Progression of a vesicular stomatitis virus infection in primary lymphocytes is restricted at multiple levels during B cell activation.
Small resting B cells do not support a productive vesicular stomatitis virus (VSV) infection, but are induced by B cell activators to become fully permissive for VSV replication. Nonpermissive B cell populations restrict VSV expression at multiple points: transcript levels, translation, and maturation. Unstimulated resting G0 B cells can be infected by VSV and support the synthesis of all VSV mRNAs. Steady-state levels of viral transcripts are selectively enhanced by T cell-derived cytokines to an extent comparable with that seen for cytokine-regulated cellular mRNAs. However, viral proteins are not detected in immunoprecipitates from unstimulated or cytokine-stimulated B cells despite the fact that viral mRNAs are associated with polysomes and can be translated in vitro. This translational block is released by stimulation of infected B cells with mitogenic anti-lg or LPS, or non-mitogenic PMA. VSV virion maturation is also regulated by activation signals, because neither anti-lg nor PMA-stimulated B cells produce high levels of infectious VSV particles. Because anti-lg stimulation supports viral genome replication, maturational arrest is apparently at virus assembly or release. PMA and ionomycin induces changes beyond those seen with anti-lg, because these B cells produce PFUs at levels comparable with those seen with LPS-activated B cells and VSV-permissive cell lines. Activation-dependent regulation of virus expression provides a new paradigm for assessing activator-induced events in B cell differentiation not revealed by previous assessments of proliferation of Ab synthesis.
Schmidt
M R
MR
Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, Worcester 01655, USA.
Gravel
K A
KA
Woodland
R T
RT
D000818:Animals; D001402:B-Lymphocytes / Q000821:virology*; D005260:Female; D007136:Immunoglobulins / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D008808:Mice, Inbred CBA; D010835:Phytohemagglutinins / Q000494:pharmacology; D014176:Protein Biosynthesis / Q000187:drug effects / Q000276:immunology; D012367:RNA, Viral / Q000032:analysis; D018353:Rhabdoviridae Infections / Q000276:immunology / Q000517:prevention & control / Q000628:therapy*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D014721:Vesicular stomatitis Indiana virus / Q000235:genetics; D010948:Viral Plaque Assay; D014764:Viral Proteins / Q000032:analysis; D014779:Virus Replication / Q000187:drug effects / Q000276:immunology*
D007136:Immunoglobulins; D008070:Lipopolysaccharides; D010835:Phytohemagglutinins; D012367:RNA, Viral; D014764:Viral Proteins