The Experts below are selected from a list of 231 Experts worldwide ranked by ideXlab platform

Michael B. A. Oldstone - One of the best experts on this subject based on the ideXlab platform.

  • A Jekyll and Hyde Profile: Type 1 Interferon Signaling Plays a Prominent Role in the Initiation and Maintenance of a Persistent Virus Infection
    Journal of Infectious Diseases, 2015
    Co-Authors: Michael B. A. Oldstone
    Abstract:

    The hallmarks of Persistent viral Infections are exhaustion of Virus-specific T cells, elevated production of interleukin 10 (IL-10) and programmed death-1 (PD-1) the dominant negative regulators of the immune system and disruption of secondary lymphoid tissues. Within the first 12-24 hours after mice are infected with lymphocytic choriomeningitis Virus (LCMV) clone 13, which is used as a model of Persistent Virus Infection, we note generation of high titers of type 1 interferon. Blockade of type 1 interferon significantly lessens IL-10 and PD-1/PD-L1, allows normal secondary lymphoid architecture and re-establishes antiviral T-cell function, thus eradicating the Virus and clearing the Infection. Hence, type 1 interferon is a master reostat for establishing Persistent viral Infection.

  • networking at the level of host immunity immune cell interactions during Persistent viral Infections
    Cell Host & Microbe, 2013
    Co-Authors: Laura M. Snell, David G. Brooks, Michael B. A. Oldstone
    Abstract:

    Persistent viral Infections are the result of a series of connected events that culminate in diminished immunity and the inability to eliminate Infection. By building our understanding of how distinct components of the immune system function both individually and collectively in productive versus abortive responses, new potential therapeutic targets can be developed to overcome immune dysfunction and thus fight Persistent Infections. Using lymphocytic choriomeningitis Virus (LCMV) as a model of a Persistent Virus Infection and drawing parallels to Persistent human viral Infections such as human immunodeficiency Virus (HIV) and hepatitis C Virus (HCV), we describe the cellular relationships and interactions that determine the outcome of initial Infection and highlight immune targets for therapeutic intervention to prevent or treat Persistent Infections. Ultimately, these findings will further our understanding of the immunologic basis of Persistent viral Infection and likely lead to strategies to treat human viral Infections.

  • Persistent lcmv Infection is controlled by blockade of type i interferon signaling
    Science, 2013
    Co-Authors: John R Teijaro, Megan J. Welch, Andrew M Lee, Brian M Sullivan, Kathleen C F Sheehan, Robert D Schreiber, Juan Carlos De La Torre, Michael B. A. Oldstone
    Abstract:

    During Persistent viral Infections, chronic immune activation, negative immune regulator expression, an elevated interferon signature, and lymphoid tissue destruction correlate with disease progression. We demonstrated that blockade of type I interferon (IFN-I) signaling using an IFN-I receptor neutralizing antibody reduced immune system activation, decreased expression of negative immune regulatory molecules, and restored lymphoid architecture in mice Persistently infected with lymphocytic choriomeningitis Virus. IFN-I blockade before and after establishment of Persistent Virus Infection resulted in enhanced Virus clearance and was CD4 T cell–dependent. Hence, we demonstrate a direct causal link between IFN-I signaling, immune activation, negative immune regulator expression, lymphoid tissue disorganization, and Virus persistence. Our results suggest that therapies targeting IFN-I may help control Persistent Virus Infections.

  • cd8 t cell defect of tnf α and il 2 in dnam 1 deficient mice delays clearance in vivo of a Persistent Virus Infection
    Virology, 2012
    Co-Authors: Megan J. Welch, John R Teijaro, Hanna Lewicki, Marco Colonna, Michael B. A. Oldstone
    Abstract:

    DNAM-1 gene-deficient (−/−) mice take significantly longer to clear an acute and Persistent LCMV Infection in vivo than DNAM-1 +/+ mice. During acute LCMV priming, at the single cell level, DNAM-1 −/− mice made significantly less cytoplasmic CD8 TNF-α and IL-2 but not IFN-γ than their DNAM-1 +/+ counterparts. Restimulated immune memory CD8 T cells from DNAM-1 −/− and DNAM-1 +/+ mice were equivalent in cytolytic activity against LCMV-infected target cells but DNAM-1 −/− CD8 T cells had significant reductions in TNF-α and IL-2 that were associated on adoptive transfer with the inability to terminate the Persistent viral Infection.

