Lynda A. Morrison, Ph.D.
Molecular Microbiology and Immunology
Ph.D. in Cellular Biology & Immunology, Washington University - St. Louis, 1988
Herpes simplex virus 1 (HSV-1) is a ubiquitous virus that causes potentially blinding eye disease as well as the common cold sore. HSV-2 is sexually transmitted and affects nearly one fifth of the U.S. population. HSV-2 causes recurrent genital sores and severely affects children acquiring infection from their mothers during birth. Infection with HSV-2 also increases the risk of HIV infection. The primary goals of our research are threefold: to develop new antiviral drugs to reduce the severity of HSV infections, to develop a vaccine strain that protects against HSV, and to elucidate mechanisms by which HSV interferes with immune responses to promote its infection.
Our antiviral drug discovery efforts, in collaboration with the Tavis laboratory, focus on compounds that inhibit enzymes with integrase or RNaseH activity, and their chemical relatives. HSV-1 and HSV-2 encode several enzymes that have activities consistent with an integrase or RNaseH. Up to 1 million-fold suppression of HSV replication can be achieved in cultured cells with several of these compounds. They also have a different mechanism of action than current therapies, suggesting they could be useful in combination with existing drugs to fully suppress replication, or for patients who have infections with HSV that resists existing drugs. We are currently identifying and optimizing lead compounds in cell culture and in mouse models of HSV infection.
Our second goal is to elucidate the genetic basis of HSV’s capacity to replicate and spread so effectively within the body, including the nervous system. A collection of viral proteins packed into the tegument layer of the virus particle perform essential functions that regulate viral and host cell processes. Current studies focus on the ICP34.5 tegument protein of HSV-2, which we have shown is produced in a full-length form and several truncated forms during virus infection. This makes HSV-2 ICP34.5 structurally dissimilar to its HSV-1 homolog, and we are investigating whether its functional capacities are also different. We are also taking an unbiased genetic mapping approach to identify viral geneticdeterminants of successful HSV neuroinvasion beyond ICP34.5.
Labs and Facilities
Lab team members include Bindi Patel, Lynda Morrison, Kaelin Bernier, Stella Hoft, Sree Datla and Miguel Minaya.
Mostafa HH, Thompson TW, Konen AJ, Haenchen SD, Hilliard JG, Macdonald SJ, Morrison LA, and Davido DJ. 2018. Herpes Simplex Virus 1 Mutant with Point Mutations in UL39 Is Impaired for Acute Viral Replication in Mice, Establishment of Latency, and Explant-Induced Reactivation. Journal of Virology 2018 Jan 10. pii: JVI.01645-17. PMID: 29321311
Hirsch DR, Schiavone DV, Berkowitz AJ, Morrison LA, Masaoka T, Wilson JA, Lomonosova E, Zhao H, Patel BS, Datla SH, Hoft SG, Majidi SJ, Pal RK, Gallicchio E, Tang L, Tavis JE, Le Grice SFJ, Beutler JA, and Murelli RP. 2017. Synthesis and biological assessment of 3,7-dihydroxytropolones. Organic and Biomolecular Chemistry 2017 Dec 19;16(1):62-69. PMID: 29098212
Minaya MA, Jensen TL, Goll JB, Korom M, Datla SH, Belshe RB, and Morrison LA. 2017. Molecular Evolution of Herpes Simplex Virus 2 Complete Genomes: Comparison between Primary and Recurrent Infections. Journal of Virology 2017 Nov 14;91(23). pii: e00942-17. PMID: 28931680
Edwards TC, Lomonosova E, Patel JA, Li Q, Villa JA, Gupta AK, Morrison LA, Bailly F, Cotelle P, Giannakopoulou E, Zoidis G, and Tavis JE. 2017. Inhibition of hepatitis B virus replication by N-hydroxyisoquinolinediones and related polyoxygenated heterocycles. Antiviral Research 2017 Jul;143:205-217. PMID: 28450058
