假性狂犬病毒(Pseudorabies virus, PRV)為alphaherpesviridae成員之一，在成豬的三叉神經節造成潛伏感染(latent infection)，免疫力下降會導致病毒復發(reactivation)，感染其他動物，造成畜牧業經濟損失。PRV在台灣豬場的盛行率高達96%，現行疫苗皆為進口，保護力仍不理想，本研究室分離出適低溫性突變株ts5-7 (temperature- sensitive mutant)，對BALB/c小鼠具有80% 保護力(蔣莉，2001)。本研究以BALB/c小鼠及Vero細胞模式，繼續測定ts5-7潛伏感染及復發之能力，PRV之P7野生型病毒作為陽性對照組。

　　動物實驗方面，取P7抗血清(25倍稀釋)腹腔注射BALB/c小鼠，經30分鐘後，個別鼻點滴接種20 μl P7 (劑量103 TCID50，即0.67 LD50)及ts5-7(劑量103.59 TCID50，即1 LD50)病毒。經90天後存活的小鼠以紫外光(波長為366 nm)照射及尾部靜脈注射地塞米松(dexamethasone)誘導復發。結果顯示，感染P7病毒株90天後存活的小鼠，取三叉神經節以PCR方法(gE1及gE2引子)，可偵測出PRV gE基因的存在，以RT-PCR及nested-PCR則無法偵測到LLT mRNA (引子對分別為LLT-3 / LLT-1及CM3.1 / LLT3.1)，以三叉神經節組織共培養方法，亦無病毒生長。在誘導復發後第8天(即接種病毒後第98天)，檢測出三叉神經節中仍有gE基因，以三叉神經節及肺組織檢體共培養方法，可測得病毒復發生長現象，其機率分別為10%及20%。此外以ELISA偵測誘導復發後第4天及第8天小鼠血清抗體上升，結果顯示，在第4天，10隻小鼠中有2隻小鼠血清抗體效價上升；第8天，此2隻小鼠血清效價上升更顯著。感染ts5-7病毒株90天後存活的小鼠則沒有偵測到gE基因及LLT mRNA，復發刺激前後，皆無發現病毒生長，小鼠也皆無任何病徵出現。而誘導復發後(第94及98天)，10隻小鼠中有1隻小鼠血清抗體效價上升。

　　Vero細胞培養模式方面，以胞嘧啶阿拉伯糖核(cytosine arabinoside) (10 μg/ml) 處理細胞5小時後，各別接種100 μl P7 (101 TCID50)與ts5-7 (101.59 TCID50)病毒，培養經過7天後，存活的細胞再以不同的時間紫外光(波長254 nm)照射，誘導復發。結果顯示，兩種病毒感染後存活的細胞，於第4天及7天，可測得gE基因之存在，卻沒有偵測到感染性病毒，亦無LLT mRNA表現。第11天誘導復發之結果顯示，以紫外光照射60秒後復發機率為最高，P7及ts5-7兩種感染復發機率分別為21.8%及9.8%，存活細胞亦有gE基因存在。

　　結論為BALB/c小鼠實驗模式無法偵測到ts5-7之潛伏感染及復發現象，而野生型P7病毒具此能力。至於Vero細胞實驗模式兩種病毒皆可測得潛伏感染及復發現象，但ts5-7復發頻率遠低於P7野生型病毒。

　　Pseudorabies Virus (PRV), a member of the alphaherpesviridae, can cause latent infection in trigeminal ganglia (TG) of infected adult swine. When host’s immunity was suppressed, reactivation may occur and virus was transmitted to uninfected animals causing economic losses in the husbandry industry. Current PRV vaccines used still cannot offer full protection and the PRV prevalence rate in Taiwan swine farms still reaches 96%. We have previously screened a selected temperature- sensitive PRV mutant, ts5-7, which could offer 80% protection against challenge in BALB/c mice. In this research, BALB/c mice and Vero cell culture models were adopted to test ts5-7 mutant’s ability in causing latent infection and subsequent viral reactivation. PRV wild type P7 strain was used as positive control.