  • Toll-like receptor 7 is required for effective adaptive immune responses that prevent Persistent Virus Infection.
    Cell host & microbe, 2012
    Co-Authors: Kevin B. Walsh, John R Teijaro, Megan J. Welch, Elina I. Zuniga, Daniel M. Fremgen, Shawn D. Blackburn, Karl F. Von Tiehl, E. John Wherry, Richard A. Flavell, Michael B. A. Oldstone
    Abstract:

    TLR7 is an innate signaling receptor that recognizes single-stranded viral RNA and is activated by Viruses that cause Persistent Infections. We show that TLR7 signaling dictates either clearance or establishment of life-long chronic Infection by lymphocytic choriomeningitis Virus (LCMV) Cl 13 but does not affect clearance of the acute LCMV Armstrong 53b strain. TLR7(-/-) mice infected with LCMV Cl 13 remained viremic throughout life from defects in the adaptive antiviral immune response-notably, diminished T cell function, exacerbated T cell exhaustion, decreased plasma cell maturation, and negligible antiviral antibody production. Adoptive transfer of TLR7(+/+) LCMV immune memory cells that enhanced clearance of Persistent LCMV Cl 13 Infection in TLR7(+/+) mice failed to purge LCMV Cl 13 Infection in TLR7(-/-) mice, demonstrating that a TLR7-deficient environment renders antiviral responses ineffective. Therefore, methods that promote TLR7 signaling are promising treatment strategies for chronic viral Infections.

David G. Brooks - One of the best experts on this subject based on the ideXlab platform.

  • Overcoming CD4 Th1 Cell Fate Restrictions to Sustain Antiviral CD8 T Cells and Control Persistent Virus Infection
    Cell reports, 2016
    Co-Authors: Laura M. Snell, Ivan Osokine, Douglas H. Yamada, Justin Rafael De La Fuente, Heidi Elsaesser, David G. Brooks
    Abstract:

    Viral persistence specifically inhibits CD4 Th1 responses and promotes Tfh immunity, but the mechanisms that suppress Th1 cells and the disease consequences of their loss are unclear. Here, we demonstrate that the loss of CD4 Th1 cells specifically leads to progressive CD8 T cell decline and dysfunction during viral persistence. Therapeutically reconstituting CD4 Th1 cells restored CD4 T cell polyfunctionality, enhanced antiviral CD8 T cell numbers and function, and enabled viral control. Mechanistically, combined interaction of PD-L1 and IL-10 by suppressive dendritic cell subsets inhibited new CD4 Th1 cells in both acute and Persistent Virus Infection, demonstrating an unrecognized suppressive function for PD-L1 in Virus Infection. Thus, the loss of CD4 Th1 cells is a key event leading to progressive CD8 T cell demise during viral persistence with important implications for restoring antiviral CD8 T cell immunity to control Persistent viral Infection.

  • type i interferon suppresses de novo Virus specific cd4 th1 immunity during an established Persistent viral Infection
    Proceedings of the National Academy of Sciences of the United States of America, 2014
    Co-Authors: Ivan Osokine, Laura M. Snell, Douglas H. Yamada, Heidi Elsaesser, Juan Carlos De La Torre, Cameron R Cunningham, Elizabeth B Wilson, David G. Brooks
    Abstract:

    CD4 T cells are central to orchestrate, sustain, and potentially regenerate antiviral immunity throughout Persistent viral Infections. Although the evolving immune environment during Persistent Infection reshapes established CD4 T-cell responses, the fate of naive CD4 T cells primed in the midst of Persistent Infection is unclear. We demonstrate that, in marked contrast to the onset of Infection, Virus-specific CD4 T cells primed during an established Persistent Infection have diminished ability to develop Th1 responses, to efficiently accumulate in peripheral tissues, and almost exclusively differentiate into T follicular helper cells. Consistent with suppressed Th1 and heightened Tfh differentiation, Virus-specific CD4 T cells primed during the established Persistent Infection provide help to B cells, but only limited help to CD8 T cells. The suppression of de novo Th1 generation and tissue distribution was mediated by chronic type I IFN (IFN-I) production and was effectively restored by blocking IFN-I signaling during CD4 T-cell priming. Thus, we establish a suppressive function of chronic IFN-I signaling and mechanism of immunoregulation during an established Persistent Virus Infection.

