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The results of this study demonstrate that murine cytomegalovirus (MCMV) induces polyclonal B cell activation in mice during the acute phase of primary infection. First flow cytometric analysis revealed that surface expression of CD45R, IgM, and IgK by splenocytes from MCMV-infected mice was significantly reduced with a concomitant increase in the frequency of surface IgG-expressing cells. Second, ELIspot assays demonstrated that the changes revealed by flow cytometry were paralleled by increases in the numbers of IgG-producing cells, especially those secreting IgG2a. Third, the IgG antibodies from MCMV-infected animals reacted against a variety of self and foreign antigens. MCMV-induced B cell activation was independent of CD4+ T-cell-mediated help and CD40, since activation was observed in two models of mice deficient for this T cell subset and in mice deficient for CD40. Reverse transcription-polymerase chain reaction analysis showed that mRNA transcripts for the cytokines IL-6, IL-10, and IFN-gamma were rapidly induced following infection with MCMV, but only IL-6 and IFN-gamma proteins were detectable by ELISA. In addition, the numbers of cells producing IL-6 and IFN-gamma were significantly increased in the spleen. The magnitude of the polyclonal B cell activation response was diminished by 50% in IL-6-deficient mice but not in mice lacking IFN-gamma. In the absence of IFN-gamma, surface expression and serum levels of IgG2a were reduced while IgG1 expression was increased.

California wild mouse-derived ecotropic virus Cas-Br-M induces a spongiform encephalopathy and a wide variety of hematopoietic neoplasms on inoculation of neonatal mice. We isolated a MCF virus [Ns-6(186) MCF] from a thymic T-cell lymphoma developing in a NFS mouse inoculated with Cas-Br-M virus. Biologically cloned NS-6(186) MCF virus, in contrast to previously studied MCF viruses, was found to induce thymic or nonthymic T-cell lymphomas with high efficiency in the absence of ecotropic helper virus. Comparison of the restriction endonuclease maps derived from Cas-Br-M and NS-6(186) MCF revealed differences only in the env region, between 5.8 and 7.8 kb from the 5' end. Two biologically active molecular clones of the NS-6(186) MCF (clone 15 with two LTRs and clone 19 with 1 LTR) were studied. Although both clones exhibited similar in vitro activities, clone 15-derived virus induced only T-cell lymphomas with short latency whereas clone 19-derived virus induced a wide variety of neoplasms with a significantly longer latency. Nucleotide sequence analysis established that the U3 region of each of the two LTRs of clone 15 has a 53-bp duplication which includes "enhancer elements," but that the single LTR of clone 19 has no such duplication.

The species host range of the recombinant, mink cell focus-inducing (MCF) class of murine retroviruses was determined in vitro and compared to the host range properties of xenotropic and amphotropic murine viruses. In contrast to xenotropic and amphotropic viruses, MCF viruses were restricted in the number of mammalian species they would infect. Cell lines from mouse, rat, mink, ferret, and cat were susceptible to MCF infection and certain virus isolates could infect rabbit cells, but cells from Chinese hamster, buffalo, bat, dog, monkey, and human were resistant to infection by most MCF viruses. The resistance of some of the latter cells was abrogated by phenotypic mixing with xenotropic virus, which demonstrated that MCF species host range was mediated by virus envelope-cell surface interaction. The host range uniformity of the various MCF isolates and the unique species distribution of sensitivity are consistent with the conclusion from other evidence that the MCF viruses comprise a class distinct from xenotropic and amphotropic viruses.