Disease relevance of Rnf7

• Mouse mammary tumor virus (MMTV) encodes a superantigen (Sag) that is required for efficient milk-borne transmission of virus from mothers to offspring [1].
• Mice injected with wild-type provirus showed Sag activity by the deletion of Sag-specific T cells and induction of mammary tumors in 100% of injected animals [1].
• Elevated expression of SAG/ROC2/Rbx2/Hrt2 in human colon carcinomas: SAG does not induce neoplastic transformation, but antisense SAG transfection inhibits tumor cell growth [2].

High impact information on Rnf7

• APCs from the mutant mice failed to present v-Sag, as determined by the lack of Sag-specific T cell activation, Sag-induced T cell deletion, and by the aborted MMTV infection [3].
• Although at low levels of ligand expression in the thymus some signs of activation were observed in immature thymocytes, we were unable to detect a level of Sag expression that led to net positive selection [4].
• Yeast homolog of human SAG/ROC2/Rbx2/Hrt2 is essential for cell growth, but not for germination: chip profiling implicates its role in cell cycle regulation [5].
• The mRNA used for Sag expression is controversial, and at least four different promoters (two in the long terminal repeat and two in the envelope gene) for sag mRNA have been reported [1].
• Third-litter offspring of mice injected with wild-type provirus showed Sag-specific T-cell deletion and developed mammary tumors with kinetics similar to those for mice infected by nursing on MMTV-infected mothers, whereas the third-litter offspring of the splice donor mutant-injected mice did not [1].

Biological context of Rnf7

• We show here, using MMTV(SIM), a viral isolate which requires major histocompatibility complex class II I-E expression to induce a strong Sag response in vivo, that transgenic mice expressing I-E exclusively on DCs (I-EalphaDC tg) reveal a strong Sag response [6].
• Intracellular and cell surface staining of the panel of mutants indicated that any decrease in glycosylation resulted in reduced levels of intracellular protein and undetectable surface expression, suggesting that decreased glycosylation leads to rapid Sag degradation and abates trafficking to the plasma membrane [7].
• Taken together, these data support the previous finding that Naf and Sag have separable activities and suggest that Naf may play a role in modulating host cell gene expression during MMTV infection [8].
• The open reading frame (ORF) in the long terminal repeat (LTR) of mouse mammary tumor virus (MMTV) has recently been shown to encode multiple products including a negative acting factor (Naf) and a superantigen (Sag) [9].

Anatomical context of Rnf7

• Our results indicate that after priming by DCs in the context of I-E, the MMTV(SIM) Sag can be recognized on the surface of B cells in the context of I-A [6].
• Despite the lack of Sag activity, many of the sag mutant viruses were capable of sporadic infections of the mammary glands of injected mice but not of offspring mice, indicating that functional Sag increases the probability of milk-borne MMTV infection [10].
• Recognition of Sag by particular TCRs results in T-cell stimulation, release of cytokines, and amplification of MMTV infection in lymphoid cells that are needed for infection of adolescent mammary tissue [10].
• Furthermore, we show that infection of purified B cells with MMTV induces entry of Sag-responsive T cells into the cell cycle, while other professional antigen-presenting cells, such as dendritic cells, are much less efficient in inducing a response [11].
• The transmission of milk-borne or exogenous mouse mammary tumor virus (MMTV) requires infection of B cells in the gut-associated lymphoid tissue and expression of the superantigen (Sag) protein at the B-cell surface [12].

Analytical, diagnostic and therapeutic context of Rnf7

• Such a model would allow the dissection of the early phase of infection, the assessment of the contributions of different cell types, and the screening of large panels of molecules for their potential roles in infection and Sag response [11].
• The RT-PCR assay for sag mRNA appears to measure the Sag-induced stimulation previously predicted for milk-borne MMTV infection [13].

References