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      The role of gamma interferon in infection of susceptible mice with murine coronavirus, MHV-JHM


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          Infection of BALB/c mice with mouse hepatitis virus, strain JHM (MHV-JHM), at any of several intervals relative to ovalbumin (OVA) administration resulted in elevated OVA-specific IgG 2 a titers. Since gamma interferon (IFN) has been implicated as an up-regulator of IgG 2 a production, attempts were made to determine whether levels of this cytokine were modified in sera of infected mice. Serum IFN-γ was not detected, but treatment of MHV-JHM-infected mice with monoclonal anti-IFN-γ antibody resulted in high mortality with decreased survival times, enhanced virus titers in liver and spleen, and more severe virus-associated pathology, compared to mock-treated, infected mice. Immunotherapy with recombinant IFN-γ ameliorated disease as reflected by mortality rates and virus titers in target organs.

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          Most cited references32

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          Interferon-gamma and B cell stimulatory factor-1 reciprocally regulate Ig isotype production.

          Gamma interferon (IFN-gamma) and B cell stimulatory factor-1 (BSF-1), also known as interleukin-4, are T cell-derived lymphokines that have potent effects on B cell proliferation and differentiation. They are often secreted by distinct T cell clones. It is now shown that IFN-gamma stimulates the expression of immunoglobulin (Ig) of the IgG2a isotype and inhibits the production of IgG3, IgG1, IgG2b, and IgE. By contrast, BSF-1 has powerful effects in promoting switching to the expression of IgG1 and IgE but markedly inhibits IgM, IgG3, IgG2a, and IgG2b. These results indicate that BSF-1 and IFN-gamma as well as the T cells that produce them may act as reciprocal regulatory agents in the determination of Ig isotype responses. The effects of IFN-gamma and BSF-1 on isotype expression are independent.
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            IFN-gamma regulates the isotypes of Ig secreted during in vivo humoral immune responses.

            The lymphokine IFN-gamma has been shown in vitro to stimulate IgG2a secretion and inhibit IgG1 and IgE secretion by LPS-activated B lymphocytes. To determine whether IFN-gamma has a similar isotype regulatory role in vivo, we studied the abilities of rIFN-gamma and a mAb to IFN-gamma to modify the isotypes of Ig secreted in mice injected with a goat antibody to mouse IgD, which by itself induces large increases in levels of serum IgG1 and IgE and a relatively small increase in serum IgG2a. Multiple injections of IFN-gamma substantially inhibited production of IgG1 and IgE, and stimulated production of IgG2a in affinity purified goat antibody specific for mouse IgD-treated mice; anti-IFN-gamma antibody blocked the effects of IFN-gamma and in fact enhanced IgG1 and IgE secretion and inhibited the IgG2a response in these mice. The role of IFN-gamma in the selection of isotypes of Ig produced in response to injection of mice with the bacterium Brucella abortus (BA) was also studied, because killed, fixed BA are known to stimulate IFN secretion and a predominantly IgG2a antibody response. Anti-IFN-gamma antibody strongly suppressed IgG2a secretion and stimulated IgG1, but not IgE, secretion in BA-immunized mice. BA suppressed IgG1 and IgE secretion and enhanced IgG2a secretion in affinity purified goat antibody specific for mouse IgD-injected mice; treatment of these mice with anti-IFN-gamma antibody reversed the effects of BA on IgG1 and IgG2a secretion, but not the suppressive effect of BA on IgE secretion. These observations demonstrate that IFN-gamma has an important and perhaps unique physiologic role in the stimulation of IgG2a secretion and in the suppression of secretion of IgG1, whereas bacterial antigens can suppress IgE secretion by other mechanisms in addition to IFN-gamma secretion.
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              An immunofluorescence test for detection of serum antibody to rodent coronaviruses.

              A Smith (1983)
              An indirect immunofluorescence test, using cultured cells infected with two strains of mouse hepatitis virus, was developed for detection of antibody to rodent coronaviruses. The immunofluorescence test detected serum antibody to mouse hepatitis virus and rat sialodacryoadenitis virus earlier than the neutralization test. In the case of mouse hepatitis virus, the results of the immunofluorescence test closely paralleled those obtained with a commercially available enzyme-linked immunosorbent assay.

                Author and article information

                Arch Virol
                Arch. Virol
                Archives of Virology
                Springer-Verlag (Vienna )
                : 121
                : 1
                : 89-100
                [1 ]GRID grid.47100.32, ISNI 0000000419368710, Section of Comparative Medicine, , Yale University School of Medicine, ; New Haven, Connecticut U.S.A.
                [2 ]GRID grid.47100.32, ISNI 0000000419368710, Department of Epidemiology and Public Health, , Yale University School of Medicine, ; New Haven, Connecticut U.S.A.
                [3 ]GRID grid.47100.32, ISNI 0000000419368710, Howard Hughes Medical Institute and Section of Immunobiology, , Yale University School of Medicine, ; New Haven, Connecticut U.S.A.
                © Springer-Verlag 1991

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                : 26 January 1991
                : 31 March 1991
                Original Papers
                Custom metadata
                © Springer-Verlag 1991

                Microbiology & Virology
                hepatitis,mortality rate,infectious disease,interferon,survival time
                Microbiology & Virology
                hepatitis, mortality rate, infectious disease, interferon, survival time


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