  • Impaired antibody effector function during Persistent viral Infection (VIR7P.1049)
    Journal of Immunology, 2014
    Co-Authors: Douglas H. Yamada, Heidi Elsaesser, David G. Brooks
    Abstract:

    Persistent viral Infections are associated with dysfunctional B cell responses including polyclonal B cell activation, non-Virus-specific hypergammaglobulinemia, and ultimately the inability to control Infection. Using the lymphocytic choriomeningitis Virus (LCMV) system of murine Infection, we addressed whether similar to other antiviral mechanisms, the suppressive immune environment generated during Persistent Infection impacted antibody effector function. We demonstrate that high levels of circulating antibodies generated during Persistent Infection (termed hypergammaglobulinemia) impede antibody dependent phagocytosis and cell killing. As a result, otherwise highly efficacious cell killing antibodies are ineffective during Persistent Virus Infection. Since antibodies are essential to the control of Persistent Infection, these observations have important implications immunologically for understanding the complex control of viral replication by antibodies as well as therapeutically for antibody immunotherapies aimed at viral clearance and secondary co-Infections. Thus, we have identified a previously unrecognized mechanism of immune dysfunction during viral persistence with important implications for understanding the mechanisms of antibody function/dysfunction and affecting their ability to kill infected cells to control Persistent Virus Infection.

  • networking at the level of host immunity immune cell interactions during Persistent viral Infections
    Cell Host & Microbe, 2013
    Co-Authors: Laura M. Snell, David G. Brooks, Michael B. A. Oldstone
    Abstract:

    Persistent viral Infections are the result of a series of connected events that culminate in diminished immunity and the inability to eliminate Infection. By building our understanding of how distinct components of the immune system function both individually and collectively in productive versus abortive responses, new potential therapeutic targets can be developed to overcome immune dysfunction and thus fight Persistent Infections. Using lymphocytic choriomeningitis Virus (LCMV) as a model of a Persistent Virus Infection and drawing parallels to Persistent human viral Infections such as human immunodeficiency Virus (HIV) and hepatitis C Virus (HCV), we describe the cellular relationships and interactions that determine the outcome of initial Infection and highlight immune targets for therapeutic intervention to prevent or treat Persistent Infections. Ultimately, these findings will further our understanding of the immunologic basis of Persistent viral Infection and likely lead to strategies to treat human viral Infections.

  • il 10 blockade facilitates dna vaccine induced t cell responses and enhances clearance of Persistent Virus Infection
    Journal of Experimental Medicine, 2008
    Co-Authors: David G. Brooks, Heidi Elsaesser, Andrew M Lee, Dorian B Mcgavern, Michael B. A. Oldstone
    Abstract:

    Therapeutic vaccination is a potentially powerful strategy to establish immune control and eradicate Persistent viral Infections. Large and multifunctional antiviral T cell responses are associated with control of viral persistence; however, for reasons that were mostly unclear, current therapeutic vaccination approaches to restore T cell immunity and control viral Infection have been ineffective. Herein, we confirmed that neutralization of the immunosuppressive factor interleukin (IL)-10 stimulated T cell responses and improved control of established Persistent lymphocytic choriomeningitis Virus (LCMV) Infection. Importantly, blockade of IL-10 also allowed an otherwise ineffective therapeutic DNA vaccine to further stimulate antiviral immunity, thereby increasing T cell responses and enhancing clearance of Persistent LCMV replication. We therefore propose that a reason that current therapeutic vaccination strategies fail to resurrect/sustain T cell responses is because they do not alleviate the immunosuppressive environment. Consequently, blocking key suppressive factors could render ineffective vaccines more efficient at improving T cell immunity, and thereby allow immune-mediated control of Persistent viral Infection.

Heidi Elsaesser - One of the best experts on this subject based on the ideXlab platform.

  • Overcoming CD4 Th1 Cell Fate Restrictions to Sustain Antiviral CD8 T Cells and Control Persistent Virus Infection
    Cell reports, 2016
    Co-Authors: Laura M. Snell, Ivan Osokine, Douglas H. Yamada, Justin Rafael De La Fuente, Heidi Elsaesser, David G. Brooks
    Abstract:

    Viral persistence specifically inhibits CD4 Th1 responses and promotes Tfh immunity, but the mechanisms that suppress Th1 cells and the disease consequences of their loss are unclear. Here, we demonstrate that the loss of CD4 Th1 cells specifically leads to progressive CD8 T cell decline and dysfunction during viral persistence. Therapeutically reconstituting CD4 Th1 cells restored CD4 T cell polyfunctionality, enhanced antiviral CD8 T cell numbers and function, and enabled viral control. Mechanistically, combined interaction of PD-L1 and IL-10 by suppressive dendritic cell subsets inhibited new CD4 Th1 cells in both acute and Persistent Virus Infection, demonstrating an unrecognized suppressive function for PD-L1 in Virus Infection. Thus, the loss of CD4 Th1 cells is a key event leading to progressive CD8 T cell demise during viral persistence with important implications for restoring antiviral CD8 T cell immunity to control Persistent viral Infection.

