Richard L Thompson , PhD

Herpes simplex virus type-1 HSV-1 is an increasingly important healthproblem and is responsible for the majority of cases of fatal sporaticviral encephalitis and infectious blindness in the United States. Approximately 80 of the adult US population is infected with HSV-I. The virus persists in a latent state in sensory neurons for the life ofthe host and periodically reactivates to cause frank disease. Due tothe lack of an appropriate model system the molecular mechanismscontrolling this important process are currently not known. One of themost common inducers of HSV reactivation in man is fever hyperthermia. A new mouse model of induced HSV reactivation in vivo has been developedutilizing a hyperthermia based induction protocol which is simpleimmersion in warm water, rapid 10 minutes, and effective >90 reactivation rate. This model has demonstrated unequivicably that theganglionic neuron is the reactivating cell as well as the site of infec- tious virus production. Furthermore, the fact that infectious virus canbe recovered from ganglia as soon as 14 hours post treatment, the timerequired for one round of acute virus replication in culture indicatesthat the switch from latent to active viral gene transcription in thesecells occurs very rapidly followingthermal treatment. This closetemporal link between thermal treatment and in vivo reactivation makesthis model the first practical system in which to dissect theinduction-reactivation pathway of HSV in vivo. A panel of virusesincluding wild type strains, mutants, specifically engineeredpromoter-reporter viruses, and a virally packaged vector system for invivo promoter studies, will be employed in this system to: 1 identifythe first transcripts produced upon initiation of reactivation; 2define the promoterelements of these 'Immediate Early Reactivation' genes required specifically for the initiation of transcriptionalchanges; and 3 characterize the roles of these and other relevantviral gene products in establishment, maintenance, and reactivation fromlatency. These studies will result in significant contributions to ourunderstanding of the molecular mechanisms underlying HSV latency andreactivation, and may lead to new strategies for treatment andprevention of HSV infection.

Grant: #R01-EY-013168 Investigators:Thompson, Richard 09-01-2003 -04-30-2008 National Eye Institute Ocular Herpes Simplex Virus (HSV) Infection-Latency and Pathogenesis Role:PI $1,644,933.00 Closed Level:Federal

Grant: #5-R01-AI-32121-14-A0-S0-E0 Investigators:Thompson, Richard 02-01-2003 -01-31-2008 National Institute of Allergy and Infectious Diseases Molecular Analysis of Herpes Simplex Virus-1 Reactivation from Latency Role:PI $426,708.00 Closed Level:Federal

Grant: #5-R01-EY-13168-03-A0-S0-E0 Investigators:Thompson, Richard 09-30-2000 -08-31-2003 National Eye Institute Ocular Herpes Simplex Virus (HSV) Infection-Latency and Pathogenesis Role:PI $1,078,233.00 Closed Level:Federal

Grant: #5-R01-AI-32121-10-A0-S0-E0 Investigators:Thompson, Richard 01-01-1998 -12-31-2002 National Institute of Allergy and Infectious Diseases Molecular Analysis of HSV-1 Reactivation from Latency Role:PI $322,163.00 Closed Level:Federal

Grant: #R01 EY0131688 Investigators:Thompson, Richard 05-01-2008 -04-30-2013 National Eye Institute Ocular HSV Infection-Latency and Pathogenesis Role:PI $1,642,953.00 Active Level:Federal

Grant: #106676 / RC1 AI087336 Investigators:Thompson, Richard 09-26-2009 -08-31-2011 National Institute of Allergy and Infectious Diseases Forward Genetic Analysis of Herpes Simples Virus Ocular Disease Role:PI $309,056.00 Closed Level:Federal

Grant: #Koch1 Investigators:Koch, Diana; Thompson, Richard 06-15-2011 -10-31-2011 Prevent Blindness Ohio A Forward Genetics Approach to Elucidating Novel Gene Involvement in Herpetic Ocular Disease Role:Collaborator $5,000.00 Closed Level:Private Non-Profit

Grant: #110491 \ R01SI093614 Investigators:Thompson, Richard 07-01-2012 -06-30-2017 National Institute of Allergy and Infectious Diseases HSV Latency and Reactivation and the Novel Neuronal Regulation of VP16 in Vivo Role:PI $150,717.00 Active Level:Federal

