stretch of 23 nucleotides of single-stranded DNA. Using streptavidin-coated magnetic beads, we show that OBP may bind two copies of double-stranded DNA (one biotin-labeled and the other one radioactively labeled) but only one copy of oriS*. It is the length of the singlestranded tail that determines the stoichiometry of OBP⅐DNA complexes. OBP interacts with the bases of the single-stranded tail, and ATP hydrolysis is triggered by position-specific interactions between OBP and bases in the single-stranded tail of oriS*.

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Herpes Virus Replication

Cited by 97 publications

References 92 publications

The replicative DNA polymerase of herpes simplex virus 1 exhibits apurinic/apyrimidinic and 5′-deoxyribose phosphate lyase activities

The replicative DNA polymerase of herpes simplex virus 1 exhibits apurinic/apyrimidinic and 5′-deoxyribose phosphate lyase activities

The function of temporally ordered viral gene expression in the intracellular replication of herpes simplex virus type 1 (HSV-1)

Functional Properties of the Herpes Simplex Virus Type I Origin-binding Protein Are Controlled by Precise Interactions with the Activated Form of the Origin of DNA Replication

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