Abstract
Herpes simplex virus is most probably maintained in the ganglion neurons of the peripheral nervous system of humans in a latent form that can reactivate to produce recurrent disease. As an approximation of this cell-virus interaction, we have constructed a herpes simplex virus latency in vitro model system using human fetus sensory neurons as the host cell. Human fetus neurons were characterized as neuronal in origin by the detection of the neuropeptide substance P and the neuron-specific plasma membrane A2B5 antigen. Virus latency was established by blocking complete expression of the virus genome by treatment of infected human neurons with a combination of human leukocyte interferon and (E)-5-(2-bromovinyl)-2'-deoxyuridine for 7 days. After removal of inhibitors, virus latency was maintained for at least 9 days. This in vitro model will provide a system to analyze, in a primary human neuron, the state of the herpes simplex virus genome during establishment and maintenance of experimental latency.
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Selected References
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- Allaudeen H. S., Chen M. S., Lee J. J., De Clercq E., Prusoff W. H. Incorporation of E-5-(2-halovinyl)-2'-deoxyuridines into deoxyribonucleic acids of herpes simplex virus type 1-infected cells. J Biol Chem. 1982 Jan 25;257(2):603–606. [PubMed] [Google Scholar]
- Allaudeen H. S., Kozarich J. W., Bertino J. R., De Clercq E. On the mechanism of selective inhibition of herpesvirus replication by (E)-5-(2-bromovinyl)-2'-deoxyuridine. Proc Natl Acad Sci U S A. 1981 May;78(5):2698–2702. doi: 10.1073/pnas.78.5.2698. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Baringer J. R. Recovery of herpes simplex virus from human sacral ganglions. N Engl J Med. 1974 Oct 17;291(16):828–830. doi: 10.1056/NEJM197410172911606. [DOI] [PubMed] [Google Scholar]
- Colberg-Poley A. M., Isom H. C., Rapp F. Involvement of an early human cytomegalovirus function in reactivation of quiescent herpes simplex virus type 2. J Virol. 1981 Mar;37(3):1051–1059. doi: 10.1128/jvi.37.3.1051-1059.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Eisenbarth G. S., Walsh F. S., Nirenberg M. Monoclonal antibody to a plasma membrane antigen of neurons. Proc Natl Acad Sci U S A. 1979 Oct;76(10):4913–4917. doi: 10.1073/pnas.76.10.4913. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fraser N. W., Lawrence W. C., Wroblewska Z., Gilden D. H., Koprowski H. Herpes simplex type 1 DNA in human brain tissue. Proc Natl Acad Sci U S A. 1981 Oct;78(10):6461–6465. doi: 10.1073/pnas.78.10.6461. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Galloway D. A., Fenoglio C. M., McDougall J. K. Limited transcription of the herpes simplex virus genome when latent in human sensory ganglia. J Virol. 1982 Feb;41(2):686–691. doi: 10.1128/jvi.41.2.686-691.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gerdes J. C., Marsden H. S., Cook M. L., Stevens J. G. Acute infection of differentiated neuroblastoma cells by latency-positive and latency-negative herpes simplex virus ts mutants. Virology. 1979 Apr 30;94(2):430–441. doi: 10.1016/0042-6822(79)90473-2. [DOI] [PubMed] [Google Scholar]
- Honess R. W., Roizman B. Regulation of herpesvirus macromolecular synthesis. I. Cascade regulation of the synthesis of three groups of viral proteins. J Virol. 1974 Jul;14(1):8–19. doi: 10.1128/jvi.14.1.8-19.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kennedy P. G., Clements G. B., Brown S. M. Differential susceptibility of human neural cell types in culture to infection with herpes simplex virus. Brain. 1983 Mar;106(Pt 1):101–119. doi: 10.1093/brain/106.1.101. [DOI] [PubMed] [Google Scholar]
- Kennedy P. G., Lisak R. P., Raff M. C. Cell type-specific markers for human glial and neuronal cells in culture. Lab Invest. 1980 Oct;43(4):342–351. [PubMed] [Google Scholar]