　　In animal model, the BALB/c mice were passively immunized by intraperitoneal inoculation with 1:25 diluted anti-PRV P7 mice antiserum. After 30 minutes, the pre-immunized mice were infected by intranasal inoculation with 20 μl of 103 TCID50 (i.e. 0.67 LD50) of P7 and 103.59 TCID50 (i.e. 1LD50) of ts5-7 mutant, respectively. After 90 days, some of the surviving mice were irradiated by ultraviolet light (UV, 366 nm) and intravenously inoculated with dexamethasone for inducing viral reactivation. The remaining mice were scarified for viral DNA detection. The results showed the viral glycoprotein E (gE) gene could be detected by PCR (gE1 and gE2 primers) in TG of P7-infected mice, but not in ts5-7 infected group. However, the supposed latency- associated LLT mRNA could be detected neither by RT-PCR using LLT-1 and LLT-3 primers, nor by nested-PCR using CM3.1 and LLT3.1 primers. Negative results were obtained by explant co-culture. On the 8th day after induction, viral gE was also detected in P7-infected mice but not in ts5-7 infected group. Moreover, the explant co-cultures with lung and TG tissues were successful in virus isolation in P7-infected mice (20% and 10% positive rates, respectively). In contrast, negative results were obtained for ts5-7 infected group. Furthermore, sera from 2 of 10 P7-infected mice showed antibody rising against PRV on the 4th and the 8th days after induction. Sera from 1 of 10 ts5-7 infected mice also showed antibody rising. No clinical signs were noted during latency or after reactivation in all mice.

　　In cell culture model, cells were pre-fed with cytosine arabinoside for 5 hours, then infected with P7 or ts5-7. The infected Vero cells were subsequently cultivated for 11 days. On the 7th day of culture, survived cells were irradiated with ultraviolet (wavelength 254 nm) for inducing viral reactivation. The viral gE gene for survived cells on the 4th and 7th days can be detected for both viral infections. However, LLT mRNA and active viral replication could not be found. On the 11th day, the highest frequency of virus reactivation was detected with UV irradiation for 60 seconds. Frequencies were 21.8% and 9.8% for P7 and ts5-7 infection, respectively. All survived cells also showed the presence of gE gene.

　　These findings indicate that ts5-7 latent-infection and reactivation can be detected in Vero cell model, but the frequency of reactivation is lower than P7 infection. BALB/c mice model for this experiment was failed for ts5-7 mutant, however.

蔣莉. (2001). 豬假性狂犬病毒適低溫性病毒株之分離及其免疫保護力分析。國立成功大學生物研究所碩士論文。

Babic, N., Mettenleiter, T. C., Ugolini, G., Flamand, A., and Coulon, P. (1994). Propagation of pseudorabies virus in the nervous system of the mouse after intranasal inoculation. Virology 204：616-525.

Babic, N., Klupp, B., Brack, A., Mettenleiter, T. C., Ugolini, G., and Flamand, A. (1996). Deletion of glycoprotein gE reduces the propagation of pseudorabies virus in the nervous system of mice after intranasal inoculation. Virology 219：279-284.

Baskerville, A., McFerran, J. B., and Dow, C. (1973). Aujeszky’s disease in pigs. The Veterinary Bulletin 43：466-480.

Belak, S., Ballagi-Pordany, A., Flensburg, J., and Virtanen, A. (1989). Detection of pseudorabies virus DNA sequences by the polymerase chain reaction. Archives of Virology 108：279-286.

Ben-Porat, T., DeMarchi, J. D., Pendrys, J., Ruth, C., and Kaplan, A. S. (1986). Protein specified by the short pseudorabies virus play a role in the release of virus from certain cell. Journal of Virology 57：191-196.

Beran, G. W., Davis, E. B., Arambulo, P. V., Will, C. A., Hill, H. T., and Rock, D. L. (1980). Persistence of pseudorabies virus in infected swine. Journal of the American Veterinary Medical Association 176：998-1000.

Bloom, D. C., Hill, J. M., Devi-Rao, G., Wagner, E. K., Feldman, L. T., and Stevens, J. G. (1996). A 348-base-pair region in the latency-associated transcript facilitates herpes simplex virus type 1 reactivation. Journal of Virology 70：2449-2459.