Grant: #CCHMC 131050 sub NASA NNX13A047G Investigators:Thompson, Richard 01-01-2014 -12-31-2016 National Aeronautics and Space Administration Acute and Long Term Outcomes of Simulated Deep Space Radiation Exposure on Latent Role:PI $27,724.00 Awarded Level:Federal

Grant: #1 R21 AI116389 Investigators:Sawtell, Nancy; Thompson, Richard 01-01-2015 -12-31-2016 National Institute of Allergy and Infectious Diseases Revealing networks targeted by HSV-1 ncRNAs with in vivo gain-of-function studies Role:PI $250,289.00 Awarded Level:Federal

Grant: #CHMC 138459 sub R01AI93614 Investigators:Thompson, Richard 07-01-2016 -06-30-2017 National Institute of Allergy and Infectious Diseases HSV Latency and Reactivation and the Novel Neuronal Regulation of VP16 in Vivo Role:PI $138,761.00 Awarded Level:Federal

Grant: #5845-UC-DHHS-2692 / R01 AI132692 Investigators:Thompson, Richard 02-23-2018 -01-31-2023 National Institute of Allergy and Infectious Diseases Forward genetic prediction and testing of virulence loci in herpes simplex virus 1 Role:PI $29,371.00 Active Level:Federal

Grant: #Research Collaboration Agreement Investigators:Cong, Xinyu; Thompson, Richard 03-01-2019 -02-29-2020 Cincinnati Children's Hospital Medical Center HSV-1 and Alzheimer’s disease project Role:PI $12,892.00 Active Level:Private Non-Profit

Grant: #2021 Microbial Pathogenesis in Alzheimer's Disease Grant Investigators:Thompson, Richard 01-24-2022 -12-24-2022 Infectious Diseases Society of America The intersection of herpes simplex virus infection, the human ApoE4 allele and Alzheimer's disease Role:PI 100000.00 Awarded Level:Non Profit

Grant: #Service Agreement / Investigators:Thompson, Richard 12-16-2022 -12-15-2027 Good Ventures Foundation Production of Alzheimer's -like symptoms by Herpes 1 infections in mice Role:PI 0.00 Hold Level:Non Profit

Grant: #CUMC (R01AG083963) Investigators:Sawtell, Nancy; Thompson, Richard 08-15-2023 -04-30-2028 Columbia University Investigating the role of long-term latent herpes simplex virus infection on ApoE4 - associated Alzheimer's disease pathogenesis Role:Collaborator 22612.00 Hold Level:Higher Education

Peer Reviewed Publications

Sawtell, Nancy M; Thompson, Richard L (2014. ) Herpes simplex virus mutant generation and dual-detection methods for gaining insight into latent/lytic cycles in vivo.Methods in molecular biology (Clifton, N.J.), , 1144 ,129-47 More Information

Thompson, Richard L; Williams, Robert W; Kotb, Malak; Sawtell, Nancy M (2014. ) A forward phenotypically driven unbiased genetic analysis of host genes that moderate herpes simplex virus virulence and stromal keratitis in mice.PloS one, , 9 (3 ) ,e92342 More Information

Thompson, Richard L; Sawtell, Nancy M (2011. ) The herpes simplex virus type 1 latency associated transcript locus is required for the maintenance of reactivation competent latent infections.Journal of neurovirology, , 17 (6 ) ,552-8 More Information

Sawtell, Nancy M; Triezenberg, Steven J; Thompson, Richard L (2011. ) VP16 serine 375 is a critical determinant of herpes simplex virus exit from latency in vivo.Journal of neurovirology, , 17 (6 ) ,546-51 More Information

Thompson, Richard L; Sawtell, Nancy M (2010. ) Therapeutic implications of new insights into the critical role of VP16 in initiating the earliest stages of HSV reactivation from latency.Future medicinal chemistry, , 2 (7 ) ,1099-105 More Information

Thompson, Richard L; Preston, Chris M; Sawtell, Nancy M (2009. ) De novo synthesis of VP16 coordinates the exit from HSV latency in vivo.PLoS pathogens, , 5 (3 ) ,e1000352 More Information

