scholarly journals Mouse Mammary Tumor Virus Superantigen Expression in B Cells Is Regulated by a Central Enhancer within the pol Gene

1998 ◽  
Vol 72 (7) ◽  
pp. 6073-6082 ◽  
Author(s):  
Frank U. Reuss ◽  
John M. Coffin
Keyword(s):  
Gene Expression ◽  
B Cells ◽  
B Cell ◽  
Mammary Tumor ◽  
Mouse Mammary Tumor Virus ◽  
Luciferase Reporter ◽  
B Cell Lymphomas ◽  
Mammary Tumor Virus ◽  
Mouse Mammary Tumor ◽  
Tumor Virus

ABSTRACT Expression of mouse mammary tumor virus (MMTV)-encoded superantigens in B lymphocytes is required for viral transmission and pathogenesis. The mechanism of superantigen expression from the viralsag gene in B cells is largely unknown, due to problems with detection and quantification of these low-abundance proteins. We have established a sensitive superantigen-luciferase reporter assay to study the expression and regulation of the MMTV sag gene in B-cell lymphomas. The regulatory elements for retroviral gene expression are generally located in the 5′ long terminal repeat (LTR) of the provirus. However, we found that neither promoters nor enhancers in the MMTV 5′ LTR play a significant role in superantigen expression in these cells. Instead, the essential regulatory regions are located in the pol and env genes of MMTV. We report here that maximal sag expression in B-cell lines depends on an enhancer within the viral pol gene which can be localized to a minimal 183-bp region. Regulation of saggene expression differs between B-cell lymphomas and pro-B cells, where an enhancer within the viral LTRs is involved. Thus, MMTVsag expression during B-cell development is achieved through the use of two separate enhancer elements.

Posttranscriptional regulation of cellular gene expression by the c-myc oncogene

1989 ◽  
Vol 9 (1) ◽  
pp. 124-134
Author(s):  
G C Prendergast ◽  
M D Cole
Keyword(s):  
Gene Expression ◽  
Cell Lines ◽  
Mammary Tumor ◽  
Mouse Mammary Tumor Virus ◽  
Cellular Gene ◽  
Mammary Tumor Virus ◽  
Myc Oncogene ◽  
Mouse Mammary Tumor ◽  
Tumor Virus ◽  
Myc Gene

The c-myc oncogene has been implicated in the development of many different cancers, yet the mechanism by which the c-myc protein alters cellular growth control has proven elusive. We used a cDNA hybridization difference assay to isolate two genes, mr1 and mr2, that were constitutively expressed (i.e., deregulated) in rodent fibroblast cell lines immortalized by transfection of a viral promoter-linked c-myc gene. Both cDNAs were serum inducible in quiescent G0 fibroblasts, suggesting that they are functionally related to cellular proliferative processes. Although there were significant differences in cytoplasmic mRNA levels between myc-immortalized and control cells, the rates of transcription and mRNA turnover of both genes were similar, suggesting that c-myc regulates mr1 and mr2 expression by some nuclear posttranscriptional mechanism. mr1 was also rapidly (within 2 h) and specifically induced by dexamethasone in BALB/c cell lines expressing a mouse mammary tumor virus long terminal repeat-driven myc gene, under conditions where other growth factor-inducible genes were unaffected. A frameshift mutation in the mouse mammary tumor virus myc gene destroyed the dexamethasone stimulation of mr1, indicating that c-myc protein is required for the effect. As in the myc-immortalized cells, the induction of mr1 by c-myc occurred without detectable changes in mr1 transcription or cytoplasmic mRNA stability, implicating regulation, either direct or indirect, through a nuclear posttranscriptional mechanism. These results provide evidence that c-myc can rapidly modulate cellular gene expression and suggest that c-myc may function in gene regulation at the level of RNA export, splicing, or nuclear RNA turnover.

scholarly journals Reverse transcriptase-dependent and -independent phases of infection with mouse mammary tumor virus: implications for superantigen function.