Brockmeier, S. L., Lager, K. M., and Mengeling, W. L. (1993). Comparison of in vivo reactivation, in vitro reactivation, and polymerase chain reaction for detection of latent pseudorabies virus infection in swine. Journal of Veterinary Diagnostic Investigation 5：505-509.

Brown, T. M., Osorio, F. A., and Rock, D. L. (1990). Detection of latent pseudorabies virus in swine using in situ hybridization. Veterinary Microbiology 24：273-280.

Burge, B. W., and Pfefferkorn, A. (1965). Conditional lethal mutants of an animal virus：Identification of two cistrons. Science 148：959-960.

Card, J. P., and Enquist, L. W. (1995). Neurovirulence of pseudorabies virus. Critical Reviews in Neurobiology 9：137-162.

Card, J. P., Levitt, P., amd Enquist, L. W. (1998). Different patterns of neuronal infection after intracerebral injection of two strains of pseudorabies virus. Journal of Virology 72：4434-4441.

Cheung, A. K. (1994). Detection of the large latency transcript of pseudorabies virus by RNA-PCR and its potential in diagnosis. Journal of Veterinary Diagnostic Investigation 6：483-486.

Cheung, A. K. (1995). Investigation of pseudorabies virus DNA and RNA in trigeminal ganglia and tonsil tissues of latently infected swine. American Journal of Veterinary Research 56：45-50.

Chong, Y. C., and Forster, U. (1987). Relative rates of Aujeszky's disease virus attenuation, as assessed in mice. Veterinary Microbiology 15：249-256.

Clements, G. B., and Subak-Sharpe, J. H. (1988). Herpes simplex virus type 2 establishes latency in the mouse footpad. Journal of General Virology 69：375-383.

Colberg-Poley, A. M., Isom, H. C., and Rapp, F. (1979). Reactivation of herpes simplex virus type 2 from a quiescent state by human cytomegalovirus. Proceedings of the National Academy of Sciences of the United States of America 76：5948-5951.

Cook, S. D., Paveloff, M. J., Doucet, J. J., Cottingham, A. J., Sedarati, F., and Hill, J. M. (1991). Ocular herpes simplex virus reactivation in mice latently infected with latency-associated transcript mutants. Investigative Ophthalmology & Visual Science 32：1558-1561.

Dahlberg, J. E. (1968). Physical and genetic properties of Newcastle disease virus. Ph. D. Thesis Purdie University.

Danaher, R. J., Jacob, R. J., Chorak, M. D., Freeman, C. S., and Miller, C. S. (1999). Heat stress activates production of herpes simplex virus type 1 from quiescently infected neurally differentiated PC12 cells. Journal of Neurovirology 5：374-383.

Danaher, R. J., Jacob, R. J., and Miller, C. S. (1999). Establishment of a quiescent herpes simplex virus type 1 infection in neurally-differentiated PC12 cells. Journal of Neurovirology 5：258-267.

Danaher, R. J., Jacob, R. J., and Miller, C. S. (2000). Herpesvirus quiescence in neuronal cells: antiviral conditions not required to establish and maintain HSV-2 quiescence. Journal of Neurovirology 6：296-302.

Davis-Poynter, N., Bell, S., Minson, T., and Browne, H. (1994). Analysis of the contributions of herpes simplex virus type 1 membrane proteins to the induction of cell-cell fusion. Journal of Virology 68：7586-7590.

De Leeuw, P., and Van Oischot, J. (1985). Intranasal vaccination of pigs against Aujeszky’s disease. Comparison with inactivated vaccines in pigs with low maternal antibody titres. Research of Veterinary Science 39：24-38.

Donofrio, G., Cavirani, S., and van Santen, V. L. (2000). Establishment of a cell line persistently infected with bovine herpesvirus-4 by use of a recombinant virus. Journal of General Virology 81：1807-1814.

Enquist, L. W., Husak, P. J., Banfield, B. W., and Smith, G. A. (1998). Infection and spread of alphaherpesviruses in the nervous system. [Review] Advances in Virus Research 51：237-347.