  • type i interferon suppresses de novo Virus specific cd4 th1 immunity during an established Persistent viral Infection
    Proceedings of the National Academy of Sciences of the United States of America, 2014
    Co-Authors: Ivan Osokine, Laura M. Snell, Douglas H. Yamada, Heidi Elsaesser, Juan Carlos De La Torre, Cameron R Cunningham, Elizabeth B Wilson, David G. Brooks
    Abstract:

    CD4 T cells are central to orchestrate, sustain, and potentially regenerate antiviral immunity throughout Persistent viral Infections. Although the evolving immune environment during Persistent Infection reshapes established CD4 T-cell responses, the fate of naive CD4 T cells primed in the midst of Persistent Infection is unclear. We demonstrate that, in marked contrast to the onset of Infection, Virus-specific CD4 T cells primed during an established Persistent Infection have diminished ability to develop Th1 responses, to efficiently accumulate in peripheral tissues, and almost exclusively differentiate into T follicular helper cells. Consistent with suppressed Th1 and heightened Tfh differentiation, Virus-specific CD4 T cells primed during the established Persistent Infection provide help to B cells, but only limited help to CD8 T cells. The suppression of de novo Th1 generation and tissue distribution was mediated by chronic type I IFN (IFN-I) production and was effectively restored by blocking IFN-I signaling during CD4 T-cell priming. Thus, we establish a suppressive function of chronic IFN-I signaling and mechanism of immunoregulation during an established Persistent Virus Infection.

  • Impaired antibody effector function during Persistent viral Infection (VIR7P.1049)
    Journal of Immunology, 2014
    Co-Authors: Douglas H. Yamada, Heidi Elsaesser, David G. Brooks
    Abstract:

    Persistent viral Infections are associated with dysfunctional B cell responses including polyclonal B cell activation, non-Virus-specific hypergammaglobulinemia, and ultimately the inability to control Infection. Using the lymphocytic choriomeningitis Virus (LCMV) system of murine Infection, we addressed whether similar to other antiviral mechanisms, the suppressive immune environment generated during Persistent Infection impacted antibody effector function. We demonstrate that high levels of circulating antibodies generated during Persistent Infection (termed hypergammaglobulinemia) impede antibody dependent phagocytosis and cell killing. As a result, otherwise highly efficacious cell killing antibodies are ineffective during Persistent Virus Infection. Since antibodies are essential to the control of Persistent Infection, these observations have important implications immunologically for understanding the complex control of viral replication by antibodies as well as therapeutically for antibody immunotherapies aimed at viral clearance and secondary co-Infections. Thus, we have identified a previously unrecognized mechanism of immune dysfunction during viral persistence with important implications for understanding the mechanisms of antibody function/dysfunction and affecting their ability to kill infected cells to control Persistent Virus Infection.

  • il 10 blockade facilitates dna vaccine induced t cell responses and enhances clearance of Persistent Virus Infection
    Journal of Experimental Medicine, 2008
    Co-Authors: David G. Brooks, Heidi Elsaesser, Andrew M Lee, Dorian B Mcgavern, Michael B. A. Oldstone
    Abstract:

    Therapeutic vaccination is a potentially powerful strategy to establish immune control and eradicate Persistent viral Infections. Large and multifunctional antiviral T cell responses are associated with control of viral persistence; however, for reasons that were mostly unclear, current therapeutic vaccination approaches to restore T cell immunity and control viral Infection have been ineffective. Herein, we confirmed that neutralization of the immunosuppressive factor interleukin (IL)-10 stimulated T cell responses and improved control of established Persistent lymphocytic choriomeningitis Virus (LCMV) Infection. Importantly, blockade of IL-10 also allowed an otherwise ineffective therapeutic DNA vaccine to further stimulate antiviral immunity, thereby increasing T cell responses and enhancing clearance of Persistent LCMV replication. We therefore propose that a reason that current therapeutic vaccination strategies fail to resurrect/sustain T cell responses is because they do not alleviate the immunosuppressive environment. Consequently, blocking key suppressive factors could render ineffective vaccines more efficient at improving T cell immunity, and thereby allow immune-mediated control of Persistent viral Infection.