- Levine M., Goldin A. L., Glorioso J. C. Persistence of herpes simplex virus genes in cells of neuronal origin. J Virol. 1980 Jul;35(1):203–210. doi: 10.1128/jvi.35.1.203-210.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nahmias A. J., Roizman B. Infection with herpes-simplex viruses 1 and 2. 1. N Engl J Med. 1973 Sep 27;289(13):667–674. doi: 10.1056/NEJM197309272891305. [DOI] [PubMed] [Google Scholar]
- Nahmias A. J., Roizman B. Infection with herpes-simplex viruses 1 and 2. 3. N Engl J Med. 1973 Oct 11;289(15):781–789. doi: 10.1056/NEJM197310112891505. [DOI] [PubMed] [Google Scholar]
- Nahmias A. J., Roizman B. Infection with herpes-simplex viruses 1 and 2. II. N Engl J Med. 1973 Oct 4;289(14):719–725. doi: 10.1056/NEJM197310042891404. [DOI] [PubMed] [Google Scholar]
- O'Neill F. J., Goldberg R. J., Rapp F. Herpes simplex virus latency in cultured human cells following treatment with cytosine arabinoside. J Gen Virol. 1972 Feb;14(2):189–197. doi: 10.1099/0022-1317-14-2-189. [DOI] [PubMed] [Google Scholar]
- Olson L. C., Buescher E. L., Artenstein M. S., Parkman P. D. Herpesvirus infections of the human central nervous system. N Engl J Med. 1967 Dec 14;277(24):1271–1277. doi: 10.1056/NEJM196712142772401. [DOI] [PubMed] [Google Scholar]
- Price R. W., Walz M. A., Wohlenberg C., Notkins A. L. Latent infection of sensory ganglia with herpes simplex virus: efficacy of immunization. Science. 1975 May 30;188(4191):938–940. doi: 10.1126/science.166432. [DOI] [PubMed] [Google Scholar]
- Showalter S. D., Zweig M., Hampar B. Monoclonal antibodies to herpes simplex virus type 1 proteins, including the immediate-early protein ICP 4. Infect Immun. 1981 Dec;34(3):684–692. doi: 10.1128/iai.34.3.684-692.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Stevens J. G. Latent herpes simplex virus and the nervous system,. Curr Top Microbiol Immunol. 1975;70:31–50. doi: 10.1007/978-3-642-66101-3_2. [DOI] [PubMed] [Google Scholar]
- Wigdahl B. L., Isom H. C., De Clercq E., Rapp F. Activation of herpes simplex virus (HSV) type 1 genome by temperature-sensitive mutants of HSV type 2. Virology. 1982 Jan 30;116(2):468–479. doi: 10.1016/0042-6822(82)90140-4. [DOI] [PubMed] [Google Scholar]
- Wigdahl B. L., Isom H. C., Rapp F. Repression and activation of the genome of herpes simplex viruses in human cells. Proc Natl Acad Sci U S A. 1981 Oct;78(10):6522–6526. doi: 10.1073/pnas.78.10.6522. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wigdahl B. L., Scheck A. C., De Clercq E., Rapp F. High efficiency latency and activation of herpes simplex virus in human cells. Science. 1982 Sep 17;217(4565):1145–1146. doi: 10.1126/science.6180477. [DOI] [PubMed] [Google Scholar]
- Wigdahl B. L., Ziegler R. J., Sneve M., Rapp F. Herpes simplex virus latency and reactivation in isolated rat sensory neurons. Virology. 1983 May;127(1):159–167. doi: 10.1016/0042-6822(83)90380-x. [DOI] [PubMed] [Google Scholar]
- Wigdahl B., Scheck A. C., Ziegler R. J., De Clercq E., Rapp F. Analysis of the herpes simplex virus genome during in vitro latency in human diploid fibroblasts and rat sensory neurons. J Virol. 1984 Jan;49(1):205–213. doi: 10.1128/jvi.49.1.205-213.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Youssoufian H., Hammer S. M., Hirsch M. S., Mulder C. Methylation of the viral genome in an in vitro model of herpes simplex virus latency. Proc Natl Acad Sci U S A. 1982 Apr;79(7):2207–2210. doi: 10.1073/pnas.79.7.2207. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ziegler R. J., Herman R. E. Peripheral infection in culture of rat sensory neurons by herpes simplex virus. Infect Immun. 1980 May;28(2):620–623. doi: 10.1128/iai.28.2.620-623.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zweig M., Heilman C. J., Jr, Rabin H., Hopkins R. F., 3rd, Neubauer R. H., Hampar B. Production of monoclonal antibodies against nucleocapsid proteins of herpes simplex virus types 1 and 2. J Virol. 1979 Nov;32(2):676–678. doi: 10.1128/jvi.32.2.676-678.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]