Molecular Localization of Envelope Gene Sequence of Human Mammary Tumor Virus in Malignant Endometrial and Cervical Tissues from Iraqi Patients in Baghdad

ABSTRACT Mouse mammary tumor virus (MMTV) has been classified as a simple retrovirus with two accessory genes, dut and sag. Cloned MMTV proviruses carrying a trimethoprim (trim) cassette in the envelope gene were defective for Gag protein production and the nuclear export of unspliced gag-pol RNA. Complementation experiments indicated that a trans-acting product was responsible for the Gag defect of such mutants. Analysis of MMTV-infected cells revealed the presence of a novel, doubly spliced RNA that encodes a putative product of 301 amino acids. Overexpression of cDNA from this RNA increased Gag levels from env mutant proviruses or reporter gene expression from unspliced mRNAs and allowed detection of a 33-kDa protein product, which has been named regulator of export of MMTV mRNA, or Rem. The Rem N terminus has motifs similar to the Rev-like export proteins of complex retroviruses, and mutation of the nuclear localization signal (NLS) abolished RNA export and detection within the nucleus. The Rem C terminus has few identifiable features, but removal of this domain increased Rem-mediated export, suggesting an autoregulatory function. A reporter vector developed from the 3′ end of the MMTV provirus was Rem responsive and required both the presence of the MMTV env-U3 junction and a functional Crm1 pathway. The identification of a third accessory protein from a doubly spliced transcript suggests that MMTV is the first murine complex retrovirus to be documented. Manipulation of the MMTV genome may provide mouse models for human retroviral diseases, such as AIDS.

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The mouse mammary tumor virus envelope gene product is required for superantigen presentation to T cells.

Journal of Experimental Medicine ◽

10.1084/jem.179.2.439 ◽

1994 ◽

Vol 179 (2) ◽

pp. 439-446 ◽

Cited By ~ 33

Author(s):

T V Golovkina ◽

A Chervonsky ◽

J A Prescott ◽

C A Janeway ◽

S R Ross

Keyword(s):

T Cells ◽

T Cell ◽

Gene Product ◽

Mammary Tumor ◽

Mouse Mammary Tumor Virus ◽

Envelope Gene ◽

Mammary Tumor Virus ◽

Cell Surface Glycoprotein ◽

Mouse Mammary Tumor ◽

Tumor Virus

Transgenic mice expressing either the mouse mammary tumor virus (MMTV) superantigen gene (sag) alone or in combination with the viral envelope genes (env) (LEL), or all of the viral genes (gag, pol, env, and sag) (HYB PRO), deleted V beta 14+ T cells from their immune repertoire. However, only LEL or HYB PRO transgenic antigen-presenting cells were capable of stimulating a proliferative response from nontransgenic primary T cells or interleukin 2 production from a V beta 15-bearing T cell hybridoma. These T cell responses could be inhibited by a monospecific antibody directed against the MMTV gp52 cell surface glycoprotein. These results indicate that the MMTV gp52 gene product participates in the presentation of superantigen to T cells, resulting in their stimulation, a requisite step in the MMTV infection pathway. Thus, gp52 could play a role in the transfer of virus between different subsets of lymphocytes.

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