Guey-chuen Perng
Assistant Professor, Ophthalmology
School of Medicine
School of Medicine
Ph.D., UC Davis, 1990, Microbiology and Molecular Biology
University of California, Irvine
UCIMC, Bldg. 55, Rm. 204
Mail Code: 4380
Irvine, CA 92697
UCIMC, Bldg. 55, Rm. 204
Mail Code: 4380
Irvine, CA 92697
Research Interests
Virus-host interactions involved in Herpes simplex encephalitis and latency-reactivation pathogenesis
Research Abstract
Pathogenesis—virus host factors interactions
To elucidate the complex interactions between HSV-1 and a susceptible host and to understand the pathogenesis of HSV-1 infections and the host response to these infections are highly challenging tasks. HSV-1 can cause encephalitis in infected animals and humans. Although herpes encephalitis is rare in adults, it affects 2-5% of infected infants and is therefore of significant clinical importance. Overall, there are around 2,000 report cases each year in the United States. We have shown that LAT is involved in neurovirulence in experimentally infected animals. Deletion of different portions of the LAT gene can alter the rate of death due to encephalitis. The regulation of virulence in HSV-1 infected animals is very complicated as the outcome with some of the mutants varies in mice compared to rabbits. My interest is deciphering the up and down regulation of cytokines or virus-host interactions involved in immune cells in HSV 1 infected brains, as this directly affects viral load in the brain and therefore is an important factors in the pathogenesis of herpes encephalitis. One specific focus will be understanding the molecular biology of how LAT or UOL contributes to this cytokine regulation and/or evade immune cells clearance during infection.
Cell Biology and molecular virology
HSV-1 is a very intricate DNA virus. It can establish latency in its host and reactivate from latency. Consequently, the latency-reactivation cycle can promote corneal disease leading to blindness, and encephalitis. We have shown that the LAT gene---the only HSV-1 gene actively transcribed during neuronal latency---is an essential element responsible for reactivation, mapped this essential factor within a small region of the LAT gene, have recently demonstrated that this small fragment can block viral induced neuronal program cell death, and have co-mapped LAT’s antiapoptosis activity to the region that is required for high levels of spontaneous reactivation.
Specific protein-protein interactions are central to most biological processes, ranging from basic cellular functions, such as DNA replication, gene transcription, and protein synthesis, to more specialized processes involved in cell-cell signaling and immune responses. Comprehending the functions of proteins is key to understanding how complex biological systems execute in normal physiological situations and for understanding how these systems are dysregulated in pathological conditions. Clues to the function of an unknown protein can be obtained by investigating its interaction with other proteins whose functions are already known. Proteins that directly interact with each other can be expected to participate in the same cellular processes. On this basis, the finding that a protein of unknown function binds to a protein of known function provides significant information as to the cellular pathway in which the unknown protein participates. This concept has been termed “guilt by association”. Furthermore, this information will often lead to understanding the precise role played by the protein in a complex pathway.
The intricate interactions between the latently infected cell and the latent HSV 1 DNA and how they result in viral reactivation in response to environmental stress is a highly challenging and exciting area of research. The mechanisms involved in the virus—cell interaction and how the virus returns back to the original peripheral site of infection are fascinating. I expect over the next several years to continue teasing apart the mechanisms involved in this system.
Gene Therapy and/or therapeutic agents
During neuronal latency HSV-1 does not cause any detectable clinical pathology. All of the viral genes except for LAT are inactive. I have constructed several HSV 1 vector systems in which a foreign gene can be inserted into the virus under control of the LAT promoter. This results in long term high level expression of the gene in both acutely and latently infected neurons. The HSV 1 vector has also been modified so that it does not damage neurons during the acute infection, allows latency to be established, and does not allow the latent virus to reactivate. Theoretically this is an ideal vector for delivering foreign genes to the CNS. In one version of the system the LAT promoter can be turned on and off by administering or withholding tetracycline. This will be useful if the desired foreign gene needs to be active only during defined periods of time.
RNA interference (RNAi) is a biological process in which the introduction of double-stranded RNA (dsRNA) into a cell results in specific targeted silencing of gene expression. It is a homology-based silencing system. RNAi is remarkably specific and represents an enormous potential technology for developing new therapeutic agents.
HSV-1 infection is a bothersome disease and the virus is associated with its host lifelong. There is no effective vaccine available and no efficient drugs can totally eliminate the virus from the infected host or completely suppress viral recurrence. Acyclovir therapy only reduces disease and duration of recurrent symptoms by approximately 40% and it does not prevent reactivation from latency. The use of RNAi technology to target on LAT, which is required for reactivation, a potential new therapeutic treatment for preventing HSV-1 reactivation from latency can be developed.
To elucidate the complex interactions between HSV-1 and a susceptible host and to understand the pathogenesis of HSV-1 infections and the host response to these infections are highly challenging tasks. HSV-1 can cause encephalitis in infected animals and humans. Although herpes encephalitis is rare in adults, it affects 2-5% of infected infants and is therefore of significant clinical importance. Overall, there are around 2,000 report cases each year in the United States. We have shown that LAT is involved in neurovirulence in experimentally infected animals. Deletion of different portions of the LAT gene can alter the rate of death due to encephalitis. The regulation of virulence in HSV-1 infected animals is very complicated as the outcome with some of the mutants varies in mice compared to rabbits. My interest is deciphering the up and down regulation of cytokines or virus-host interactions involved in immune cells in HSV 1 infected brains, as this directly affects viral load in the brain and therefore is an important factors in the pathogenesis of herpes encephalitis. One specific focus will be understanding the molecular biology of how LAT or UOL contributes to this cytokine regulation and/or evade immune cells clearance during infection.
