{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T05:22:36Z","timestamp":1774502556861,"version":"3.50.1"},"reference-count":55,"publisher":"American Society for Microbiology","issue":"21","license":[{"start":{"date-parts":[[2011,11,1]],"date-time":"2011-11-01T00:00:00Z","timestamp":1320105600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2011,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Ectromelia virus (ECTV) is a natural pathogen of mice that causes mousepox, and many of its genes have been implicated in the modulation of host immune responses. Serine protease inhibitor 2 (SPI-2) is one of these putative ECTV host response modifier proteins. SPI-2 is conserved across orthopoxviruses, but results defining its mechanism of action and<jats:italic>in vivo<\/jats:italic>function are lacking or contradictory. We studied the role of SPI-2 in mousepox by deleting the<jats:italic>SPI-2<\/jats:italic>gene or its serine protease inhibitor reactive site. We found that SPI-2 does not affect viral replication or cell-intrinsic apoptosis pathways, since mutant viruses replicate<jats:italic>in vitro<\/jats:italic>as efficiently as wild-type virus. However, in the absence of SPI-2 protein, ECTV is attenuated in mousepox-susceptible mice, resulting in lower viral loads in the liver, decreased spleen pathology, and substantially improved host survival. This attenuation correlates with more effective immune responses in the absence of SPI-2, including an earlier serum gamma interferon (IFN-\u03b3) response, raised serum interleukin 18 (IL-18), increased numbers of granzyme B<jats:sup>+<\/jats:sup>CD8<jats:sup>+<\/jats:sup>T cells, and, most notably, increased numbers and activation of NK cells. Both virus attenuation and the improved immune responses associated with SPI-2 deletion from ECTV are lost when mice are depleted of NK cells. Consequently, SPI-2 renders mousepox lethal in susceptible strains by preventing protective NK cell defenses.<\/jats:p>","DOI":"10.1128\/jvi.00256-11","type":"journal-article","created":{"date-parts":[[2011,8,18]],"date-time":"2011-08-18T00:59:43Z","timestamp":1313629183000},"page":"11170-11182","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":18,"title":["The Ectromelia Virus SPI-2 Protein Causes Lethal Mousepox by Preventing NK Cell Responses"],"prefix":"10.1128","volume":"85","author":[{"given":"Carolina R.","family":"Melo-Silva","sequence":"first","affiliation":[{"name":"Department of Emerging Pathogens and Vaccines, John Curtin School of Medical Research, Australian National University, Canberra ACT, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David C.","family":"Tscharke","sequence":"additional","affiliation":[{"name":"Division of Biomedical Research and Biochemistry, Research School of Biology, Australian National University, Canberra ACT, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mario","family":"Lobigs","sequence":"additional","affiliation":[{"name":"Department of Emerging Pathogens and Vaccines, John Curtin School of Medical Research, Australian National University, Canberra ACT, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aulikki","family":"Koskinen","sequence":"additional","affiliation":[{"name":"Department of Emerging Pathogens and Vaccines, John Curtin School of Medical Research, Australian National University, Canberra ACT, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yik Chun","family":"Wong","sequence":"additional","affiliation":[{"name":"Division of Biomedical Research and Biochemistry, Research School of Biology, Australian National University, Canberra ACT, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R. Mark","family":"Buller","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Saint Louis University Health Sciences Center, Saint Louis, Missouri"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arno","family":"M\u00fcllbacher","sequence":"additional","affiliation":[{"name":"Department of Emerging Pathogens and Vaccines, John Curtin School of Medical Research, Australian National University, Canberra ACT, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthias","family":"Regner","sequence":"additional","affiliation":[{"name":"Department of Emerging Pathogens and Vaccines, John Curtin School of Medical Research, Australian National University, Canberra ACT, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-83-8-1965"},{"key":"e_1_3_3_3_2","volume-title":"Immunology of virus diseases","author":"Blanden R. V.","year":"1989","unstructured":"BlandenR. V.. 1989. Immunology of virus diseases. Brolga Press, Curtin, Australia."},{"key":"e_1_3_3_4_2","first-page":"56","article-title":"T cell response to viral and bacterial infection","volume":"19","author":"Blanden R. V","year":"1974","unstructured":"BlandenR. V. 1974. T cell response to viral and bacterial infection. Transplant Rev. 19:56\u201388.","journal-title":"Transplant Rev."