Enquist, L. W., Tomishima, M. J., Gross, S., and Smith, G. A. (2002). Directional spread of an alpha-herpesvirus in the nervous system. Veterinary Microbiology 86：5-16.

Fuller, A. O., Santos, R. E., and Spear, P. G. (1989). Neutralizing antibodies specific for glycoprotein H of herpes simplex virus permit viral attachment to cells but prevent penetration. Journal of Virology 63：3435-3443.

Furrarah, A. M., and Sweet, C. (1994). Studies of the pathogenesis of wild-type virus and six temperature-sensitive mutants of mouse cytomegalovirus. Journal of Medical Virology 43：317-330.

Golais, F., Sabo, A., and Rajcani, J. (1978). Latent pseudorabies virus infection established at supraoptimal temperature. Acta Virologica. English Ed 22：464-469.

Golais, F., and Sabo A. (1979). The effect of antibody on latent pseudorabies virus infection in vitro. Acta Virologica. English Ed 23：468-472.

Gordon, Y. J. (1990). Pathogenesis and latency of herpes simplex virus type 1 (HSV-1): an ophthalmologist's view of the eye as a model for the study of the virus-host relationship. [Review] Advances in Experimental Medicine & Biology 278：205-209.

Gutekunst, D. E. (1979). Latent pseudorabies virus infection in swine detected by RNA-DNA hybridization. American Journal of Veterinary Research 40：1568-1572.

Hadorn, E. (1951). Developmental action of lethal factors in drosophila. Advances in Genetics 4：53-85.

Halford, W. P., Gebhardt, B. M., and Carr, D. J. (1996). Mechanisms of herpes simplex virus type 1 reactivation. Journal of Virology 70：5051-5060.

Hammer, S. M., Richter, B. S., and Hirsch, M. S. (1981). Activation and suppression of herpes simplex virus in a human T lymphoid cell line. Journal of Immunology 127：144-148.

Hampl, H., Ben-Porat, T., Ehrlicher, L., Habermehl, K. O., and Kaplan, A. S. (1984). Characterization of the envelope proteins of pseudorabies virus. Journal of Virology 52:583-590.
Harris, R. A., Everett, R. D., Zhu, X. X., Silverstein, S., and Preston, C. M. (1989). Herpes simplex virus type 1 immediate-early protein Vmw110 reactivates latent herpes simplex virus type 2 in an in vitro latency system. Journal of Virology 63：3513-3515.

Harris, R. A., and Preston, C. M. (1991). Establishment of latency in vitro by the herpes simplex virus type 1 mutant in1814. Journal of General Virology 72：907-913.

Hasebe, H., Wheeler, J. G., and Osorio, F. A. (1993). Gene specific assay to differentiate strains of pseudorabies virus. Veterinary Microbiology 34：221-231.

Hill, J. M., Field, H. J., and Blyth, W. A. (1975). Acute and recurrent infection with herpes simplex virus in the mouse: a model for studying latency and recurrent disease. Journal of General Virology 28：341-353.

Hung, T., Mummaw, J. G., Wigdahl, B. L., Fang, Z. Y., Huaying, J., and Rapp, F. (1984). Ultrastructural changes during herpes simplex virus type 2 latency and reactivation in vitro. Intervirology 21：5-16.

Jamieson, D. R., Robinson, L. H., Daksis, J. I., Nicholl, M. J., and Preston, C. M. (1995). Quiescent viral genomes in human fibroblasts after infection with herpes simplex virus type 1 Vmw65 mutants. Journal of General Virology 76：1417-1431.

Jestin, A., Foulon, T., Pertuiset, B., Blanchard, P., and Labourdet, M. (1990). Rapid detection of pseudorabies virus genomic sequences in biological samples from infected pigs using polymerase chain reaction DNA amplification. Veterinary Microbiology 23：317-328.

Jin, L., and Scherba, G. (1999). Expression of the pseudorabies virus latency-associated transcript gene during productive infection of cultured cells. Journal of Virology 73：9781-9788.