Cell Biology and molecular virology
HSV-1 is a very intricate DNA virus. It can establish latency in its host and reactivate from latency. Consequently, the latency-reactivation cycle can promote corneal disease leading to blindness, and encephalitis. We have shown that the LAT gene---the only HSV-1 gene actively transcribed during neuronal latency---is an essential element responsible for reactivation, mapped this essential factor within a small region of the LAT gene, have recently demonstrated that this small fragment can block viral induced neuronal program cell death, and have co-mapped LAT’s antiapoptosis activity to the region that is required for high levels of spontaneous reactivation.
Specific protein-protein interactions are central to most biological processes, ranging from basic cellular functions, such as DNA replication, gene transcription, and protein synthesis, to more specialized processes involved in cell-cell signaling and immune responses. Comprehending the functions of proteins is key to understanding how complex biological systems execute in normal physiological situations and for understanding how these systems are dysregulated in pathological conditions. Clues to the function of an unknown protein can be obtained by investigating its interaction with other proteins whose functions are already known. Proteins that directly interact with each other can be expected to participate in the same cellular processes. On this basis, the finding that a protein of unknown function binds to a protein of known function provides significant information as to the cellular pathway in which the unknown protein participates. This concept has been termed “guilt by association”. Furthermore, this information will often lead to understanding the precise role played by the protein in a complex pathway.
The intricate interactions between the latently infected cell and the latent HSV 1 DNA and how they result in viral reactivation in response to environmental stress is a highly challenging and exciting area of research. The mechanisms involved in the virus—cell interaction and how the virus returns back to the original peripheral site of infection are fascinating. I expect over the next several years to continue teasing apart the mechanisms involved in this system.
Gene Therapy and/or therapeutic agents
During neuronal latency HSV-1 does not cause any detectable clinical pathology. All of the viral genes except for LAT are inactive. I have constructed several HSV 1 vector systems in which a foreign gene can be inserted into the virus under control of the LAT promoter. This results in long term high level expression of the gene in both acutely and latently infected neurons. The HSV 1 vector has also been modified so that it does not damage neurons during the acute infection, allows latency to be established, and does not allow the latent virus to reactivate. Theoretically this is an ideal vector for delivering foreign genes to the CNS. In one version of the system the LAT promoter can be turned on and off by administering or withholding tetracycline. This will be useful if the desired foreign gene needs to be active only during defined periods of time.
RNA interference (RNAi) is a biological process in which the introduction of double-stranded RNA (dsRNA) into a cell results in specific targeted silencing of gene expression. It is a homology-based silencing system. RNAi is remarkably specific and represents an enormous potential technology for developing new therapeutic agents.
HSV-1 infection is a bothersome disease and the virus is associated with its host lifelong. There is no effective vaccine available and no efficient drugs can totally eliminate the virus from the infected host or completely suppress viral recurrence. Acyclovir therapy only reduces disease and duration of recurrent symptoms by approximately 40% and it does not prevent reactivation from latency. The use of RNAi technology to target on LAT, which is required for reactivation, a potential new therapeutic treatment for preventing HSV-1 reactivation from latency can be developed.
Publications
1. LeFebvre, R.B. and Perng, G.C. (1989). Genetic and antigenic characterization of Borrelia coriaceae, putative agent of epizootic bovine abortion. J Clin Microbiol. 27:389-93.
2. Anderson, J.F., Magnarelli, L.A., LeFebvre, R.B., Andreadis, T.G., McAninch, J.B., Perng, G.C. and Johnson, R.C. (1989). Antigenically variable Borrelia burgdorferi isolated from cottontail rabbits and Ixodes dentatus in rural and urban areas. J Clin Microbiol. 27:13-20.
3. LeFebvre, R.B., Perng, G.C. and Johnson, R.C. (1989). Characterization of Borrelia burgdorferi isolates by restriction endonuclease analysis and DNA hybridization. J Clin Microbiol. 27:636-9.
4. LeFebvre, R.B., Lane, R.S., Perng, G.C., Brown, J.A. and Johnson, R.C. (1990). DNA and protein analyses of tick-derived isolates of Borrelia burgdorferi from California. J Clin Microbiol. 28:700-7.
5. Lefebvre, R.B., Perng, G.C. and Johnson, R.C. (1990). The 83-kilodalton antigen of Borrelia burgdorferi which stimulates immunoglobulin M (IgM) and IgG responses in infected hosts is expressed by a chromosomal gene. J Clin Microbiol. 28:1673-5.
6. Perng, G.C. and LeFebvre, R.B. (1990). Expression of antigens from chromosomal and linear plasmid DNA of Borrelia coriaceae. Infect Immun. 58:1744-8.
7. Perng, G.C., LeFebvre, R.B. and Johnson, R.C. (1991). Further characterization of a potent immunogen and the chromosomal gene encoding it in the Lyme disease agent, Borrelia burgdorferi. Infect Immun. 59:2070-4.
8. LeFebvre, R.B., Probert, W.S. and Perng, G.C. (1993). Characterization of a chromosomal gene and the antigen it expresses from the Lyme disease agent, Borrelia burgdorferi. J Clin Microbiol. 31:2146-51.
9. Perng, G.C., Dunkel, E.C., Geary, P.A., Slanina, S.M., Ghiasi, H., Kaiwar, R., Nesburn, A.B. and Wechsler, S.L. (1994). The latency-associated transcript gene of herpes simplex virus type 1 (HSV-1) is required for efficient in vivo spontaneous reactivation of HSV-1 from latency. J Virol. 68:8045-55.
