Initial Stages of Mammary Tumor Virus Infection Are Superantigen Independent

Exogenous mouse mammary tumor virus (MMTV) is transmitted via the milk from infected mothers to newborn pups. Efficient MMTV transmission is dependent on proliferation of T cells with particular TCR beta-chains, which occurs upon recognition of virally encoded superantigen (SAg) bound to MHC class II molecules. It is assumed that infection of these dividing cells favors MMTV amplification. SAg is important for MMTV infection, as mice that lack SAg-cognate T cells due to expression of endogenous Mtv loci or mice that express inappropriate MHC haplotypes unable to present viral SAg efficiently were shown to be resistant to MMTV infection. However, this resistance was not absolute, as these mice developed late onset MMTV-induced mammary tumors. In this study, we show that the success of initial MMTV infection in neonates is independent of SAg function but depends on the developmentally regulated proliferation of target cells. However, SAg was absolutely required for virus spread following completion of this proliferative stage.