{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T17:06:13Z","timestamp":1791219973892,"version":"4.1.0"},"reference-count":63,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2001,3,1]],"date-time":"2001-03-01T00:00:00Z","timestamp":983404800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2001,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Whether or not NO plays a critical role in murine CMV (MCMV) infection has yet to be elucidated. In this study, we examined the role of NO in acute infection with MCMV using NO synthase type 2 (NOS2)-deficient mice. NOS2\u2212\/\u2212 mice were more susceptible to lethal infection with MCMV than NOS2+\/+ mice and generated a much higher peak virus titer in the salivary gland after acute infection. A moderate increase in the MCMV titer was also observed in other organs of NOS2\u2212\/\u2212 mice such as the spleen, lung, and liver. The immune responses to MCMV infection including NK cell cytotoxicity and CTL response in NOS2\u2212\/\u2212 mice were comparable with those of NOS2+\/+ mice. Moreover, the ability to produce IFN-\u03b3 is not impaired in NOS2\u2212\/\u2212 mice after MCMV infection. The peritoneal macrophages from NOS2\u2212\/\u2212 mice, however, exhibited a lower antiviral activity than those from NOS2+\/+ mice, resulting in an enhanced viral replication in macrophages themselves. Treatment of these cells from NOS2+\/+ mice with a selective NOS2 inhibitor decreased the antiviral activity to a level below that obtained with NOS2\u2212\/\u2212 mice. In addition, the absence of NOS2 and NOS2-mediated antiviral activity of macrophages resulted in not only an enhanced MCMV replication and a high mortality but also a consequent risk of the latency. It was thus concluded that the NOS2-mediated antiviral activity of macrophages via NO plays a protective role against MCMV infection at an early and late stage of the infection.<\/jats:p>","DOI":"10.4049\/jimmunol.166.5.3533","type":"journal-article","created":{"date-parts":[[2014,4,20]],"date-time":"2014-04-20T23:20:12Z","timestamp":1398036012000},"page":"3533-3541","source":"Crossref","is-referenced-by-count":49,"title":["Role of Nitric Oxide Synthase Type 2 in Acute Infection with Murine Cytomegalovirus"],"prefix":"10.1093","volume":"166","author":[{"given":"Satoshi","family":"Noda","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, Tokai University School of Medicine , Isehara, Kanagawa ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuo","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Tokai University School of Medicine , Isehara, Kanagawa ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sada-aki","family":"Sawamura","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Tokai University School of Medicine , Isehara, Kanagawa ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masafumi","family":"Sasaki","sequence":"additional","affiliation":[{"name":"Department of Virology, Medical Institute of Bioregulation, Kyushu University , Fukuoka ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takako","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Tokai University School of Medicine , Isehara, Kanagawa ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsunaka","family":"Mikami","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Tokai University School of Medicine , Isehara, Kanagawa ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuji","family":"Aiba","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Tokai University School of Medicine , Isehara, Kanagawa ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideaki","family":"Hasegawa","sequence":"additional","affiliation":[{"name":"Cell Biology Research Laboratory, Tokai University School of Medicine , Isehara, Kanagawa ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noboru","family":"Kawabe","sequence":"additional","affiliation":[{"name":"Cell Biology Research Laboratory, Tokai University School of Medicine , Isehara, Kanagawa ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhiro","family":"Koga","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Tokai University School of Medicine , Isehara, Kanagawa ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2001,3,1]]},"reference":[{"key":"2026020208045918000_R1","first-page":"1","volume-title":"Arch. 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