10. Perng, G.C., Ghiasi, H., Kaiwar, R., Nesburn, A.B. and Wechsler, S.L. (1994). An improved method for cloning portions of the repeat regions of herpes simplex virus type 1. J Virol Methods. 46:111-6.
11. Perng, G.C., Zwaagstra, J.C., Ghiasi, H., Kaiwar, R., Brown, D.J., Nesburn, A.B. and Wechsler, S.L. (1994). Similarities in regulation of the HSV-1 LAT promoter in corneal and neuronal cells. Invest Ophthalmol Vis Sci. 35:2981-9.
12. Perng, G.C., Thompson, R.L., Sawtell, N.M., Taylor, W.E., Slanina, S.M., Ghiasi, H., Kaiwar, R., Nesburn, A.B. and Wechsler, S.L. (1995). An avirulent ICP34.5 deletion mutant of herpes simplex virus type 1 is capable of in vivo spontaneous reactivation. J Virol. 69:3033-41.
13. Perng, G.C., Ghiasi, H., Slanina, S.M., Nesburn, A.B. and Wechsler, S.L. (1996). High-dose ocular infection with a herpes simplex virus type 1 ICP34.5 deletion mutant produces no corneal disease or neurovirulence yet results in wild-type levels of spontaneous reactivation. J Virol. 70:2883-93.
14. Ghiasi, H., Perng, G.C., Cai, S., Nesburn, A.B. and Wechsler, S.L. (1996). The UL3 open reading frame of herpes simplex virus type 1 codes for a phosphoprotein. Virus Res. 44:137-42.
15. Perng, G.C., Chokephaibulkit, K., Thompson, R.L., Sawtell, N.M., Slanina, S.M., Ghiasi, H., Nesburn, A.B. and 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. J Virol. 70:282-91.
16. Perng, G.C., Ghiasi, H., Slanina, S.M., Nesburn, A.B. and Wechsler, S.L. (1996). The spontaneous reactivation function of the herpes simplex virus type 1 LAT gene resides completely within the first 1.5 kilobases of the 8.3-kilobase primary transcript. J Virol. 70:976-84.
17. Perng, G.C., Slanina, S.M., Ghiasi, H., Nesburn, A.B. and Wechsler, S.L. (1996). A 371-nucleotide region between the herpes simplex virus type 1 (HSV-1) LAT promoter and the 2-kilobase LAT is not essential for efficient spontaneous reactivation of latent HSV-1. J Virol. 70:2014-8.
18. Drolet, B.S., Perng, G.C., Cohen, J., Slanina, S.M., Yukht, A., Nesburn, A.B. and Wechsler, S.L. (1998). The region of the herpes simplex virus type 1 LAT gene involved in spontaneous reactivation does not encode a functional protein. Virology. 242:221-32.
19. Carr, D.J., Halford, W.P., Veress, L.A., Noisakran, S., Perng, G.C. and Wechsler, S.L. (1998). The persistent elevated cytokine mRNA levels in trigeminal ganglia of mice latently infected with HSV-1 are not due to the presence of latency associated transcript (LAT) RNAs. Virus Res. 54:1-8.
20. Loutsch, J.M., Perng, G.C., Hill, J.M., Zheng, X., Marquart, M.E., Block, T.M., Ghiasi, H., Nesburn, A.B. and Wechsler, S.L. (1999). Identical 371-base-pair deletion mutations in the LAT genes of herpes simplex virus type 1 McKrae and 17syn+ result in different in vivo reactivation phenotypes. J Virol. 73:767-71.
21. Drolet, B.S., Perng, G.C., Villosis, R.J., Slanina, S.M., Nesburn, A.B. and Wechsler, S.L. (1999). Expression of the first 811 nucleotides of the herpes simplex virus type 1 latency-associated transcript (LAT) partially restores wild-type spontaneous reactivation to a LAT-null mutant. Virology. 253:96-106.
22. Ghiasi, H., Perng, G.C., Nesburn, A.B. and Wechsler, S.L. (1999). Either a CD4(+)or CD8(+)T cell function is sufficient for clearance of infectious virus from trigeminal ganglia and establishment of herpes simplex virus type 1 latency in mice. Microb Pathog. 27:387-94.
23. Ghiasi, H., Cai, S., Perng, G.C., Nesburn, A.B. and Wechsler, S.L. (1999). Perforin pathway is essential for protection of mice against lethal ocular HSV-1 challenge but not corneal scarring. Virus Res. 65:97-101.
24. Ghiasi, H., Hofman, F.M., Cai, S., Perng, G.C., Nesburn, A.B. and Wechsler, S.L. (1999). Vaccination with different HSV-1 glycoproteins induces different patterns of ocular cytokine responses following HSV-1 challenge of vaccinated mice. Vaccine. 17:2576-82.
25. Ghiasi, H., Cai, S., Slanina, S.M., Perng, G.C., Nesburn, A.B. and Wechsler, S.L. (1999). The role of interleukin (IL)-2 and IL-4 in herpes simplex virus type 1 ocular replication and eye disease. J Infect Dis. 179:1086-93.
26. Ghiasi, H., Perng, G.C., Hofman, F.M., Cai, S., Nesburn, A.B. and Wechsler, S.L. (1999). Specific and nonspecific immune stimulation of MHC-II-deficient mice results in chronic HSV-1 infection of the trigeminal ganglia following ocular challenge. Virology. 258:208-16.
27. Perng, G.C., Slanina, S.M., Yukht, A., Ghiasi, H., Nesburn, A.B. and Wechsler, S.L. (1999). Herpes simplex virus type 1 serum neutralizing antibody titers increase during latency in rabbits latently infected with latency-associated transcript (LAT)-positive but not LAT-negative viruses. J Virol. 73:9669-72.
