[Coevolutive mechanisms between retroviruses and their hosts. The murine mammary tumor model].
Mouse mammary tumor virus (MMTV) is a type B retrovirus that is transmitted as an infectious milk-borne particle and that causes mammary carcinomas by insertional activation of cellular protooncogenes. Germ line infections result in endogenous Mtv proviruses integrated in the genome of most mouse strains. These endogenous proviruses have been integrated into the genomes of mice for only the past 3-5 million years. The open reading frame present in the 3' long terminal repeat (LTR) of the provirus encodes a superantigen (SAg) which is able to stimulate a large proportion of T cells sharing a common T-cell receptor beta chain variable domain (v beta). Expression of this SAg is critical to the MMTV life cycle. After expression of the SAg in B cells a significant number of T cells are recruited to respond to these MMTV infected cells. As a consequence both the T cells expressing the relevant TCR V beta domain and the infected B cells become activated and start dividing. This would facilitate integration of MMTV and amplify the number of virus infected lymphocytes. Most likely during lactation the mammary glands become receptive to viral infection. The presence of endogenous Mtvs induces an early clonal deletion of reactive T cells. For this reason it has been argued that the presence of these proviruses confers a selective advantage to the mouse population by protecting the host from infection with an exogenous MMTV coding for a cross-reactive SAg. However, recent results discussed herein suggest that Mtv proviruses may also be detrimental to the mouse population by participating in recombinations with exogenous MMTVs, giving rise to highly tumorigenic recombinant particles. These results are discussed in the light of recent reports suggesting the involvement of viral sequences with a high homology to MMTV in human mammary tumorigenesis.
Nepomnaschy
I
I
División Medicina Experimental, Academia Nacional de Medicina, Buenos Aires.
Buggiano
V
V
Goldman
A
A
Piazzon
I
I
D000818:Animals; D005075:Biological Evolution; D066298:In Vitro Techniques; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics* / Q000276:immunology*; D051379:Mice; D012190:Retroviridae / Q000235:genetics* / Q000276:immunology*
Mecanismos coevolutivos entre los retrovirus y sus huéspedes. El modelo del tumor mamario murino.