Jones, C., Newby, T. J., Holt, T., Doster, A., Stone, M., Ciacci-Zanella, J., Webster, C. J., and Jackwood, M. W. (2000). Analysis of latency in cattle after inoculation with a temperature sensitive mutant of bovine herpesvirus 1 (RLB106). Vaccine 18：3185-3195.

Knapp, A. C., Husak, P. J., and Enquist, L. W. (1997). The gE and gI homologs from two alphaherpesviruses have conserved and divergent neuroinvasive properties. Journal of Virology 71：5820-5827.

Kondo, Y., Yura, Y., Iga, H., Yanagawa, T., Yoshida, H., Furumoto, N., and Sato, M. (1990). Effect of hexamethylene bisacetamide and cyclosporin A on recovery of herpes simplex virus type 2 from the in vitro model of latency in a human neuroblastoma cell line. Cancer Research 50：7852-7857.

Kritas, S. K., Pensaert, M. B., and Mettenleiter, T. C. (1994). Invasion and spread of single glycoprotein deleted mutants of Aujeszky's disease virus (ADV) in the trigeminal nervous pathway of pigs after intranasal inoculation. Veterinary Microbiology 40：323-234.

Litwinska, B., Trzcinska, A., and Kantoch, M. (2001). Temperature sensitive mutant of Herpes simplex virus type 1. II. Neurovirulence and latency. Medycyna Doswiadczalnai Mikrobiologia 53：89-99.

Lokensgard, J. R., Thawley, D. G., and Molitor, T. W. (1990). Pseudorabies virus latency: restricted transcription. Archives of Virology 110：129-136.

Lokensgard, J. R., Thawley, D. G., and Molitor, T. W., (1991). Enzymatic amplification of latent pseudorabies virus nucleic acid sequences. Journal of Virological Methods 34：45-55.

Maes, R. K., Sussman, M. D., Vilnis, A., and Thacker, B. J. (1997). Recent developments in latency and recombination of Aujeszky's disease (pseudorabies) virus. [Review] Veterinary Microbiology 55：13-27.

Maggioncalda, J., Mehta, A., Bagasra, O., Fraser, N. W., and Block, T. M. (1996). A herpes simplex virus type 1 mutant with a deletion immediately upstream of the LAT locus establishes latency and reactivates from latently infected mice with normal kinetics. Journal of Neurovirology 2：268-278.

Mathews, R. E. F. (1982). Classification and nomenclature of viruses fourth report of the international committee on taxonomy of viruses. Intervirology 17：1-199.

McFarlane, R. G., Thawley, D. G., and Solorzano, R. F. (1986). Detection of latent pseudorabies virus in porcine tissue, using a DNA hybridization dot-blot assay. American Journal of Veterinary Research 47：2329-2336.

McGeoch, D. J., and Cook, S. (1994). Molecular phylogeny of the alphaherpesvirinae subfamily and a proposed evolutionary timescale. Journal of Molecular Biology 238：9-22.

Mengeling, W. L., Lager, K. M., Volz, D. M., and Brockmeier, S. L. (1992). Effect of various vaccination procedures on shedding, latency, and reactivation of attenuated and virulent pseudorabies virus in swine. American Journal of Veterinary Research 53：2164-2173.

Mettenleiter, T. C. (2000). Aujeszky's disease (pseudorabies) virus: the virus and molecular pathogenesis--state of the art, June 1999. [Review] [99 refs] Veterinary Research 31：99-115.

Mettenleiter, T. C., Schreurs, C., Zuckermann, F., Ben-Porat, T., and Kaplan, A. S. (1988). Role of glycoprotein gIII of pseudorabies virus in virulence. Journal of Virology 62：2712-2717.

Mosmann, T. (1983). Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65：55-63.

Mulder, W. A., Jacobs, L., Priem, J., Kok, G. L., Wagenaar, F., Kimman T. G., and Pol, J. M. (1994). Glycoprotein gE-negative pseudorabies virus has a reduced capability to infect second- and third-order neurons of the olfactory and trigeminal routes in the porcine central nervous system. Journal of General Virology 75：3095-3106.