28. Perng, G.C., Slanina, S.M., Yukht, A., Drolet, B.S., Keleher, W., Jr., Ghiasi, H., Nesburn, A.B. and Wechsler, S.L. (1999). A herpes simplex virus type 1 latency-associated transcript mutant with increased virulence and reduced spontaneous reactivation. J Virol. 73:920-9.
29. Ghiasi, H., Cai, S., Perng, G.C., Nesburn, A.B. and Wechsler, S.L. (2000). Both CD4+ and CD8+ T cells are involved in protection against HSV-1 induced corneal scarring. Br J Ophthalmol. 84:408-12.
30. Perng, G.C., Jones, C., Ciacci-Zanella, J., Stone, M., Henderson, G., Yukht, A., Slanina, S.M., Hofman, F.M., Ghiasi, H., Nesburn, A.B. and Wechsler, S.L. (2000). Virus-induced neuronal apoptosis blocked by the herpes simplex virus latency-associated transcript. Science. 287:1500-3.
31. Perng, G.C., Slanina, S.M., Yukht, A., Ghiasi, H., Nesburn, A.B. and Wechsler, S.L. (2000). The latency-associated transcript gene enhances establishment of herpes simplex virus type 1 latency in rabbits. J Virol. 74:1885-91.
32. Ghiasi, H., Cai, S., Perng, G.C., Nesburn, A.B. and Wechsler, S.L. (2000). The role of natural killer cells in protection of mice against death and corneal scarring following ocular HSV-1 infection. Antiviral Res. 45:33-45.
33. Ghiasi, H., Perng, G.C., Nesburn, A.B. and Wechsler, S.L. (2000). Antibody-dependent enhancement of HSV-1 infection by anti-gK sera. Virus Res. 68:137-44.
34. Inman, M., Perng, G.C., Henderson,G., Ghiasi. H., Nesburn, A.B., Wechsler, S.L., and Jones, C. (2001) Localization of DNA sequences in the latency-associated transcript (LAT) gene of herpes simplex virus type 1 that promote cell survival and spontaneous reactivation. J.Virol. 75(8):3636-46.
35. Ghiasi, H., Hofman, F.M., Wallner, K., Cai, S., Perng, G.C., Nesburn, A.B., and Wechsler, S.L.. (2000). Corneal macrophage infiltrates following ocular herpes simplex virus type 1 challenge vary in BALB/c mice vaccinated with different vaccines. Vaccine 19:1266-73.
36. Perng, G.C., Slanina, S.M., Ghiasi, H., Nesburn, A.B., and Wechsler, S.L.. (2001) The effect of LAT (latency associated transcript) on the herpes simplex virus type 1 (HSV 1) latency-reactivation phenotype is mouse strain dependent. J.g.Virol, 82(Pt 5):1117-22.
37. Samoto, K., Perng, G.C., Ehtesham, M., Liu, Y., Wechsler, S.L., Nesburn, A.B., Black, K.L., and Yu, J.S.. (2001). A herpes simplex virus type 1 mutant deleted for ?34.5 and LAT kills glioma cells in vitro and is inhibited for in vivo reactivation. Cancer Gene Therapy, 8(4):269-77.
38. Perng, G.C., Esmaili, D., Slanina, S.M., Yukht, A., Ghiasi, H., Osorio N., Mott, K.R., Maguen, B., Jin, L., Nesburn, A.B., and Wechsler, S.L.. (2001). Three herpes simplex virus type 1 latency-associated transcript mutants with distinct and asymmetric effects on virulence in mice compared with rabbits. J. Virol.,75(19):9018-9028.
39. Ghiasi, H., Osorio, Y., Perng, G.C., Nesburn, A.B., and Wechsler, S.L..(2001). Recombinant Herpes Simplex Virus Type 1 Expressing Murine Interleukin-4 Is Less Virulent than Wild-Type Virus in Mice. J Virol.,75(19):9029-36.
40. Perng, G.C., Maguen, B., Jin, L., Mott, K.R., Osorio, N., Slanina, S.M., Yukht, A., Ghiasi, H., Nesburn, A.B., Inman, M., Henderson, G., Jones, C., and Wechsler, S.L..(2002). A gene capable of blocking apoptosis can substitute for the herpes simplex virus type 1 latency-associated transcript gene and restore wild-type reactivation levels. J Virol.76(3):1224-35.
41. Samoto, K., Ehtesham, M., Perng, G.C., Hashizume, K., Wechsler, S.L., Nesburn, A.B., Black, K.L., and Yu, J.S.. (2002). A Herpes Simplex Virus Type 1 Mutant with ?34.5 and LAT Deletions Effectively Oncolyses Human U87 Glioblastomas in Nude Mice.Neurosurgery.50(3):599-606.
42. Moxley, M.J., Block, M.T., Liu, H.C., Fraser, N.W., Perng, G.C., Wechsler, S.L., and Su, Y.H.. (2002). Herpes simplex virus type 1 infection prevents detachment of nerve growth factor-differentiated PC12 cells in culture. J. g.Virol, 83, 1591-1600.
43. Osario, Y., Sharifi, B.G., Perng, G.C., Ghiasi, N.S., and Ghiasi, H.. (2002). The role of TH1 and TH2 cytokines in HSV-1 induced corneal scarring. Ocul. Immunol. Inflamm.2002. Jun; 10(2):105-16.
