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Lynda A. Morrison, Ph.D.

 

Lynda A. Morrison, Ph.D.
Professor
Molecular Microbiology & Immunology
Saint Louis University School of Medicine


Education:
Ph.D., Washington University, 1988

Doisy Research Center
1100 South Grand Blvd
Office/Lab 607/657
Saint Louis, MO 63104

Email:morrisla@slu.edu
Office: 977-8874
Lab: 977-8873


Lynda A. Morrison, Ph.D.

Research Summary:

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.

To develop a vaccine, we utilize virus strains containing an engineered mutation in a gene essential for virus replication. These viruses express numerous proteins in infected cells but do not reproduce and spread, making them relatively immunogenic and safe. We are using molecular genetic techniques and our knowledge of viral genetics underlying pathogenesis to improve immune responses to the replication-defective prototype vaccine. Thus, we mutate genes that encode viral proteins involved in immune evasion, and insert host molecules into the virus genome that stimulate immune responses. Mice immunized with replication-defective mutants of HSV-1 or HSV-2 develop a long-lived immune response that protects them against disease upon ocular or genital infection, respectively.

A collection of viral proteins packed into the tegument layer of the virus particle perform essential functions that regulate viral and host cell processes. We are studying several of these proteins to understand in greater depth their roles in HSV-2 infection. 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.

Lab Members:

L to R: Sri Chiravuri, Lynda Morrison, Greg Delassus, Hong Wang, Maria Korom, and Katie Davis

Publications

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 Res., 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.

Wylie KM, Schrimpf JE, Morrison LA. Increased eIF2alpha phosphorylation attenuates replication of herpes simplex virus 2 vhs mutants in mouse embryonic fibroblasts and correlates with reduced accumulation of the PKR antagonist ICP34.5. J Virol. 2009 83(18):9151-62.

Vagvala SP, Thebeau LG, Wilson SR, Morrison LA. Virus-encoded b7-2 costimulation molecules enhance the protective capacity of a replication-defective herpes simplex virus type 2 vaccine in immunocompetent mice. J Virol. 2009 83(2):953-60.

 Patents
 “Virus-expressing host costimulation molecules” Lynda A. Morrison, no. US 8,257,712 issued 9/4/12.