O'Neill, F. J., Goldberg, R. J., and Rapp, F. (1972). Herpes simplex virus latency in cultured human cells following treatment with cytosine arabinoside. Journal of General Virology 14：189-197.

O'Neill, F. J. (1977). Prolongation of herpes simplex virus latency in cultured human cells by temperature elevation. Journal of Virology 24：41-46.

Osorio, F. A., and Rock, D. L. (1992). A murine model of pseudorabies virus latency. Microbial Pathogenesis 12：39-46.

Platt, K. B., Mare, C. J., and Hinz, P. N. (1980). Differentiation of vaccine strains and field isolates of pseudorabies (Aujeszky's disease) virus: trypsin sensitivity and mouse virulence markers. Archives of Virology 63：107-114.

Preston, C. M. (2000). Repression of viral transcription during herpes simplex virus latency. [Review] Journal of General Virology 81：1-19.

Pringle, C. R. (1968). Recombination between conditional lethal mutants within a strain of foot-and-mouth disease virus. Journal of General Virology 2：199-202.

Rebecca, S. (2000). History and characterization of the vero cell line. The vaccine and related biological products advisory committee meeting to be held on May 12.

Rock, D. L., Hagemoser, W. A., Osorio, F. A., and McAllister, H. A. (1988). Transcription from the pseudorabies virus genome during latent infection. Brief report. Archives of Virology 98：99-106.

Roizman, B. (1965). Abortive infection of canine cells by herpes simplex virus III. The interference of conditional lethal virus with an extended host range mutant. Virology 27：113-117.

Romero, C. H., Rowe, C. A., Wentz, I., and Marques, J. L. (1991). Non-pathogenic strains of Aujeszky's disease virus are not reactivated in swine after corticosteroid treatment. Brazilian Journal of Medical & Biological Research 24：99-106.

Russell, J., and Preston, C. M. (1986). An in vitro latency system for herpes simplex virus type 2. Journal of General Virology 67：397-403.

Russell, J., Stow, N. D., Stow, E. C., and Preston, C. M. (1987). Herpes simplex virus genes involved in latency in vitro. Journal of General Virology 68：3009-3018.

Sabo, A., and Rajcani, J. Latent pseudorabies virus infection in pigs. (1976). Acta Virologica 20：208-214.

Sawtell, N. M., Poon, D. K., Tansky, C. S., and 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 72：5343-5350.

Schang, L. M., Kutish, G. F., and Osorio, F. A. (1994). Correlation between precolonization of trigeminal ganglia by attenuated strains of pseudorabies virus and resistance to wild-type virus latency. Journal of Virology 68：8470-8406.

Schang, L. M., and Osorio, F. A. (1994). Quantitation of latency established by attenuated strains of Pseudorabies (Aujeszky's disease) virus. Journal of Virological Methods 50：269-280.

Scheck, A. C., Wigdahl, B., and Rapp, F. (1989). Transcriptional activity of the herpes simplex virus genome during establishment, maintenance, and reactivation of in vitro virus latency. Intervirology 30：121-136.

Scherba, G., Jin, L., Schnitzlein, W. M., and Vodkin, M. H. (1992). Differential polymerase chain reaction for detection of wild-type and a vaccine strain of Aujeszky's disease (pseudorabies) virus. Journal of Virological Methods 38：131-143.

Shibata, I., Inaba, Y., and Akashi, H. (1991). Avirulent ts and thymidine kinase-deficient mutant of Aujeszky’s disease virus. Journal of Veterinary Medical Science 53：663-670.

Shibata, I., Hatano, Y., and Inaba, Y. (1992). Multiplication and immunogenicity of a temperature-sensitive and thymidine kinase deficient strain of Aujeszky’s disease virus in pigs. Journal of Veterinary Medical Science 54：1111-1115.

Shimeld, C., Hill, T.J., Blyth, W.A., and Easty, D.L. (1989). An improved model of recurrent herpetic eye disease in mice. Current Eye Research 8： 1193-1204.