44. Perng, G.C., Maguen, B., Jin, L., Mott, K.R., Benmohamed, L., Yukht, A., Osorio, N., Nesburn, A.B., Henderson, G., Inman, M., Jones, C., and Wechsler, S.L.. (2002). A novel herpes simplex virus type 1 (HSV 1) transcript (AL RNA) antisense to the 5’ end of LAT (latency associated transcript) produces a protein in infected rabbits. J.Virol. 76(16):8003-8010.
45. Ghiasi, H., Osorio, Y., Perng, G.C., Nesburn, A.B., and Wechsler, S.L.. (2002). Overexpression of Interleukin-2 by a Recombinant Herpes Simplex Virus Type 1 Attenuates Pathogenicity and Enhances Antiviral Immunity. J.Virol. 2002. 76(18): 9069-9078.
46. Ghiasi, H., Osorio, Y., Hedvat, Y., Perng, G.C., Nesburn, A.B., and Wechsler, S.L.. (2002). Infection of BALB/c Mice with a Herpes Simplex Virus Type 1 Recombinant Virus Expressing IFN-gamma Driven by the LAT Promoter. Virology (302): 144-154.
47. Perng, G.C., Mott, K.R., Osorio, N., Yukht, A., Salina, S., Nguyen, Q.H. , Nesburn, A.B., and Wechsler, S.L.. (2002). Herpes simplex virus type 1 (HSV 1) mutants containing the KOS HSV 1 strain ICP34.5 gene in place of the HSV 1 McKrae ICP34.5 gene have McKrae-like spontaneous reactivation and non Mckrae-like virulence. J.g. Virol, 83, 2933-2942.
48. Henderson, G., Peng, W., Jin, L., Perng, G.C., Nesburn, A.B., Wechsler, S.L., and Jones, C..(2002). Regulation of caspase 8 and caspase 9 induced apoptosis by the herpes simplex virus type 1 (HSV 1) latency associated transcript (LAT). J Neurovirol. (8) Suppl 2:103-11.
49. Jin, L., Peng, W., Perng, G.C., Brick, D.J., Nesburn, A.B., Jones, C., and Wechsler, S.L.. (2003).Identification of herpes simplex virus type 1 (HSV-1) latency associated transcript (LAT) sequences that both inhibit apoptosis and enhance the spontaneous reactivation phenotype. J. Viol. 2003. 77(11):6556-61.
50. Peng, W., Henderson, G., Perng, G.C., Nesburn, A.B., Wechsler, S.L. and Jones, C. (2003) The herpes simplex virus type 1 (HSV 1) latency associated transcript (LAT) promotes splicing of the Bcl-x transcript to Bcl-xL, which encodes an anti-apoptosis protein, rather than to Bcl-xS which encodes a pro-apoptotic protein. J.Virol. In Press.
51. Mott, K.R., Osorio, N., Jin, L., Brick, D.J., Naito, J., Cooper, J., Henderson, G., Inman, M., Jones, C., Wechsler, S.L., and Perng, G.C. (2003). The BHV-1 LR ORF-2 is critical for this gene’s ability to restore the high wild type reactivation phenotype to an HSV-1 LAT null mutant. J gen Virol.84:2875-2989.
52. Henderson G, Perng GC, Nesburn AB, Wechsler SL, and Jones C (2004). The latency related (LR) gene encoded by bovine herpesvirus (BHV-1) can suppress caspase 3 and Caspase 9 cleavage during productive infection. J. Neurovirol.10(1):64-70.
53. L Jin, GC Perng, DJ Brick, J Naito, AB Nesburn, C Jones, and SL Wechsler. (2004). Methods for detecting the HSV-1 LAT anti-apoptosis activity in virus infected tissue culture cells. Submitted to Journal. Virol. Methods. 118(1):9-13.
54.Drolet B., Mott K.R., Wechsler S.L., Perng, G.C. (2003). Gylcoprotein C of herpes simplex virus type 1 is required to cause corneal disease at low infectious doses in intact cornea. Curent Eye Research. In Press.
55. Barsam CA, Brick DJ, Jones C, Wechsler SL, Perng G.C. (2004). Infection of rabbit eyes ocularly with a high spontaneous reactivation phenotype HSV-1 mutant may provide a good and reproducible mdoel to study the causes of sever corneal scarring. Cornea. In Press.
56. Julie Naito, Ruma Mukerjee, Kevin R. Mott, Wen Kang, Nelson Osorio, Nigel W. Fraser, and Guey-Chuen Perng. (2004). Identification of a protein encoded in the herpes simplex virus type 1 latency associated transcript promoter region. Virus Research. In Press.
2. Anderson, J.F., Magnarelli, L.A., LeFebvre, R.B., Andreadis, T.G., McAninch, J.B., Perng, G.C. and Johnson, R.C. (1989). Antigenically variable Borrelia burgdorferi isolated from cottontail rabbits and Ixodes dentatus in rural and urban areas. J Clin Microbiol. 27:13-20.
3. LeFebvre, R.B., Perng, G.C. and Johnson, R.C. (1989). Characterization of Borrelia burgdorferi isolates by restriction endonuclease analysis and DNA hybridization. J Clin Microbiol. 27:636-9.
4. LeFebvre, R.B., Lane, R.S., Perng, G.C., Brown, J.A. and Johnson, R.C. (1990). DNA and protein analyses of tick-derived isolates of Borrelia burgdorferi from California. J Clin Microbiol. 28:700-7.
5. Lefebvre, R.B., Perng, G.C. and Johnson, R.C. (1990). The 83-kilodalton antigen of Borrelia burgdorferi which stimulates immunoglobulin M (IgM) and IgG responses in infected hosts is expressed by a chromosomal gene. J Clin Microbiol. 28:1673-5.
