Mapping herpes simplex virus type 1 latency-associated transcript sequences that protect from apoptosis mediated by a
1Department of Veterinary and Biomedical Sciences, Nebraska Center for Virology, University of Nebraska, Lincoln 68583-0905, USA.
Journal of Neurovirology
|September 17, 2004
Summary
Latency-associated transcript (LAT) from herpes simplex virus type 1 (HSV-1) prevents apoptosis by inhibiting caspase-8. This function is crucial for HSV-1
Area of Science:
- Virology
- Molecular Biology
- Immunology
Background:
- Herpes simplex virus type 1 (HSV-1) establishes neuronal latency.
- The latency-associated transcript (LAT) is highly expressed during latency and linked to HSV-1 reactivation.
- LAT's anti-apoptotic properties are associated with its role in reactivation.
Purpose of the Study:
- To investigate the specific LAT sequences responsible for inhibiting apoptosis.
- To determine the correlation between LAT's anti-apoptotic function and HSV-1 reactivation phenotype.
Main Methods:
- Analysis of LAT nucleotide fragments (1-1499) for apoptosis inhibition.
- Assessing inhibition of caspase-8 (death receptor pathway) and caspase-9 (mitochondrial pathway) induced apoptosis.
- Correlating LAT fragment function with HSV-1 reactivation phenotype in mutant viruses.
Main Results:
- LAT nucleotides 1-1499 effectively inhibit caspase-8-induced apoptosis.
- This inhibition is specific, as caspase-9-induced apoptosis is not affected.
- The 1.5 kb LAT fragment (nucleotides 1-1499) retains significant anti-apoptotic activity, correlating with high HSV-1 reactivation.
Conclusions:
- The N-terminal portion of LAT (nucleotides 1-1499) is sufficient for inhibiting caspase-8-mediated apoptosis.
- LAT's ability to block the death receptor pathway is critical for the high reactivation phenotype of HSV-1.
- These findings elucidate a key mechanism of HSV-1 latency and reactivation.
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