Minaya MA, Korom M, Wang H, Belshe RB, and Morrison LA. 2017. The herpevac trial for women: Sequence analysis of glycoproteins from viruses obtained from infected subjects. PLoS One 2017 Apr 27;12(4):e0176687. PMID: 28448558
Ireland PJ, Tavis JE, D'Erasmo MP, Hirsch DR, Murelli RP, Cadiz MM, Patel BS, Gupta AK, Edwards TC, Korom M, Moran EA, and Morrison LA. 2016. Synthetic α-hydroxytropolones inhibit replication of wild-type and acyclovir-resistant herpes simplex viruses. Antimicrobial Agents and Chemotherapy Jan 19. pii: AAC.02675-15. [Epub ahead of print]. PMID: 26787704
Tavis JE, Wang H, Tollefson AE, Ying B, Korom M, Cheng X, Cao F, Davis KL, Wold WSM, and Morrison LA. 2014. Inhibitors of nucleotidyl transferase superfamily enzymes suppress herpes simplex virus replication. Antimicrobial Agents and Chemotherapy Sep 29. pii: AAC.03875-14. PMID: 25267681
Davis KL, Korom M, and Morrison LA. 2014. Herpes simplex virus 2 ICP34.5 confers neurovirulence by regulating the type I interferon response. Virology Sep 15;468-470C:330-339. doi: 10.1016/j.virol.2014.08.015. PMID: 25238641
Korom M, Davis KL, and Morrison LA. 2014. Up to four distinct polypeptides are produced from the γ34.5 open reading frame of herpes simplex virus 2. Journal of Virology 88:11284-11296. PMID: 25031346
Korom M, Wylie KM, Wang H, Davis KL, Sangabathula MS, DeLassus GS, and LA Morrison. 2013. A pro-autophagic antiviral role for the cellular prion protein identified by infection with a herpes simplex virus 1 ICP34.5 mutant. Journal of Virology 87:5882-94.
Wang H, Davido DJ, and Morrison LA. 2013. HSV-1 strain McKrae is more neuroinvasive than HSV-1 KOS after corneal or vaginal inoculation in mice. Virus Research 173:436-440.
Macdonald SJ, Mostafa HH, Morrison LA, and Davido DJ. 2012. Genome sequence of herpes simplex virus 1 strain KOS. Journal of Virology 86:6371-6372.
Macdonald SJ, Mostafa HH, Morrison LA, and Davido DJ. 2012. Genome sequence of herpes simplex virus 1 strain McKrae. Journal of Virology 86:9540-9541.
Mbong EF, Woodley L, Dunkerley E, SchrimpfJS, Morrison LA and Duffy C. 2012. Deletion of the HSV-1 UL49 gene results in mRNA and protein translation defects that are complemented by secondary mutations in UL41. Journal of Virology 86:12351-61.
Schrimpf JE, Tu EM, Wang H, Wong YM, and Morrison LA. 2011. B7 costimulation molecules encoded by replication-defective, vhs-deficient HSV-1 improve
vaccine-induced protection against corneal disease. PLoS ONE 2011 6(8) e22772.
Morrison LA and DeLassus GS. 2011. Breach of the nuclear lamina during assembly of herpes simplex viruses. Nucleus 2 (4):1-6.
Cano-Monreal GL, Wylie KM, Cao F, Tavis JE, Morrison LA. Herpes simplex virus 2 UL13 protein kinase disrupts nuclear lamins. Virology 2009 392(1):137-47.
"Virus-expressing host costimulation molecules" Lynda A. Morrison, no. US 8,257,712 issued 9/4/12
"Frequency and pattern of resistance mutations to novel inhibitors of HSV-1"
07/01/2015 - 06/30/2018
"Dissecting the contribution of viral genetic variation to HSV-1 neuropathogenesis"
05/01/2016 - 04/30/2019
STTR (Casterbridge Pharmaceuticals, Inc.)
"Hit-to-Lead Optimization of Small Molecule Inhibitor of Herpes Simplex Viruses"
08/02/2017 - 07/31/2018
Role: Subaward PI
"Nucleotidyl transferase antagonists as inhibitors of HSV replication"
12/13/2017 - 11/30/2019
STTR (Casterbridge Pharmaceuticals, Inc.)
"Developing novel combination therapies for HSV genital infection"
03/01/2018 – 02/28/2019
Role: Subaward PI