6. Perng, G.C. and LeFebvre, R.B. (1990). Expression of antigens from chromosomal and linear plasmid DNA of Borrelia coriaceae. Infect Immun. 58:1744-8.
7. Perng, G.C., LeFebvre, R.B. and Johnson, R.C. (1991). Further characterization of a potent immunogen and the chromosomal gene encoding it in the Lyme disease agent, Borrelia burgdorferi. Infect Immun. 59:2070-4.
8. LeFebvre, R.B., Probert, W.S. and Perng, G.C. (1993). Characterization of a chromosomal gene and the antigen it expresses from the Lyme disease agent, Borrelia burgdorferi. J Clin Microbiol. 31:2146-51.
9. Perng, G.C., Dunkel, E.C., Geary, P.A., Slanina, S.M., Ghiasi, H., Kaiwar, R., Nesburn, A.B. and Wechsler, S.L. (1994). The latency-associated transcript gene of herpes simplex virus type 1 (HSV-1) is required for efficient in vivo spontaneous reactivation of HSV-1 from latency. J Virol. 68:8045-55.
10. Perng, G.C., Ghiasi, H., Kaiwar, R., Nesburn, A.B. and Wechsler, S.L. (1994). An improved method for cloning portions of the repeat regions of herpes simplex virus type 1. J Virol Methods. 46:111-6.
11. Perng, G.C., Zwaagstra, J.C., Ghiasi, H., Kaiwar, R., Brown, D.J., Nesburn, A.B. and Wechsler, S.L. (1994). Similarities in regulation of the HSV-1 LAT promoter in corneal and neuronal cells. Invest Ophthalmol Vis Sci. 35:2981-9.
12. Perng, G.C., Thompson, R.L., Sawtell, N.M., Taylor, W.E., Slanina, S.M., Ghiasi, H., Kaiwar, R., Nesburn, A.B. and Wechsler, S.L. (1995). An avirulent ICP34.5 deletion mutant of herpes simplex virus type 1 is capable of in vivo spontaneous reactivation. J Virol. 69:3033-41.
13. Perng, G.C., Ghiasi, H., Slanina, S.M., Nesburn, A.B. and Wechsler, S.L. (1996). High-dose ocular infection with a herpes simplex virus type 1 ICP34.5 deletion mutant produces no corneal disease or neurovirulence yet results in wild-type levels of spontaneous reactivation. J Virol. 70:2883-93.
14. Ghiasi, H., Perng, G.C., Cai, S., Nesburn, A.B. and Wechsler, S.L. (1996). The UL3 open reading frame of herpes simplex virus type 1 codes for a phosphoprotein. Virus Res. 44:137-42.
15. Perng, G.C., Chokephaibulkit, K., Thompson, R.L., Sawtell, N.M., Slanina, S.M., Ghiasi, H., Nesburn, A.B. and 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. J Virol. 70:282-91.
16. Perng, G.C., Ghiasi, H., Slanina, S.M., Nesburn, A.B. and Wechsler, S.L. (1996). The spontaneous reactivation function of the herpes simplex virus type 1 LAT gene resides completely within the first 1.5 kilobases of the 8.3-kilobase primary transcript. J Virol. 70:976-84.
17. Perng, G.C., Slanina, S.M., Ghiasi, H., Nesburn, A.B. and Wechsler, S.L. (1996). A 371-nucleotide region between the herpes simplex virus type 1 (HSV-1) LAT promoter and the 2-kilobase LAT is not essential for efficient spontaneous reactivation of latent HSV-1. J Virol. 70:2014-8.
18. Drolet, B.S., Perng, G.C., Cohen, J., Slanina, S.M., Yukht, A., Nesburn, A.B. and Wechsler, S.L. (1998). The region of the herpes simplex virus type 1 LAT gene involved in spontaneous reactivation does not encode a functional protein. Virology. 242:221-32.
19. Carr, D.J., Halford, W.P., Veress, L.A., Noisakran, S., Perng, G.C. and Wechsler, S.L. (1998). The persistent elevated cytokine mRNA levels in trigeminal ganglia of mice latently infected with HSV-1 are not due to the presence of latency associated transcript (LAT) RNAs. Virus Res. 54:1-8.
20. Loutsch, J.M., Perng, G.C., Hill, J.M., Zheng, X., Marquart, M.E., Block, T.M., Ghiasi, H., Nesburn, A.B. and Wechsler, S.L. (1999). Identical 371-base-pair deletion mutations in the LAT genes of herpes simplex virus type 1 McKrae and 17syn+ result in different in vivo reactivation phenotypes. J Virol. 73:767-71.
21. Drolet, B.S., Perng, G.C., Villosis, R.J., Slanina, S.M., Nesburn, A.B. and Wechsler, S.L. (1999). Expression of the first 811 nucleotides of the herpes simplex virus type 1 latency-associated transcript (LAT) partially restores wild-type spontaneous reactivation to a LAT-null mutant. Virology. 253:96-106.
22. Ghiasi, H., Perng, G.C., Nesburn, A.B. and Wechsler, S.L. (1999). Either a CD4(+)or CD8(+)T cell function is sufficient for clearance of infectious virus from trigeminal ganglia and establishment of herpes simplex virus type 1 latency in mice. Microb Pathog. 27:387-94.
23. Ghiasi, H., Cai, S., Perng, G.C., Nesburn, A.B. and Wechsler, S.L. (1999). Perforin pathway is essential for protection of mice against lethal ocular HSV-1 challenge but not corneal scarring. Virus Res. 65:97-101.
24. Ghiasi, H., Hofman, F.M., Cai, S., Perng, G.C., Nesburn, A.B. and Wechsler, S.L. (1999). Vaccination with different HSV-1 glycoproteins induces different patterns of ocular cytokine responses following HSV-1 challenge of vaccinated mice. Vaccine. 17:2576-82.
