Cytokine-Mediated Survival from Lethal Herpes Simplex Virus Infection: Role of Programmed Neuronal Death
The mechanisms responsible for cytokine-mediated antiviral effects are not fully understood. We approached this problem by studying the outcome of intraocular herpes simplex (HSV) infection in transgenic mice that express interferon γ in the photoreceptor cells of the retina. These transgenic mice s...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 1995-04, Vol.92 (8), p.3411-3415 |
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| container_title | Proceedings of the National Academy of Sciences - PNAS |
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| creator | Geiger, Kathrin D. Gurushanthaiah, Deepak Howes, Edward L. Lewandowski, Gail A. Reed, John C. Bloom, Floyd E. Sarvetnick, Nora E. |
| description | The mechanisms responsible for cytokine-mediated antiviral effects are not fully understood. We approached this problem by studying the outcome of intraocular herpes simplex (HSV) infection in transgenic mice that express interferon γ in the photoreceptor cells of the retina. These transgenic mice showed selective survival from lethal HSV-2 infection manifested in both eyes, the optic nerve, and the brain. Although transgenic mice developed greater inflammatory responses to the virus in the eyes, inflammation and viral titers in their brains were equivalent to nontransgenic mice. However, survival of transgenic mice correlated with markedly lower numbers of central neurons undergoing apoptosis. The protooncogene Bcl2 was found to be induced in the HSV-2-infected brains of transgenic mice, allowing us to speculate on its role in fostering neuronal survival in this model. These observations imply a complex interaction between cytokine, virus, and host cellular factors. Our results suggest a cytokine-regulated salvage pathway that allows for survival of infected neurons. |
| doi_str_mv | 10.1073/pnas.92.8.3411 |
| format | Article |
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We approached this problem by studying the outcome of intraocular herpes simplex (HSV) infection in transgenic mice that express interferon γ in the photoreceptor cells of the retina. These transgenic mice showed selective survival from lethal HSV-2 infection manifested in both eyes, the optic nerve, and the brain. Although transgenic mice developed greater inflammatory responses to the virus in the eyes, inflammation and viral titers in their brains were equivalent to nontransgenic mice. However, survival of transgenic mice correlated with markedly lower numbers of central neurons undergoing apoptosis. The protooncogene Bcl2 was found to be induced in the HSV-2-infected brains of transgenic mice, allowing us to speculate on its role in fostering neuronal survival in this model. These observations imply a complex interaction between cytokine, virus, and host cellular factors. Our results suggest a cytokine-regulated salvage pathway that allows for survival of infected neurons.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.92.8.3411</identifier><identifier>PMID: 7724576</identifier><language>eng</language><publisher>United States: National Academy of Sciences of the United States of America</publisher><subject>Animals ; Antigens, CD ; Apoptosis ; Brain ; Brain - pathology ; Cellular biology ; Eye - cytology ; Eye - immunology ; Eye Infections, Viral ; Eyes ; Herpes Simplex - drug therapy ; Herpes Simplex - genetics ; Herpes Simplex - mortality ; Herpes viruses ; Herpesvirus 1, Human - pathogenicity ; Herpesvirus 2, Human - pathogenicity ; Human herpesvirus 1 ; Human herpesvirus 2 ; Immunity (Disease) ; Immunohistochemistry ; Infections ; Interferon-gamma - genetics ; Interferon-gamma - therapeutic use ; Mice ; Mice, Inbred BALB C ; Mice, Transgenic ; Neurons ; Neurons - pathology ; Proto-Oncogene Proteins - biosynthesis ; Proto-Oncogene Proteins - genetics ; Proto-Oncogene Proteins c-bcl-2 ; Retina - virology ; Survival Analysis ; Transgenic animals ; Up-Regulation ; Vero cells ; Viruses</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 1995-04, Vol.92 (8), p.3411-3415</ispartof><rights>Copyright 1995 The National Academy of Sciences of the United States of America</rights><rights>Copyright National Academy of Sciences Apr 11, 1995</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c484t-e068b11155b8ca1adc97835e3bfd4fbe0736c6c8c5312afacc37ff8b023355c73</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/92/8.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/2367076$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/2367076$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,315,728,781,785,804,886,27929,27930,53796,53798,58022,58255</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/7724576$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Geiger, Kathrin D.</creatorcontrib><creatorcontrib>Gurushanthaiah, Deepak</creatorcontrib><creatorcontrib>Howes, Edward L.</creatorcontrib><creatorcontrib>Lewandowski, Gail A.</creatorcontrib><creatorcontrib>Reed, John C.</creatorcontrib><creatorcontrib>Bloom, Floyd E.</creatorcontrib><creatorcontrib>Sarvetnick, Nora E.