Open AccessIsolation of host-range variants of mouse mammary tumor viruses that efficiently infect cells in vitro
Author(s) -
David K. Howard,
Jeffrey Schlom
Publication year - 1978
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.75.11.5718
Subject(s) - mouse mammary tumor virus , biology , virology , mammary tumor , virus , in vitro , retrovirus , cell culture , microbiology and biotechnology , genetics , cancer , breast cancer
Host-range variants of mouse mammary tumor virus (MMTV) have been isolated that have the ability to productively infect cellsin vitro with high efficiency (at multiplicities of infection ≤1) and with extremely short latent periods to the production ofde novo virus (as short as 4 days after infection). These variants of the highly oncogenic MMTV of RIII, C3H, and GR mice were obtained by serial virus passage in feline cells. The resultant variant stocks react in group-specific radioimmunoassays for the MMTV major external glycoprotein (gp52) and major internal protein (p28), possess a protein profile similar to that of wild-type MMTV, and contain a virion-associated DNA polymerase with a magnesium cation preference. Addition of dexamethasone and insulin to culture media enhances the titer ofde novo MMTV to levels of approximately 1010 particles per 75-cm2 flask (containing 5 × 106 cells) per 24 hr. Variant stocks exhibit no evidence of contamination with either murine or feline type C retroviruses, as assayed by various techniques. The variants of MMTV derived from C3H and RIII mice exhibit differential host ranges that include the ability to productively infect feline, canine, bat, mink, murine, and human cells. Use of these MMTV host-range variants now facilitates the study of the complete replicative cycle of MMTV as well as an elucidation of the interaction of MMTV with various hormones, physical or chemical carcinogens, and tumor promoters in the initiation and promotion of mammary neoplasia.