25. Ghiasi, H., Cai, S., Slanina, S.M., Perng, G.C., Nesburn, A.B. and Wechsler, S.L. (1999). The role of interleukin (IL)-2 and IL-4 in herpes simplex virus type 1 ocular replication and eye disease. J Infect Dis. 179:1086-93.
26. Ghiasi, H., Perng, G.C., Hofman, F.M., Cai, S., Nesburn, A.B. and Wechsler, S.L. (1999). Specific and nonspecific immune stimulation of MHC-II-deficient mice results in chronic HSV-1 infection of the trigeminal ganglia following ocular challenge. Virology. 258:208-16.
27. Perng, G.C., Slanina, S.M., Yukht, A., Ghiasi, H., Nesburn, A.B. and Wechsler, S.L. (1999). Herpes simplex virus type 1 serum neutralizing antibody titers increase during latency in rabbits latently infected with latency-associated transcript (LAT)-positive but not LAT-negative viruses. J Virol. 73:9669-72.
28. Perng, G.C., Slanina, S.M., Yukht, A., Drolet, B.S., Keleher, W., Jr., Ghiasi, H., Nesburn, A.B. and Wechsler, S.L. (1999). A herpes simplex virus type 1 latency-associated transcript mutant with increased virulence and reduced spontaneous reactivation. J Virol. 73:920-9.
29. Ghiasi, H., Cai, S., Perng, G.C., Nesburn, A.B. and Wechsler, S.L. (2000). Both CD4+ and CD8+ T cells are involved in protection against HSV-1 induced corneal scarring. Br J Ophthalmol. 84:408-12.
30. Perng, G.C., Jones, C., Ciacci-Zanella, J., Stone, M., Henderson, G., Yukht, A., Slanina, S.M., Hofman, F.M., Ghiasi, H., Nesburn, A.B. and Wechsler, S.L. (2000). Virus-induced neuronal apoptosis blocked by the herpes simplex virus latency-associated transcript. Science. 287:1500-3.
31. Perng, G.C., Slanina, S.M., Yukht, A., Ghiasi, H., Nesburn, A.B. and Wechsler, S.L. (2000). The latency-associated transcript gene enhances establishment of herpes simplex virus type 1 latency in rabbits. J Virol. 74:1885-91.
32. Ghiasi, H., Cai, S., Perng, G.C., Nesburn, A.B. and Wechsler, S.L. (2000). The role of natural killer cells in protection of mice against death and corneal scarring following ocular HSV-1 infection. Antiviral Res. 45:33-45.
33. Ghiasi, H., Perng, G.C., Nesburn, A.B. and Wechsler, S.L. (2000). Antibody-dependent enhancement of HSV-1 infection by anti-gK sera. Virus Res. 68:137-44.
34. Inman, M., Perng, G.C., Henderson,G., Ghiasi. H., Nesburn, A.B., Wechsler, S.L., and Jones, C. (2001) Localization of DNA sequences in the latency-associated transcript (LAT) gene of herpes simplex virus type 1 that promote cell survival and spontaneous reactivation. J.Virol. 75(8):3636-46.
35. Ghiasi, H., Hofman, F.M., Wallner, K., Cai, S., Perng, G.C., Nesburn, A.B., and Wechsler, S.L.. (2000). Corneal macrophage infiltrates following ocular herpes simplex virus type 1 challenge vary in BALB/c mice vaccinated with different vaccines. Vaccine 19:1266-73.
36. Perng, G.C., Slanina, S.M., Ghiasi, H., Nesburn, A.B., and Wechsler, S.L.. (2001) The effect of LAT (latency associated transcript) on the herpes simplex virus type 1 (HSV 1) latency-reactivation phenotype is mouse strain dependent. J.g.Virol, 82(Pt 5):1117-22.
37. Samoto, K., Perng, G.C., Ehtesham, M., Liu, Y., Wechsler, S.L., Nesburn, A.B., Black, K.L., and Yu, J.S.. (2001). A herpes simplex virus type 1 mutant deleted for ?34.5 and LAT kills glioma cells in vitro and is inhibited for in vivo reactivation. Cancer Gene Therapy, 8(4):269-77.
38. Perng, G.C., Esmaili, D., Slanina, S.M., Yukht, A., Ghiasi, H., Osorio N., Mott, K.R., Maguen, B., Jin, L., Nesburn, A.B., and Wechsler, S.L.. (2001). Three herpes simplex virus type 1 latency-associated transcript mutants with distinct and asymmetric effects on virulence in mice compared with rabbits. J. Virol.,75(19):9018-9028.
39. Ghiasi, H., Osorio, Y., Perng, G.C., Nesburn, A.B., and Wechsler, S.L..(2001). Recombinant Herpes Simplex Virus Type 1 Expressing Murine Interleukin-4 Is Less Virulent than Wild-Type Virus in Mice. J Virol.,75(19):9029-36.
40. Perng, G.C., Maguen, B., Jin, L., Mott, K.R., Osorio, N., Slanina, S.M., Yukht, A., Ghiasi, H., Nesburn, A.B., Inman, M., Henderson, G., Jones, C., and Wechsler, S.L..(2002). A gene capable of blocking apoptosis can substitute for the herpes simplex virus type 1 latency-associated transcript gene and restore wild-type reactivation levels. J Virol.76(3):1224-35.
