Article: article from journal or magazin.
Reverse transcriptase-dependent and -independent phases of infection with mouse mammary tumor virus: implications for superantigen function.
Journal of Experimental Medicine
Mouse mammary tumor virus (MMTV) encodes a superantigen (SAg) that promotes stable infection and virus transmission. Upon subcutaneous MMTV injection, infected B cells present SAg to SAg-reactive T cells leading to a strong local immune response in the draining lymph node (LN) that peaks after 6 d. We have used the reverse transcriptase inhibitor 3'-azido-3'-deoxythymidine (AZT) to dissect in more detail the mechanism of SAg-dependent enhancement of MMTV infection in this system. Our data 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 on day 6. Quantitation of viral DNA in draining LN of these infected mice indicates that a 4,000-fold increase in the absolute numbers of infected cells occurs between days 2 and 6 despite the presence of AZT. Furthermore MMTV DNA was found preferentially in surface IgG+ B cells of infected mice and was not detectable in SAg-reactive T cells. Collectively our data suggest that MMTV infection occurs preferentially in B cells without SAg involvement and is completed 1-2 d after virus challenge. Subsequent amplification of MMTV infection between days 2 and 6 requires SAg expression and occurs in the absence of any further requirement for reverse transcription. We therefore conclude that clonal expansion of infected B cells via cognate interaction with SAg-reactive T cells is the predominant mechanism for increasing the level of MMTV 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.
Animals, B-Lymphocytes/drug effects, B-Lymphocytes/immunology, CD4-Positive T-Lymphocytes/immunology, CD4-Positive T-Lymphocytes/virology, DNA, Viral/analysis, DNA, Viral/biosynthesis, Kinetics, Lymph Nodes/immunology, Lymph Nodes/virology, Mammary Tumor Virus, Mouse/drug effects, Mammary Tumor Virus, Mouse/pathogenicity, Mice, Mice, Inbred BALB C, Mice, Inbred Strains, Phenotype, Polymerase Chain Reaction, RNA-Directed DNA Polymerase/metabolism, Superantigens/biosynthesis, T-Lymphocytes/drug effects, T-Lymphocytes/immunology, Virus Replication/drug effects, Zidovudine/pharmacology
Web of science
Last modification date