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Towards an understanding of the herpes simplex virus type 1 latency-reactivation cycle.

Perng GC, Jones C - Interdiscip Perspect Infect Dis (2010)

Bottom Line: Periodically, reactivation from latency occurs resulting in virus transmission and recurrent disease.During latency, the latency-associated transcript (LAT) is abundantly expressed.In this review, an update of viral factors that are expressed during latency and their potential roles in regulating the latency-reactivation cycle is discussed.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology and Laboratory Medicine, Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322, USA.

ABSTRACT
Infection by herpes simplex virus type 1 (HSV-1) can cause clinical symptoms in the peripheral and central nervous system. Recurrent ocular shedding can lead to corneal scarring and vision loss making HSV-1 a leading cause of corneal blindness due to an infectious agent. The primary site of HSV-1 latency is sensory neurons within trigeminal ganglia. Periodically, reactivation from latency occurs resulting in virus transmission and recurrent disease. During latency, the latency-associated transcript (LAT) is abundantly expressed. LAT expression is important for the latency-reactivation cycle in animal models, in part, because it inhibits apoptosis, viral gene expression, and productive infection. A novel transcript within LAT coding sequences (AL3) and small nonprotein coding RNAs are also expressed in trigeminal ganglia of latently infected mice. In this review, an update of viral factors that are expressed during latency and their potential roles in regulating the latency-reactivation cycle is discussed.

No MeSH data available.


Related in: MedlinePlus

Location of genes within the HSV-1 repeats. (a)  UL and US denote the unique sequences of the long (L) and short (S) components of the genome.  The boxes depict repeat sequences. (b) Transcription map of the repeat region.  Location and orientation of LAT    [114, 115], ICP0, γ134.5    [116, 117], ORFP [118], L/STs [119] are indicated by solid lines.  Partially mapped transcripts (αX and βX) are denoted by dashed arrows    [120, 121]. (c) The LAT promoter contains numerous cis-acting sites that can be bound by cellular transcription factors.  Binding of ICP4 to the ICP4 binding site in the LAT promoter inhibits promoter activity [107].  In transient transfection assays, the LAT promoter can be divided into a strong promoter (LAP1) and a weaker promoter (LAP2)    [99, 100].  For details of transcripts encoded by LAT, see Figure 3.
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fig2: Location of genes within the HSV-1 repeats. (a) UL and US denote the unique sequences of the long (L) and short (S) components of the genome. The boxes depict repeat sequences. (b) Transcription map of the repeat region. Location and orientation of LAT [114, 115], ICP0, γ134.5 [116, 117], ORFP [118], L/STs [119] are indicated by solid lines. Partially mapped transcripts (αX and βX) are denoted by dashed arrows [120, 121]. (c) The LAT promoter contains numerous cis-acting sites that can be bound by cellular transcription factors. Binding of ICP4 to the ICP4 binding site in the LAT promoter inhibits promoter activity [107]. In transient transfection assays, the LAT promoter can be divided into a strong promoter (LAP1) and a weaker promoter (LAP2) [99, 100]. For details of transcripts encoded by LAT, see Figure 3.

Mentions: In sharp contrast to other HSV-1 promoters, the promoter that directs expression of the latency-associated transcript (LAT) is activated in sensory neurons (see Figure 2 for a schematic of the HSV-1 LAT promoter). Two separate promoter fragments that are upstream of the start site of LAT, latency-associated promoter 1 and 2 (LAP1 and LAP2), can cis-activate a reporter gene in transiently transfected cells [99, 100]. Several studies have demonstrated that sequences spanning the TATA box, LAP1, are critical for directing LAT expression in sensory neurons [99, 101–104]. LAP2 promoter has been proposed to promote expression of the stable 2 Kb LAT expression during productive infection of cultured cells. LAP2 may also play a role in promoting long-term expression of LAT in sensory neurons or may activate expression of novel transcripts during specific stages of infection in sensory neurons. Although the LAT promoter elements have neuronal specificity in transient transfection assays, they can also direct expression of a reporter gene in nonneural cells [105–109]. This may reflect the abundance of cellular transcription factor binding sites within the LAT promoter (Figure 2(c)). Many of these transcription factors are present in nonneural cells and can activate the LAT promoter in transiently transfected cells. For example, the two CRE binding sites in the LAT promoter are functional because cAMP activates the promoter [110, 111]. The CRE motif that is proximal to the TATA box is important for expression in neurons, and its presence has a positive effect on reactivation from latency [111–113]. Furthermore, Sp1, YY1, USF, and CAAT are frequently found in RNA polymerase II promoters that are not neural specific. Neuronal specific factors have been identified that bind to the LAT promoter [111–113]. The finding that the IE protein, ICP4, binds to DNA sequences downstream of the TATA box and represses the LAT promoter is one important reason why LAT is not an abundant transcript during productive infection [107].