Thompson, R L; Sawtell, N M (2006. ) Evidence that the herpes simplex virus type 1 ICP0 protein does not initiate reactivation from latency in vivo.Journal of virology, , 80 (22 ) ,10919-30 More Information

Sawtell, N M; Thompson, R L; Haas, R L (2006. ) Herpes simplex virus DNA synthesis is not a decisive regulatory event in the initiation of lytic viral protein expression in neurons in vivo during primary infection or reactivation from latency.Journal of virology, , 80 (1 ) ,38-50 More Information

Sawtell, N M; Thompson, R L (2004. ) Comparison of herpes simplex virus reactivation in ganglia in vivo and in explants demonstrates quantitative and qualitative differences.Journal of virology, , 78 (14 ) ,7784-94 More Information

Thompson, R L; Shieh, May T; Sawtell, N M (2003. ) Analysis of herpes simplex virus ICP0 promoter function in sensory neurons during acute infection, establishment of latency, and reactivation in vivo. Journal of virology, , 77 (22 ) ,12319-30

Sawtell, N M; Thompson, R L; Stanberry, L R; Bernstein, D I (2001. ) Early intervention with high-dose acyclovir treatment during primary herpes simplex virus infection reduces latency and subsequent reactivation in the nervous system in vivo.The Journal of infectious diseases, , 184 (8 ) ,964-71 More Information

Thompson, R L; Sawtell, N M (2001. ) Herpes simplex virus type 1 latency-associated transcript gene promotes neuronal survival.Journal of virology, , 75 (14 ) ,6660-75 More Information

Thompson, R L; Sawtell, N M (2000. ) HSV latency-associated transcript and neuronal apoptosis. Science (New York, N.Y.), , 289 (5485 ) ,1651

Thompson, R L; Sawtell, N M (2000. ) Replication of herpes simplex virus type 1 within trigeminal ganglia is required for high frequency but not high viral genome copy number latency. Journal of virology, , 74 (2 ) ,965-74

Sawtell, N M; Poon, D K; Tansky, C S; Thompson, R L (1998. ) The latent herpes simplex virus type 1 genome copy number in individual neurons is virus strain specific and correlates with reactivation. Journal of virology, , 72 (7 ) ,5343-50

Thompson, R L; Sawtell, N M (1997. ) The herpes simplex virus type 1 latency-associated transcript gene regulates the establishment of latency. Journal of virology, , 71 (7 ) ,5432-40

Perng, G C; Chokephaibulkit, K; Thompson, R L; Sawtell, N M; Slanina, S M; Ghiasi, H; Nesburn, A B; Wechsler, S L (1996. ) The region of the herpes simplex virus type 1 LAT gene that is colinear with the ICP34.5 gene is not involved in spontaneous reactivation. Journal of virology, , 70 (1 ) ,282-91

Perng, G C; Thompson, R L; Sawtell, N M; Taylor, W E; Slanina, S M; Ghiasi, H; Kaiwar, R; Nesburn, A B; Wechsler, S L (1995. ) An avirulent ICP34.5 deletion mutant of herpes simplex virus type 1 is capable of in vivo spontaneous reactivation. Journal of virology, , 69 (5 ) ,3033-41

Pyles, R B; Thompson, R L (1994. ) Evidence that the herpes simplex virus type 1 uracil DNA glycosylase is required for efficient viral replication and latency in the murine nervous system. Journal of virology, , 68 (8 ) ,4963-72

Bolovan, C A; Sawtell, N M; Thompson, R L (1994. ) ICP34.5 mutants of herpes simplex virus type 1 strain 17syn+ are attenuated for neurovirulence in mice and for replication in confluent primary mouse embryo cell cultures. Journal of virology, , 68 (1 ) ,48-55

Pyles, R B; Sawtell, N M; Thompson, R L (1992. ) Herpes simplex virus type 1 dUTPase mutants are attenuated for neurovirulence, neuroinvasiveness, and reactivation from latency. Journal of virology, , 66 (11 ) ,6706-13

Sawtell, N M; Thompson, R L (1992. ) Herpes simplex virus type 1 latency-associated transcription unit promotes anatomical site-dependent establishment and reactivation from latency. Journal of virology, , 66 (4 ) ,2157-69

