REVERSE TRANSCRIPTASE-DEPENDENT AND TRANSCRIPTASE-INDEPENDENT PHASES OF INFECTION WITH MOUSE MAMMARY-TUMOR VIRUS - IMPLICATIONS FOR SUPERANTIGEN FUNCTION

Mouse mammary tumor virus (MMTV) encodes a superantigen (SAg) that pro motes stable infection and virus transmission. Upon subcutaneous MMTV injection, infected B cells present SAg to SAg-reactive T cells leadin g to a strong local immune response in the draining lymph node (LN) th at peaks after 6 d. We have used the reverse transcriptase inhibitor 3 '-azido-3'-deoxythymidine (AZT) to dissect in more detail the mechanis m of SAg-dependent enhancement of MMTV infection in this system. Our d ata show that no detectable B or T cell response to SAg occurs in AZT pretreated mice. However, if AZT treatment is delayed 1-2 d after MMTV injection, a normal SAg-dependent local immune response is observed o n day 6. Quantitation of viral DNA in draining LN of these infected mi ce indicates that a 4,000-fold increase in the absolute numbers of inf ected cells occurs between days 2 and 6 despite the presence of AZT. F urthermore MMTV DNA was found preferentially in surface IgG(+) B cells of infected mice and was not detectable in SAg-reactive T cells. Coll ectively our data suggest that MMTV infection occurs preferentially in B cells without SAg involvement and is completed 1-2 d after virus ch allenge. Subsequent amplification of MMTV infection between days 2 and 6 requires SAg expression and occurs in the absence of any further re quirement for reverse transcription. We therefore conclude that clonal expansion of infected B cells via cognate interaction with SAg-reacti ve T cells is the predominant mechanism for increasing the level of MM TV infection. Since infected B cells display a memory (surface IgG(+)) phenotype, both clonal expansion and possibly longevity of the virus carrier cells may contribute to stable MMTV infection.