Towards an understanding of the herpes simplex virus type 1 latency-reactivation cycle.

Perng GC, Jones C - Interdiscip Perspect Infect Dis (2010)

Location of genes within the HSV-1 repeats. (a)  UL and US denote the unique sequences of the long (L) and short (S) components of the genome.  The boxes depict repeat sequences. (b) Transcription map of the repeat region.  Location and orientation of LAT    [114, 115], ICP0, γ134.5    [116, 117], ORFP [118], L/STs [119] are indicated by solid lines.  Partially mapped transcripts (αX and βX) are denoted by dashed arrows    [120, 121]. (c) The LAT promoter contains numerous cis-acting sites that can be bound by cellular transcription factors.  Binding of ICP4 to the ICP4 binding site in the LAT promoter inhibits promoter activity [107].  In transient transfection assays, the LAT promoter can be divided into a strong promoter (LAP1) and a weaker promoter (LAP2)    [99, 100].  For details of transcripts encoded by LAT, see Figure 3.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2822239&req=5

fig2: Location of genes within the HSV-1 repeats. (a) UL and US denote the unique sequences of the long (L) and short (S) components of the genome. The boxes depict repeat sequences. (b) Transcription map of the repeat region. Location and orientation of LAT [114, 115], ICP0, γ134.5 [116, 117], ORFP [118], L/STs [119] are indicated by solid lines. Partially mapped transcripts (αX and βX) are denoted by dashed arrows [120, 121]. (c) The LAT promoter contains numerous cis-acting sites that can be bound by cellular transcription factors. Binding of ICP4 to the ICP4 binding site in the LAT promoter inhibits promoter activity [107]. In transient transfection assays, the LAT promoter can be divided into a strong promoter (LAP1) and a weaker promoter (LAP2) [99, 100]. For details of transcripts encoded by LAT, see Figure 3.
Mentions: In sharp contrast to other HSV-1 promoters, the promoter that directs expression of the latency-associated transcript (LAT) is activated in sensory neurons (see Figure 2 for a schematic of the HSV-1 LAT promoter). Two separate promoter fragments that are upstream of the start site of LAT, latency-associated promoter 1 and 2 (LAP1 and LAP2), can cis-activate a reporter gene in transiently transfected cells [99, 100]. Several studies have demonstrated that sequences spanning the TATA box, LAP1, are critical for directing LAT expression in sensory neurons [99, 101–104]. LAP2 promoter has been proposed to promote expression of the stable 2 Kb LAT expression during productive infection of cultured cells. LAP2 may also play a role in promoting long-term expression of LAT in sensory neurons or may activate expression of novel transcripts during specific stages of infection in sensory neurons. Although the LAT promoter elements have neuronal specificity in transient transfection assays, they can also direct expression of a reporter gene in nonneural cells [105–109]. This may reflect the abundance of cellular transcription factor binding sites within the LAT promoter (Figure 2(c)). Many of these transcription factors are present in nonneural cells and can activate the LAT promoter in transiently transfected cells. For example, the two CRE binding sites in the LAT promoter are functional because cAMP activates the promoter [110, 111]. The CRE motif that is proximal to the TATA box is important for expression in neurons, and its presence has a positive effect on reactivation from latency [111–113]. Furthermore, Sp1, YY1, USF, and CAAT are frequently found in RNA polymerase II promoters that are not neural specific. Neuronal specific factors have been identified that bind to the LAT promoter [111–113]. The finding that the IE protein, ICP4, binds to DNA sequences downstream of the TATA box and represses the LAT promoter is one important reason why LAT is not an abundant transcript during productive infection [107].

Bottom Line: Periodically, reactivation from latency occurs resulting in virus transmission and recurrent disease.During latency, the latency-associated transcript (LAT) is abundantly expressed.In this review, an update of viral factors that are expressed during latency and their potential roles in regulating the latency-reactivation cycle is discussed.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology and Laboratory Medicine, Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322, USA.

ABSTRACT
Infection by herpes simplex virus type 1 (HSV-1) can cause clinical symptoms in the peripheral and central nervous system. Recurrent ocular shedding can lead to corneal scarring and vision loss making HSV-1 a leading cause of corneal blindness due to an infectious agent. The primary site of HSV-1 latency is sensory neurons within trigeminal ganglia. Periodically, reactivation from latency occurs resulting in virus transmission and recurrent disease. During latency, the latency-associated transcript (LAT) is abundantly expressed. LAT expression is important for the latency-reactivation cycle in animal models, in part, because it inhibits apoptosis, viral gene expression, and productive infection. A novel transcript within LAT coding sequences (AL3) and small nonprotein coding RNAs are also expressed in trigeminal ganglia of latently infected mice. In this review, an update of viral factors that are expressed during latency and their potential roles in regulating the latency-reactivation cycle is discussed.

No MeSH data available.


Related in: MedlinePlus