Sawtell, N M; Thompson, R L (1992. ) Rapid in vivo reactivation of herpes simplex virus in latently infected murine ganglionic neurons after transient hyperthermia. Journal of virology, , 66 (4 ) ,2150-6

Thompson, R L; Rogers, S K; Zerhusen, M A (1989. ) Herpes simplex virus neurovirulence and productive infection of neural cells is associated with a function which maps between 0.82 and 0.832 map units on the HSV genome. Virology, , 172 (2 ) ,435-50

Thompson, R L; Devi-Rao, G V; Wagner, E K (1988. ) DNA sequence and RNA transcription through a site of recombination in a non-neurovirulent herpes simplex virus intertypic recombinant. Virus genes, , 1 (3 ) ,275-86

Thompson, R L; Wagner, E K (1988. ) Partial rescue of herpes simplex virus neurovirulence with a 3.2 kb cloned DNA fragment. Virus genes, , 1 (3 ) ,261-73

Cook, M L; Thompson, R L; Stevens, J G (1986. ) A herpes simplex virus mutant is temperature sensitive for reactivation from the latent state: evidence for selective restriction in neuronal cells. Virology, , 155 (1 ) ,293-6

Thompson, R L; Nakashizuka, M; Stevens, J G (1986. ) Vaccine potential of a live avirulent herpes simplex virus. Microbial pathogenesis, , 1 (4 ) ,409-16

Thompson, R L; Cook, M L; Devi-Rao, G B; Wagner, E K; Stevens, J G (1986. ) Functional and molecular analyses of the avirulent wild-type herpes simplex virus type 1 strain KOS. Journal of virology, , 58 (1 ) ,203-11

Draper, K G; Devi-Rao, G; Costa, R H; Blair, E D; Thompson, R L; Wagner, E K (1986. ) Characterization of the genes encoding herpes simplex virus type 1 and type 2 alkaline exonucleases and overlapping proteins. Journal of virology, , 57 (3 ) ,1023-36

Costa, R H; Draper, K G; Devi-Rao, G; Thompson, R L; Wagner, E K (1985. ) Virus-induced modification of the host cell is required for expression of the bacterial chloramphenicol acetyltransferase gene controlled by a late herpes simplex virus promoter (VP5). Journal of virology, , 56 (1 ) ,19-30

Thompson, R L; Devi-Rao, G V; Stevens, J G; Wagner, E K (1985. ) Rescue of a herpes simplex virus type 1 neurovirulence function with a cloned DNA fragment. Journal of virology, , 55 (2 ) ,504-8

Thompson, R L; Wagner, E K; Stevens, J G (1983. ) Physical location of a herpes simplex virus type-1 gene function(s) specifically associated with a 10 million-fold increase in HSV neurovirulence. Virology, , 131 (1 ) ,180-92

Thompson, R L; Stevens, J G (1983. ) Biological characterization of a herpes simplex virus intertypic recombinant which is completely and specifically non-neurovirulent. Virology, , 131 (1 ) ,171-9

Thompson, R L; Stevens, J G (1983. ) Replication at body temperature selects a neurovirulent herpes simplex virus type 2. Infection and immunity, , 41 (2 ) ,855-7

Sawtell, Nancy M; Thompson, Richard L (2016. ) De Novo Herpes Simplex Virus VP16 Expression Gates a Dynamic Programmatic Transition and Sets the Latent/Lytic Balance during Acute Infection in Trigeminal Ganglia.PLoS pathogens, , 12 (9 ) ,e1005877 More Information

Sawtell, Nancy M; Thompson, Richard L (2016. ) Herpes simplex virus and the lexicon of latency and reactivation: a call for defining terms and building an integrated collective framework.F1000Research, , 5 , More Information

Mutant,Neuron,Ganglion,Disease Model,Virus Genetics,Dna Replication,Laboratory Mouse,Complementary Dna,Interfering Virus,Virus Replication,Molecular Genetics,Transfection Vector,Herpes Simplex Virus,Genetic Transcription,In Situ Hybridization,Latent Virus Infection,Genetic Promoter Element,Model Design Development,Polymerase Chain Reaction,Site Directed Mutagenesis,Genetic Regulatory Element

2260 Medical Sciences Building
45267
Phone: 513-558-0063
richard.thompson@uc.edu