</creatorcontrib><title>Cytokine-Mediated Survival from Lethal Herpes Simplex Virus Infection: Role of Programmed Neuronal Death</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>The mechanisms responsible for cytokine-mediated antiviral effects are not fully understood. We approached this problem by studying the outcome of intraocular herpes simplex (HSV) infection in transgenic mice that express interferon γ in the photoreceptor cells of the retina. These transgenic mice showed selective survival from lethal HSV-2 infection manifested in both eyes, the optic nerve, and the brain. Although transgenic mice developed greater inflammatory responses to the virus in the eyes, inflammation and viral titers in their brains were equivalent to nontransgenic mice. However, survival of transgenic mice correlated with markedly lower numbers of central neurons undergoing apoptosis. The protooncogene Bcl2 was found to be induced in the HSV-2-infected brains of transgenic mice, allowing us to speculate on its role in fostering neuronal survival in this model. These observations imply a complex interaction between cytokine, virus, and host cellular factors. Our results suggest a cytokine-regulated salvage pathway that allows for survival of infected neurons.</description><subject>Animals</subject><subject>Antigens, CD</subject><subject>Apoptosis</subject><subject>Brain</subject><subject>Brain - pathology</subject><subject>Cellular biology</subject><subject>Eye - cytology</subject><subject>Eye - immunology</subject><subject>Eye Infections, Viral</subject><subject>Eyes</subject><subject>Herpes Simplex - drug therapy</subject><subject>Herpes Simplex - genetics</subject><subject>Herpes Simplex - mortality</subject><subject>Herpes viruses</subject><subject>Herpesvirus 1, Human - pathogenicity</subject><subject>Herpesvirus 2, Human - pathogenicity</subject><subject>Human herpesvirus 1</subject><subject>Human herpesvirus 2</subject><subject>Immunity (Disease)</subject><subject>Immunohistochemistry</subject><subject>Infections</subject><subject>Interferon-gamma - genetics</subject><subject>Interferon-gamma - therapeutic use</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Transgenic</subject><subject>Neurons</subject><subject>Neurons - pathology</subject><subject>Proto-Oncogene Proteins - biosynthesis</subject><subject>Proto-Oncogene Proteins - genetics</subject><subject>Proto-Oncogene Proteins c-bcl-2</subject><subject>Retina - virology</subject><subject>Survival Analysis</subject><subject>Transgenic animals</subject><subject>Up-Regulation</subject><subject>Vero cells</subject><subject>Viruses</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1995</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kUuP0zAUhS0EGsrAlhVIEYvZpfiV2EFsUHnMSOUhBthajns9dUniYDvVzL_HVUtVWLCypfOd63N9EHpK8JxgwV6Og47zhs7lnHFC7qEZwQ0pa97g-2iGMRWl5JQ_RI9i3GCMm0riM3QmBOWVqGdovbhL_qcboPwIK6cTrIrrKWzdVneFDb4vlpDW-X4JYYRYXLt-7OC2-OHCFIurwYJJzg-viq--g8Lb4kvwN0H3fZ7zCabgh-x9CzqtH6MHVncRnhzOc_T9_btvi8ty-fnD1eLNsjRc8lQCrmVLCKmqVhpN9Mo0QrIKWGtX3LaQV65NbaSpGKHaamOYsFa2mDJWVUawc_R6P3ec2pzCwJCC7tQYXK_DnfLaqb-Vwa3Vjd8qTomos_3iYA_-1wQxqd5FA12nB_BTVPnjaEU5z-CLf8CNn0JeNyqKCW1q0bAMzfeQCT7GAPaYg2C1q0_t6lMNVVLt6suG56fpj_ihrxN95_ujnvov_qcrO3VdgtuUwWd7cBOTD0eSslrg_M5vVHm5Og</recordid><startdate>19950411</startdate><enddate>19950411</enddate><creator>Geiger, Kathrin D.</creator><creator>Gurushanthaiah, Deepak</creator><creator>Howes, Edward L.</creator><creator>Lewandowski, Gail A.</creator><creator>Reed, John C.</creator><creator>Bloom, Floyd E.</creator><creator>Sarvetnick, Nora E.</creator><general>National Academy of Sciences of the United States of America</general><general>National Acad Sciences</general><general>National Academy of Sciences</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>19950411</creationdate><title>Cytokine-Mediated Survival from Lethal Herpes Simplex Virus Infection: Role of Programmed Neuronal Death</title><author>Geiger, Kathrin D. ; 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We approached this problem by studying the outcome of intraocular herpes simplex (HSV) infection in transgenic mice that express interferon γ in the photoreceptor cells of the retina. These transgenic mice showed selective survival from lethal HSV-2 infection manifested in both eyes, the optic nerve, and the brain. Although transgenic mice developed greater inflammatory responses to the virus in the eyes, inflammation and viral titers in their brains were equivalent to nontransgenic mice. However, survival of transgenic mice correlated with markedly lower numbers of central neurons undergoing apoptosis. The protooncogene Bcl2 was found to be induced in the HSV-2-infected brains of transgenic mice, allowing us to speculate on its role in fostering neuronal survival in this model. These observations imply a complex interaction between cytokine, virus, and host cellular factors. Our results suggest a cytokine-regulated salvage pathway that allows for survival of infected neurons.</abstract><cop>United States</cop><pub>National Academy of Sciences of the United States of America</pub><pmid>7724576</pmid><doi>10.1073/pnas.92.8.3411</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Proceedings of the National Academy of Sciences - PNAS, 1995-04, Vol.92 (8), p.3411-3415 |
| issn | 0027-8424 1091-6490 |
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| source | MEDLINE; JSTOR Archive Collection A-Z Listing; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | Animals Antigens, CD Apoptosis Brain Brain - pathology Cellular biology Eye - cytology Eye - immunology Eye Infections, Viral Eyes Herpes Simplex - drug therapy Herpes Simplex - genetics Herpes Simplex - mortality Herpes viruses Herpesvirus 1, Human - pathogenicity Herpesvirus 2, Human - pathogenicity Human herpesvirus 1 Human herpesvirus 2 Immunity (Disease) Immunohistochemistry Infections Interferon-gamma - genetics Interferon-gamma - therapeutic use Mice Mice, Inbred BALB C Mice, Transgenic Neurons Neurons - pathology Proto-Oncogene Proteins - biosynthesis Proto-Oncogene Proteins - genetics Proto-Oncogene Proteins c-bcl-2 Retina - virology Survival Analysis Transgenic animals Up-Regulation Vero cells Viruses |
| title | Cytokine-Mediated Survival from Lethal Herpes Simplex Virus Infection: Role of Programmed Neuronal Death |
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