1994 ◽  
Vol 180 (6) ◽  
pp. 2347-2351 ◽  
Author(s):  
W Held ◽  
G A Waanders ◽  
H Acha-Orbea ◽  
H R MacDonald
Keyword(s):  
Immune Response ◽  
T Cells ◽  
B Cells ◽  
Mammary Tumor ◽  
Mouse Mammary Tumor Virus ◽  
Clonal Expansion ◽  
Local Immune Response ◽  
Mammary Tumor Virus ◽  
Mouse Mammary Tumor ◽  
Tumor Virus

Mouse mammary tumor virus (MMTV) encodes a superantigen (SAg) that promotes stable infection and virus transmission. Upon subcutaneous MMTV injection, infected B cells present SAg to SAg-reactive T cells leading to a strong local immune response in the draining lymph node (LN) that peaks after 6 d. We have used the reverse transcriptase inhibitor 3'-azido-3'-deoxythymidine (AZT) to dissect in more detail the mechanism of SAg-dependent enhancement of MMTV infection in this system. Our data show that no detectable B or T cell response to SAg occurs in AZT pretreated mice. However, if AZT treatment is delayed 1-2 d after MMTV injection, a normal SAg-dependent local immune response is observed on day 6. Quantitation of viral DNA in draining LN of these infected mice indicates that a 4,000-fold increase in the absolute numbers of infected cells occurs between days 2 and 6 despite the presence of AZT. Furthermore MMTV DNA was found preferentially in surface IgG+ B cells of infected mice and was not detectable in SAg-reactive T cells. Collectively our data suggest that MMTV infection occurs preferentially in B cells without SAg involvement and is completed 1-2 d after virus challenge. Subsequent amplification of MMTV infection between days 2 and 6 requires SAg expression and occurs in the absence of any further requirement for reverse transcription. We therefore conclude that clonal expansion of infected B cells via cognate interaction with SAg-reactive T cells is the predominant mechanism for increasing the level of MMTV infection. Since infected B cells display a memory (surface IgG+) phenotype, both clonal expansion and possibly longevity of the virus carrier cells may contribute to stable MMTV infection.

Detection of Retroviral Superantigen and Products of the Envelope Gene from Endogenous Mouse Mammary Tumor Virus in B Cells from BALB/c Mice

1995 ◽  
Vol 163 (2) ◽  
pp. 191-197 ◽  
Author(s):  
Mayra Lopez-Cepero ◽  
Yang Wang ◽  
Iafa Keydar ◽  
Carolyn Brandt-Carlson ◽  
Janet S. Butel ◽  
...  
Keyword(s):  
B Cells ◽  
Mammary Tumor ◽  
Mouse Mammary Tumor Virus ◽  
Envelope Gene ◽  
Mammary Tumor Virus ◽  
Mouse Mammary Tumor ◽  
Tumor Virus

Mouse mammary tumor virus gene expression regulated in trans by Lps locus

Virology ◽  
1985 ◽  
Vol 147 (1) ◽  
pp. 210-213 ◽  
Author(s):  
Jean K. Carr ◽  
Vicki L. Traina-Dorge ◽  
J.Craig Cohen
Keyword(s):  
Gene Expression ◽  
Mammary Tumor ◽  
Mouse Mammary Tumor Virus ◽  
Mammary Tumor Virus ◽  
Virus Gene ◽  
Virus Gene Expression ◽  
Mouse Mammary Tumor ◽  
Tumor Virus ◽  
In Trans

scholarly journals Preactivation of B Lymphocytes Does Not Enhance Mouse Mammary Tumor Virus Infection

1998 ◽  
Vol 72 (9) ◽  
pp. 7688-7691 ◽  
Author(s):  
Daniela Finke ◽  
Laure Mortezavi ◽  
Hans Acha-Orbea
Keyword(s):  
B Cells ◽  
B Lymphocytes ◽  
Mammary Tumor ◽  
Mouse Mammary Tumor Virus ◽  
Mammary Tumor Virus ◽  
Cell Responses ◽  
Mouse Mammary Tumor ◽  
Tumor Virus ◽  
Lower Infection

ABSTRACT We investigated whether mouse mammary tumor virus (MMTV) favors preactivated or naive B cells as targets for efficient infection. We have demonstrated previously that MMTV activates B cells upon infection. Here, we show that polyclonal activation of B cells leads instead to lower infection levels and attenuated superantigen-specific T-cell responses in vivo. This indicates that naive small resting B cells are the major targets of MMTV infection and that the activation induced by MMTV is sufficient to allow efficient infection.

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