41. Samoto, K., Ehtesham, M., Perng, G.C., Hashizume, K., Wechsler, S.L., Nesburn, A.B., Black, K.L., and Yu, J.S.. (2002). A Herpes Simplex Virus Type 1 Mutant with ?34.5 and LAT Deletions Effectively Oncolyses Human U87 Glioblastomas in Nude Mice.Neurosurgery.50(3):599-606.
42. Moxley, M.J., Block, M.T., Liu, H.C., Fraser, N.W., Perng, G.C., Wechsler, S.L., and Su, Y.H.. (2002). Herpes simplex virus type 1 infection prevents detachment of nerve growth factor-differentiated PC12 cells in culture. J. g.Virol, 83, 1591-1600.
43. Osario, Y., Sharifi, B.G., Perng, G.C., Ghiasi, N.S., and Ghiasi, H.. (2002). The role of TH1 and TH2 cytokines in HSV-1 induced corneal scarring. Ocul. Immunol. Inflamm.2002. Jun; 10(2):105-16.
44. Perng, G.C., Maguen, B., Jin, L., Mott, K.R., Benmohamed, L., Yukht, A., Osorio, N., Nesburn, A.B., Henderson, G., Inman, M., Jones, C., and Wechsler, S.L.. (2002). A novel herpes simplex virus type 1 (HSV 1) transcript (AL RNA) antisense to the 5’ end of LAT (latency associated transcript) produces a protein in infected rabbits. J.Virol. 76(16):8003-8010.
45. Ghiasi, H., Osorio, Y., Perng, G.C., Nesburn, A.B., and Wechsler, S.L.. (2002). Overexpression of Interleukin-2 by a Recombinant Herpes Simplex Virus Type 1 Attenuates Pathogenicity and Enhances Antiviral Immunity. J.Virol. 2002. 76(18): 9069-9078.
46. Ghiasi, H., Osorio, Y., Hedvat, Y., Perng, G.C., Nesburn, A.B., and Wechsler, S.L.. (2002). Infection of BALB/c Mice with a Herpes Simplex Virus Type 1 Recombinant Virus Expressing IFN-gamma Driven by the LAT Promoter. Virology (302): 144-154.
47. Perng, G.C., Mott, K.R., Osorio, N., Yukht, A., Salina, S., Nguyen, Q.H. , Nesburn, A.B., and Wechsler, S.L.. (2002). Herpes simplex virus type 1 (HSV 1) mutants containing the KOS HSV 1 strain ICP34.5 gene in place of the HSV 1 McKrae ICP34.5 gene have McKrae-like spontaneous reactivation and non Mckrae-like virulence. J.g. Virol, 83, 2933-2942.
48. Henderson, G., Peng, W., Jin, L., Perng, G.C., Nesburn, A.B., Wechsler, S.L., and Jones, C..(2002). Regulation of caspase 8 and caspase 9 induced apoptosis by the herpes simplex virus type 1 (HSV 1) latency associated transcript (LAT). J Neurovirol. (8) Suppl 2:103-11.
49. Jin, L., Peng, W., Perng, G.C., Brick, D.J., Nesburn, A.B., Jones, C., and Wechsler, S.L.. (2003).Identification of herpes simplex virus type 1 (HSV-1) latency associated transcript (LAT) sequences that both inhibit apoptosis and enhance the spontaneous reactivation phenotype. J. Viol. 2003. 77(11):6556-61.
50. Peng, W., Henderson, G., Perng, G.C., Nesburn, A.B., Wechsler, S.L. and Jones, C. (2003) The herpes simplex virus type 1 (HSV 1) latency associated transcript (LAT) promotes splicing of the Bcl-x transcript to Bcl-xL, which encodes an anti-apoptosis protein, rather than to Bcl-xS which encodes a pro-apoptotic protein. J.Virol. In Press.
51. Mott, K.R., Osorio, N., Jin, L., Brick, D.J., Naito, J., Cooper, J., Henderson, G., Inman, M., Jones, C., Wechsler, S.L., and Perng, G.C. (2003). The BHV-1 LR ORF-2 is critical for this gene’s ability to restore the high wild type reactivation phenotype to an HSV-1 LAT null mutant. J gen Virol.84:2875-2989.
52. Henderson G, Perng GC, Nesburn AB, Wechsler SL, and Jones C (2004). The latency related (LR) gene encoded by bovine herpesvirus (BHV-1) can suppress caspase 3 and Caspase 9 cleavage during productive infection. J. Neurovirol.10(1):64-70.
53. L Jin, GC Perng, DJ Brick, J Naito, AB Nesburn, C Jones, and SL Wechsler. (2004). Methods for detecting the HSV-1 LAT anti-apoptosis activity in virus infected tissue culture cells. Submitted to Journal. Virol. Methods. 118(1):9-13.
54.Drolet B., Mott K.R., Wechsler S.L., Perng, G.C. (2003). Gylcoprotein C of herpes simplex virus type 1 is required to cause corneal disease at low infectious doses in intact cornea. Curent Eye Research. In Press.
55. Barsam CA, Brick DJ, Jones C, Wechsler SL, Perng G.C. (2004). Infection of rabbit eyes ocularly with a high spontaneous reactivation phenotype HSV-1 mutant may provide a good and reproducible mdoel to study the causes of sever corneal scarring. Cornea. In Press.
56. Julie Naito, Ruma Mukerjee, Kevin R. Mott, Wen Kang, Nelson Osorio, Nigel W. Fraser, and Guey-Chuen Perng. (2004). Identification of a protein encoded in the herpes simplex virus type 1 latency associated transcript promoter region. Virus Research. In Press.
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Immunology and Pathogenesis
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https://faculty.uci.edu/profile/?facultyId=4961
https://faculty.uci.edu/profile/?facultyId=4961
Last updated
10/07/2021
10/07/2021