Publications by authors named "Lawrence T Feldman"

3 Publications

  • Page 1 of 1

The latency-associated transcript of herpes simplex virus type 1 promotes survival and stimulates axonal regeneration in sympathetic and trigeminal neurons.

J Neurovirol 2007 ;13(1):56-66

Department of Pharmacology and Toxicology, University at Buffalo, State University of New York, Buffalo, New York 14214, USA.

Herpes simplex virus type 1 (HSV-1) primarily infects mucoepithelial tissues of the eye, the orofacial region, and to a lesser extent the genitalia. The virus is retrogradely transported through the axons of sensory and sympathetic neurons to their cell bodies to establishe a life-long latent infection. Throughout this latency period, the viral genome is transcriptionally silent except for a single region encoding the latency-associated transcript (LAT). The function of LAT is still largely unknown. To understand how HSV-1 latency might affect neurons, the authors transfected primary cultures of sympathetic neurons and trigeminal sensory neurons obtained from rat embryos with LAT-expressing plasmids. LAT increased the survival of both sympathetic and trigeminal neurons after induction of cell death by nerve growth factor (NGF) deprivation. Because HSV-1 is transported through axons both after initial infection and during reactivation, the authors considered the possibility that LAT may affect axonal growth. They found that LAT expression increased axonal regeneration by twofold in both types of neurons. Inhibition of the mitogen-activated protein kinase (MAPK) pathway reverses stimulation of both neuronal survival and axonal regeneration, which indicates that these effects are mediated through the MAPK pathway. These data provide evidence that HSV-1 LAT promotes survival of sympathetic as well as trigeminal neurons. The authors show for the first time that LAT stimulates axonal regeneration in both sympathetic and trigeminal neurons.
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http://dx.doi.org/10.1080/13550280601156297DOI Listing
July 2007

Problems in the use of herpes simplex virus as a vector.

Int Rev Neurobiol 2003 ;55:99-109

Department of Microbiology, Immunology, and Molecular Genetics, UCLA School of Medicine, Los Angeles, California 90095, USA.

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http://dx.doi.org/10.1016/s0074-7742(03)01003-1DOI Listing
October 2003

Spontaneous molecular reactivation of herpes simplex virus type 1 latency in mice.

Proc Natl Acad Sci U S A 2002 Jan 2;99(2):978-83. Epub 2002 Jan 2.

Department of Microbiology and Immunology, University of California Medical Center, Los Angeles, CA 90024, USA.

Infection of the mouse trigeminal ganglia (TG) is the most commonly used model for the study of herpes simplex virus type 1 (HSV-1) latency. Its popularity is caused, at least in part, by the perception that latent infection can be studied in this system in the absence of spontaneous viral reactivation. However, this perception has never been rigorously tested. To carefully study this issue, the eyes of Swiss-Webster mice were inoculated with HSV-1 (KOS), and 37-47 days later the TG were dissected, serial-sectioned, and probed for HSV-1 ICP4, thymidine kinase, glycoprotein C, and latency-associated transcript RNA by in situ hybridization. Serial sections of additional latently infected TG were probed with HSV-1-specific polyclonal antisera. Analysis of thousands of probed sections revealed abundant expression of viral transcripts, viral protein, and viral DNA replication in about 1 neuron per 10 TG tested. These same neurons were surrounded by a focal white cell infiltrate, indicating the presence of an antigenic stimulus. We conclude that productive cycle viral genes are abundantly expressed in rare neurons of latently infected murine TG and that these events are promptly recognized by an active local immune response. In the absence of detectable infectious virus in these ganglia, we propose the term "spontaneous molecular reactivation" to describe this ongoing process.
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http://dx.doi.org/10.1073/pnas.022301899DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC117416PMC
January 2002