},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.164.6.3246"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0402949101"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0042-6822(03)00520-8"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/0042-6822(92)90445-U"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.icb.7100062"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.69.9.5875-5877.1995"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.021908.132612"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.70.9.6479-6485.1996"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.62.6.1849-1854.1988"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.64.6.3108-3111.1990"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.0040030"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20100282"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2007.04.010"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.70.4.2208-2214.1996"},{"key":"e_1_3_3_19_2","volume-title":"Mousepox","author":"Fenner F.","year":"1997","unstructured":"FennerF. BullerR. M. L.. 1997. Mousepox. Lippincott-Raven Publishers, Philadelphia, PA."},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200939988"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0903759"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01313742"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-2427(98)00086-5"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.67.7.4214-4226.1993"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-78-3-677"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0042-6822(95)80028-X"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/0008-8749(86)90311-4"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)32171-3"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.78.6.2770-2779.2004"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00237-9"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2008.10.041"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.72.10.7830-7839.1998"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2008.08.014"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1002\/rmv.381"},{"key":"e_1_3_3_35_2","doi-asserted-by":"crossref","first-page":"1765","DOI":"10.4049\/jimmunol.147.6.1765","article-title":"Alloreactive cytotoxic T cells recognize MHC class I antigen without peptide specificity","volume":"147","author":"M\u00fcllbacher A.","year":"1991","unstructured":"M\u00fcllbacherA.. 1991. Alloreactive cytotoxic T cells recognize MHC class I antigen without peptide specificity. J. Immunol. 147:1765\u20131772.","journal-title":"J. Immunol."},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.73.2.1665-1667.1999"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2004.08.004"},{"key":"e_1_3_3_38_2","doi-asserted-by":"crossref","first-page":"7315","DOI":"10.4049\/jimmunol.162.12.7315","article-title":"Poxvirus-encoded serpins do not prevent cytolytic T cell-mediated recovery from primary infections","volume":"162","author":"M\u00fcllbacher A.","year":"1999","unstructured":"M\u00fcllbacherA. WallichR. MoyerR. W. SimonM. M.. 1999. Poxvirus-encoded serpins do not prevent cytolytic T cell-mediated recovery from primary infections. J. Immunol. 162:7315\u20137321.","journal-title":"J. Immunol."},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.24.13950"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.79905-0"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1038\/378088a0"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/0042-6822(89)90128-1"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0007512"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02061-06"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.18.10377"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(92)90223-Y"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.186.9.1591"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1994.1014"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.74.18.8460-8471.2000"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-83-8-1977"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-81-10-2425"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1089\/08828240151061428"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0803985"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jviromet.2010.11.003"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20071854"},{"key":"e_1_3_3_56_2","first-page":"1953","article-title":"Influenza-associated encephalopathy\u2014pathophysiology and disease mechanisms","volume":"61","author":"Yokota S","year":"2003","unstructured":"YokotaS. 2003. Influenza-associated encephalopathy\u2014pathophysiology and disease mechanisms. Nippon Rinsho 61:1953\u20131958.","journal-title":"Nippon Rinsho"}],"container-title":["Journal of Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.00256-11","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.00256-11","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,10]],"date-time":"2024-04-10T07:43:11Z","timestamp":1712734991000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/JVI.00256-11"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,11]]},"references-count":55,"journal-issue":{"issue":"21","published-print":{"date-parts":[[2011,11]]}},"alternative-id":["10.1128\/JVI.00256-11"],"URL":"https:\/\/doi.org\/10.1128\/jvi.00256-11","relation":{},"ISSN":["0022-538X","1098-5514"],"issn-type":[{"value":"0022-538X","type":"print"},{"value":"1098-5514","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,11]]},"assertion":[{"value":"2011-02-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2011-08-08","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2011-10-06","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}