Shimeld, C., Hill, T.J., Blyth, W.A., and Easty, D.L. (1990). Reactivation of latent infection and induction of recurrent herpetic eye disease in mice. Journal of General Virology 71: 379-404.

Smith, G. A., Gross, S. P., and Enquist, L. W. (2001). Herpesviruses use bidirectional fast-axonal transport to spread in sensory neurons. Proceedings of the National Academy of Sciences of the United States of America 98：3466-3470.

Stevens, J. G., and Cook, M. L. (1971). Latent herpes simplex virus in spinal ganglia of mice. Science 173：843-845.

Tanaka, S., Imamura, T., Sakaguchi, M., and Mannen, K. (1998). Acetylcholine reactivates latent pseudorabies virus in mice. Journal of Virological Methods 70：103-106.

Thompson, R. L., and Sawtell, N. M. (1997). The herpes simplex virus type 1 latency-associated transcript gene regulates the establishment of latency. Journal of Virology 71：5432-5440.

Todd, D., Hull, J., and McFerran, B. (1987). Comparison of Aujeszky’s disease (Pseudorabies) virus strain by SDS-PAGE of the virus protein. Archive of Virology 92：301-307.

Tomishima, M. J., Smith, G. A., and Enquist, L. W. (2001). Sorting and transport of alpha herpesviruses in axons. [Review] Traffic 2：429-436.

Tullo, A. B., Shimeld, C., Blyth, W. A., Hill, T. J., and Easty, D. L. (1982). Spread of virus and distribution of latent infection following ocular herpes simplex in the non-immune and immune mouse. Journal of General Virology 63：95-101.

Van Oirschot, J. T., and Gielkens, A. L. (1984). In vivo and in vitro reactivation of latent pseudorabies virus in pigs born to vaccinated sows. American Journal of Veterinary Research 45：567-571.

Wagner, E. K., and Bloom, D. C. (1997). Experimental investigation of herpes simplex virus latency. [Review] Clinical Microbiology Reviews 10：419-443.

Wheeler, J. G., and Osorio, F. A. (1991). Investigation of sites of pseudorabies virus latency, using polymerase chain reaction. American Journal of Veterinary Research 52：1799-1803.

Wigdahl, B. L., Isom, H. C., De Clercq, E., and Rapp, F. (1982). Activation of herpes simplex virus (HSV) types 1 genome by temperature-sensitive mutants of HSV type 2. Virology 116：468-479.

Wigdahl, B. L., Scheck, A. C., De Clercq, E., and Rapp, F. (1982). High efficiency latency and activation of herpes simplex virus in human cells. Science 217：1145-1146.

Wigdahl, B. L., Ziegler, R. J., Sneve, M., and Rapp, F. (1983). Herpes simplex virus latency and reactivation in isolated rat sensory neurons. Virology 127：159-67.

Wilcox, C. L., and Johnson, E. M. Jr. (1988). Characterization of nerve growth factor-dependent herpes simplex virus latency in neurons in vitro. Journal of Virology 62：393-399.

Wilcox, C. L., Smith, R. L., Freed, C. R., and Johnson, E. M. Jr. (1990). Nerve growth factor-dependence of herpes simplex virus latency in peripheral sympathetic and sensory neurons in vitro. Journal of Neuroscience 10：1268-1275.

Wittmann, G. (1991). Spread and control of Aujeszky’s disease (AD). Comparative Immunology, Microbiology and Infectious Diseases 14：165-173.

Youssoufian, H., Hammer, S. M., Hirsch, M. S., and Mulder, C. (1982). Methylation of the viral genome in an in vitro model of herpes simplex virus latency. Proceedings of the National Academy of Sciences of the United States of America 79：2207-2210.

Zsak, L., Zuckermann, F., Sugg, N., and Ben-Porat, T. (1992). Glycoprotein gI of pseudorabies virus promotes cell fusion and virus spread via direct cell-to-cell transmission. Journal of Virology 66：2316-2325.

Zsak, L., Mettenleiter, T. C., Sugg, N., and Ben-Porat, T. (1989). Release of pseudorabies virus from infected cells is controlled by several viral functions and is modulated by cellular components. Journal of Virology 63：5475-5477.