Host Genetic Control of Recovery From Friend Leukemia Virus-Induced Splenomegaly

Chesebro, Bruce; Wehrly, Kathy; Stimpfling, Jack H.

doi:10.1084/jem.140.6.1457

Cited by 166 publications

(101 citation statements)

References 27 publications

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“…The B-cell-tropic, polycythemia-inducing FV complex (35) was used for all virus challenge experiments and was from an uncloned virus stock obtained from a 10% spleen cell homogenate as previously described (8). Mice were inoculated by intravenous injection with 3,000 spleen focusforming units of FV complex diluted in 0.5 ml of phosphate-buffered balanced salt solution (PBBS) containing 2% fetal bovine serum.…”

Section: Methodsmentioning

confidence: 99%

Temporal Effects of Gamma Interferon Deficiency on the Course of Friend Retrovirus Infection in Mice

Stromnes

Dittmer

Schumacher

et al. 2002

J Virol

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The current studies demonstrate complex and seemingly contradictory effects by gamma interferon (IFN-␥) on Friend virus (FV) infection. Both temporal and tissue-specific effects were observed. During the first week of infection, IFN-␥-deficiency caused increased levels of FV infection in multiple tissues. Surprisingly, however, by 2 weeks postinfection, IFN-␥-deficient mice had significantly lower levels of infection in both the spleen and bone marrow compared to wild-type mice. The rapid reduction of virus in the IFN-␥-deficient mice correlated with a more rapid virus-neutralizing antibody response than was observed in the wild-type mice. Furthermore, the virus-neutralizing antibody response in wild-type mice could be accelerated by ablation of their IFN-␥ response. Although the IFN-␥-deficient mice developed an accelerated virus-neutralizing antibody response, they did not class-switch to immunoglobulin G class immunoglobulins nor could they maintain long-term virus-neutralizing antibody titers. Eventually, all of the IFN-␥-deficient mice failed to keep persistent virus in check and developed fatal FV-induced erythroleukemia.

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Section: Methodsmentioning

confidence: 99%

Temporal Effects of Gamma Interferon Deficiency on the Course of Friend Retrovirus Infection in Mice

Stromnes

Dittmer

Schumacher

et al. 2002

J Virol

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“…FV is known to induce fatal erythroleukemia associated with severe immunosuppression when injected into immunocompetent adult mice of susceptible strains (2,27). Mice with a BALB/c background are especially susceptible to FV-induced disease because they lack immune and nonimmune mechanisms that render some other strains of mice resistant against FV replication and disease progression (5). Epitopes recognized by CD4 ϩ helper T cells and CD8 ϩ cytotoxic T lymphocytes (CTL) have been identified in the products of env and gag genes of F-MuLV (1,15,20,32,36), and a yet-unidentified immunoprotective CD4 ϩ T-cell epitope has been mapped in the MA (p15) portion of the gag gene product (23).…”

mentioning

confidence: 99%

Role of Natural Killer Cells in Resistance against Friend Retrovirus-Induced Leukemia

Iwanami

Niwa

Yasutomi

et al. 2001

J Virol

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“…focus-forming units (SFFU) of virus as described previously (9). For virus challenge experiments, mice were infected by intravenous injection of 0.5 ml of phosphate-buffered balanced salt solution containing 1% normal mouse serum and 3,000 SFFU of FV.…”

mentioning

confidence: 99%

CD4⁺T Cells and Gamma Interferon in the Long-Term Control of Persistent Friend Retrovirus Infection

Iwashiro

Peterson

Messer

et al. 2001

J Virol

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We have used the Friend virus model to determine the basic mechanisms by which the immune system can control persistent retroviral infections. Previously we showed that CD4 ؉ T cells play an essential role in keeping persistent retrovirus in check. The present in vitro experiments with a Friend virus-specific CD4 ؉ T-cell clone revealed that these cells produce gamma interferon (IFN-␥), which acts with two distinct mechanisms of antiviral activity. First, IFN-␥ had a direct inhibitory effect on virus production. This inhibitory effect was noncytolytic and, interestingly, was not associated with decreased cell surface expression of viral antigens. The second mechanism of IFN-␥-mediated antiviral activity was an enhancement of CD4 ؉ T-cell-mediated cytolytic activity. We also found an in vivo role for IFN-␥ in the control of persistent Friend virus infections. Neutralization of IFN-␥ in persistently infected mice resulted in significantly increased levels of virus in the spleen, and a significant percentage of IFN-␥-deficient mice were unable to maintain long-term control over Friend virus infections.The most serious problems caused by many retroviruses often result from the effects of persistent infection rather than the initial acute phases of infection. For example, the acute phase of infection with human immunodeficiency virus (HIV) is generally resolved relatively quickly, but the virus persists and after several years results in diminished CD4ϩ T-cell levels, loss of immune functions, and the onset of AIDS. As a model for studying persistent retrovirus infections, we have used Friend virus complex (FV) in strains of mice which generally recover from acute disease but develop lifelong, lowlevel persistent infections (6, 28). Many types of cells including erythroid precursors, monocytes, and lymphocytes are initially infected with FV during the acute phase of disease (28). Recovery from the acute phase is dependent on genes of the major histocompatibility complex (MHC) and complex immune responses including cytotoxic T-lymphocyte (CTL), CD4 ϩ T-helper, and antibody responses (reviewed in references 30 and 31). Following recovery from FV-induced splenomegaly and viremia, the infection in the spleen is reduced by over 1,000-fold and appears to be primarily restricted to a very small population of B cells (28).Most persistently infected mice live a normal life span, although for unknown reasons, approximately 5% of the mice eventually relapse with FV-induced erythroleukemia (6). Unlike HIV, FV infection does not deplete CD4 ϩ T-cell levels, but if mice with persistent FV are experimentally depleted of their CD4ϩ T cells, a large percentage of the mice relapse with acute disease and develop erythroleukemia (28). Thus, CD4 ϩ T cells play a critical role in containing persistent FV infections. In contrast, depletion of CD8 ϩ T cells does not induce relapse or increased levels of persistent virus, nor is there an additive effect from dual depletion of both CD4 ϩ and CD8 ϩ T cells (28). Furthermore, CD4 depletions do ...

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Host Genetic Control of Recovery From Friend Leukemia Virus-Induced Splenomegaly

Cited by 166 publications

References 27 publications

Temporal Effects of Gamma Interferon Deficiency on the Course of Friend Retrovirus Infection in Mice

Temporal Effects of Gamma Interferon Deficiency on the Course of Friend Retrovirus Infection in Mice

Role of Natural Killer Cells in Resistance against Friend Retrovirus-Induced Leukemia

CD4⁺T Cells and Gamma Interferon in the Long-Term Control of Persistent Friend Retrovirus Infection

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Host Genetic Control of Recovery From Friend Leukemia Virus-Induced Splenomegaly

Cited by 166 publications

References 27 publications

Temporal Effects of Gamma Interferon Deficiency on the Course of Friend Retrovirus Infection in Mice

Temporal Effects of Gamma Interferon Deficiency on the Course of Friend Retrovirus Infection in Mice

Role of Natural Killer Cells in Resistance against Friend Retrovirus-Induced Leukemia

CD4+T Cells and Gamma Interferon in the Long-Term Control of Persistent Friend Retrovirus Infection

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CD4⁺T Cells and Gamma Interferon in the Long-Term Control of Persistent Friend Retrovirus Infection