A Novel Block to Mouse Mammary Tumor Virus Infection of Lymphocytes in B10.BR Mice

Department of Microbiology and Abramson Family Cancer Center, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
Journal of Virology (Impact Factor: 4.44). 03/2008; 82(3):1314-22. DOI: 10.1128/JVI.01848-07
Source: PubMed


Classic studies on C57BL-derived mouse strains showed that they were resistant to mouse mammary tumor virus (MMTV) infection. Although one form of resistance mapped to the major histocompatibility complex (MHC) locus, at least one other, unknown gene was implicated in this resistance. We show here that B10.BR mice, which are derived from C57BL mice but have the same MHC locus (H-2(k)) as susceptible C3H/HeN mice, are resistant to MMTV, and show a lack of virus spread in their lymphoid compartments but not their mammary epithelial cells. Although in vivo virus superantigen (Sag)-mediated activation of T cells was similar in C3H/HeN and B10.BR mice, T cell-dependent B-cell and dendritic cell activation was diminished in the latter. Ex vivo, B10.BR T cells showed a diminished capacity to proliferate in response to the MMTV Sag. The genetic segregation of the resistance phenotype indicated that it maps to a single allele. These data highlight the role of Sag-dependent T-cell responses in MMTV infection and point to a novel mechanism for the resistance of mice to retroviral infection that could lead to a better understanding of the interplay between hosts and pathogens.

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    • "Fluorescence activated cell sorting ( FACS ) FACS analysis was conducted as previously described ( Okeoma et al . , 2008 ) . Briefly , approximately 5 Â 10 5 cells were incubated with anti BST - 2 or relevant IgG antibodies for 30 min on ice . Cells were washed in PBSþ1% bovine serum albumin ( Sigma - Aldrich ) then fixed with 2% paraformaldehyde . In some experiments , yfp expression was evaluated in place of BST - 2 . At least 10 , 000 events were colle"
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    ABSTRACT: Chikungunya virus (CHIKV) is a re-emerging alphavirus transmitted by Aedes mosquitoes. Infection with CHIKV elicits a type I interferon response that facilities virus clearance, probably through the action of down-stream effectors such as antiviral IFN-stimulated genes (ISGs). Bone marrow stromal antigen 2 (BST-2) is an ISG shown to restrict HIV-1 replication by preventing the infection of bystander cells by tethering progeny virions on the surface of infected cells. Here we show that enrichment of cell surface BST-2 results in retention of CHIKV virus like particles (VLPs) on the cell membrane. BST-2 was found to co-localize with CHIKV structural protein E1 in the context of VLPs without any noticeable effect on BST-2 level. However, CHIKV nonstructural protein 1 (nsP1) overcomes BST-2-mediated VLPs tethering by down-regulating BST-2 expression. We conclude that BST-2 tethers CHIKV VLPs on the host cell plasma membrane and identify CHIKV nsP1 as a novel BST-2 antagonist.
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    • "The percentage of CD4+ T cells expressing CD69 increased from 2.78%/2.44% in naïve WT/mA3-/- mice to 12.70%, 13.9%, and 21.0% in infected WT, mA3+/-, and mA3-/- mice respectively (Figure 3H). The expansion of CD69 expressing B220+ and CD4+ T cells has been previously reported in mice chronically infected with the LP-BM5 related retroviruses, Friend MLV [66] and MMTV [67]. "
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    Retrovirology 06/2012; 9(1):50. DOI:10.1186/1742-4690-9-50 · 4.19 Impact Factor
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    • "For cDNA synthesis, equivalent amounts of RNA treated with DNase I (Qiagen, Inc.) were reverse-transcribed with high capacity cDNA reverse transcription Kit (Applied Biosystems, ABI), and the cDNA was amplified with primers specific to BST-2, MMTV.Mm5MT, IFNα, IFNβ, 2'-5'-OAS, and GAPDH. DNA was used to quantitatively detect integrated proviruses [32,33], using primers specific to the MMTV long terminal repeats and puromycin. Semi-quantitative PCR was performed using Veriti 96-Well Thermal Cycler, and real time qPCR was carried out using ABI 7500 FAST thermal cycler (ABI). "
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