| Virus Name | Murine gammaherpesvirus 68 |
| Virus Short Name | MHV-68 |
| Order | Herpesvirales |
| Virus Family | Herpesviridae |
| Virus Subfamily | Gammaherpesvirinae |
| Genus | Rhadinovirus |
| Species | Murid herpesvirus 68 |
| Host | Murine,mammals |
| Cell Tropism | B lymphocytes |
| Associated Disease | Mononucleosis, associated with environemental diseases: burkitt?s lymphoma nasopharyngeal carcinoma (npc) |
| Mode of Transmission | Contact, saliva |
| VIPR DB link | http://www.viprbrc.org/brc/vipr_allSpecies_search.do?method=SubmitForm&decorator=herpes |
| ICTV DB link | https://talk.ictvonline.org/ictv-reports/ictv_9th_report/dsdna-viruses-2011/w/dsdna_viruses/91/herpesviridae |
| Virus Host DB link | http://www.genome.jp/virushostdb/view/?virus_lineage=Herpesviridae |
| Paper Title | Inhibition of NF-?B activation In vivo impairs establishment of gammaherpesvirus latency |
| Author's Name | Laurie T. Krug, Janice M. Moser, Shelley M. Dickerson, Samuel H. Speck |
| Journal Name | PLOS Pathogens |
| Pubmed ID | 17257062 |
| Abstract | A critical determinant in chronic gammaherpesvirus infections is the ability of these viruses to establish latency in a lymphocyte reservoir. The nuclear factor (NF)-kappaB family of transcription factors represent key players in B-cell biology and are targeted by gammaherpesviruses to promote host cell survival, proliferation, and transformation. However, the role of NF-kappaB signaling in the establishment of latency in vivo has not been addressed. Here we report the generation and in vivo characterization of a recombinant murine gammaherpesvirus 68 (gammaHV68) that expresses a constitutively active form of the NF-kappaB inhibitor, IkappaBalphaM. Inhibition of NF-kappaB signaling upon infection with gammaHV68-IkappaBalphaM did not affect lytic replication in cell culture or in the lung following intranasal inoculation. However, there was a substantial decrease in the frequency of latently infected lymphocytes in the lung (90% reduction) and spleens (97% reduction) 16 d post intranasal inoculation. Importantly, the defect in establishment of latency in lung B cells could not be overcome by increasing the dose of virus 100-fold. The observed decrease in establishment of viral latency correlated with a loss of activated, CD69(hi) B cells in both the lungs and spleen at day 16 postinfection, which was not apparent by 6 wk postinfection. Constitutive expression of Bcl-2 in B cells did not rescue the defect in the establishment of latency observed with gammaHV68-IkappaBalphaM, indicating that NF-kappaB-mediated functions apart from Bcl-2-mediated B-cell survival are critical for the efficient establishment of gammaherpesvirus latency in vivo. In contrast to the results obtained following intranasal inoculation, infection of mice with gammaHV68-IkappaBalphaM by the intraperitoneal route had only a modest impact on splenic latency, suggesting that route of inoculation may alter requirements for establishment of virus latency in B cells. Finally, analyses of the pathogenesis of gammaHV68-IkappaBalphaM provides evidence that NF-kappaB signaling plays an important role during multiple stages of gammaHV68 infection in vivo and, as such, represents a key host regulatory pathway that is likely manipulated by the virus to establish latency in B cells. |
| Used Model | C57BL/6 and C57BL/6 mice |
| DOI | 10.1371/journal.ppat.0030011 |
