Rapid spread of mouse mammary tumor virus in cultured human breast cells.
BACKGROUND
The role of mouse mammary tumor virus (MMTV) as a causative agent in human breast carcinogenesis has recently been the subject of renewed interest. The proposed model is based on the detection of MMTV sequences in human breast cancer but not in healthy breast tissue. One of the main drawbacks to this model, however, was that until now human cells had not been demonstrated to sustain productive MMTV infection.


RESULTS
Here, we show for the first time the rapid spread of mouse mammary tumor virus, MMTV(GR), in cultured human mammary cells (Hs578T), ultimately leading to the infection of every cell in culture. The replication of the virus was monitored by quantitative PCR, quantitative RT-PCR and immunofluorescence imaging. The infected human cells expressed, upon cultivation with dexamethasone, MMTV structural proteins and released spiked B-type virions, the infectivity of which could be neutralized by anti-MMTV antibody. Replication of the virus was efficiently blocked by an inhibitor of reverse transcription, 3'-azido-3'-deoxythymidine. The human origin of the infected cells was confirmed by determining a number of integration sites hosting the provirus, which were unequivocally identified as human sequences.


CONCLUSIONS
Taken together, our results show that human cells can support replication of mouse mammary tumor virus.
Indik
Stanislav
S
Research Institute for Virology and Biomedicine, University of Veterinary Medicine Vienna, Vienna, A-1210, Austria. stanislav.indik@vu-wien.ac.at
Günzburg
Walter H
WH
Kulich
Pavel
P
Salmons
Brian
B
Rouault
Francoise
F
D000818:Animals; D001943:Breast Neoplasms / Q000821:virology*; D002460:Cell Line; D004279:DNA, Viral / Q000032:analysis / Q000235:genetics; D006801:Humans; D008324:Mammary Tumor Virus, Mouse / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D016133:Polymerase Chain Reaction / Q000379:methods; D014412:Tumor Virus Infections / Q000276:immunology; D014779:Virus Replication / Q000187:drug effects; D015215:Zidovudine / Q000494:pharmacology
D004279:DNA, Viral; D015215:Zidovudine