Laura M. Snell - One of the best experts on this subject based on the ideXlab platform.

  • Overcoming CD4 Th1 Cell Fate Restrictions to Sustain Antiviral CD8 T Cells and Control Persistent Virus Infection
    Cell reports, 2016
    Co-Authors: Laura M. Snell, Ivan Osokine, Douglas H. Yamada, Justin Rafael De La Fuente, Heidi Elsaesser, David G. Brooks
    Abstract:

    Viral persistence specifically inhibits CD4 Th1 responses and promotes Tfh immunity, but the mechanisms that suppress Th1 cells and the disease consequences of their loss are unclear. Here, we demonstrate that the loss of CD4 Th1 cells specifically leads to progressive CD8 T cell decline and dysfunction during viral persistence. Therapeutically reconstituting CD4 Th1 cells restored CD4 T cell polyfunctionality, enhanced antiviral CD8 T cell numbers and function, and enabled viral control. Mechanistically, combined interaction of PD-L1 and IL-10 by suppressive dendritic cell subsets inhibited new CD4 Th1 cells in both acute and Persistent Virus Infection, demonstrating an unrecognized suppressive function for PD-L1 in Virus Infection. Thus, the loss of CD4 Th1 cells is a key event leading to progressive CD8 T cell demise during viral persistence with important implications for restoring antiviral CD8 T cell immunity to control Persistent viral Infection.

  • type i interferon suppresses de novo Virus specific cd4 th1 immunity during an established Persistent viral Infection
    Proceedings of the National Academy of Sciences of the United States of America, 2014
    Co-Authors: Ivan Osokine, Laura M. Snell, Douglas H. Yamada, Heidi Elsaesser, Juan Carlos De La Torre, Cameron R Cunningham, Elizabeth B Wilson, David G. Brooks
    Abstract:

    CD4 T cells are central to orchestrate, sustain, and potentially regenerate antiviral immunity throughout Persistent viral Infections. Although the evolving immune environment during Persistent Infection reshapes established CD4 T-cell responses, the fate of naive CD4 T cells primed in the midst of Persistent Infection is unclear. We demonstrate that, in marked contrast to the onset of Infection, Virus-specific CD4 T cells primed during an established Persistent Infection have diminished ability to develop Th1 responses, to efficiently accumulate in peripheral tissues, and almost exclusively differentiate into T follicular helper cells. Consistent with suppressed Th1 and heightened Tfh differentiation, Virus-specific CD4 T cells primed during the established Persistent Infection provide help to B cells, but only limited help to CD8 T cells. The suppression of de novo Th1 generation and tissue distribution was mediated by chronic type I IFN (IFN-I) production and was effectively restored by blocking IFN-I signaling during CD4 T-cell priming. Thus, we establish a suppressive function of chronic IFN-I signaling and mechanism of immunoregulation during an established Persistent Virus Infection.

  • networking at the level of host immunity immune cell interactions during Persistent viral Infections
    Cell Host & Microbe, 2013
    Co-Authors: Laura M. Snell, David G. Brooks, Michael B. A. Oldstone
    Abstract:

    Persistent viral Infections are the result of a series of connected events that culminate in diminished immunity and the inability to eliminate Infection. By building our understanding of how distinct components of the immune system function both individually and collectively in productive versus abortive responses, new potential therapeutic targets can be developed to overcome immune dysfunction and thus fight Persistent Infections. Using lymphocytic choriomeningitis Virus (LCMV) as a model of a Persistent Virus Infection and drawing parallels to Persistent human viral Infections such as human immunodeficiency Virus (HIV) and hepatitis C Virus (HCV), we describe the cellular relationships and interactions that determine the outcome of initial Infection and highlight immune targets for therapeutic intervention to prevent or treat Persistent Infections. Ultimately, these findings will further our understanding of the immunologic basis of Persistent viral Infection and likely lead to strategies to treat human viral Infections.

Douglas H. Yamada - One of the best experts on this subject based on the ideXlab platform.

  • Overcoming CD4 Th1 Cell Fate Restrictions to Sustain Antiviral CD8 T Cells and Control Persistent Virus Infection
    Cell reports, 2016
    Co-Authors: Laura M. Snell, Ivan Osokine, Douglas H. Yamada, Justin Rafael De La Fuente, Heidi Elsaesser, David G. Brooks
    Abstract:

    Viral persistence specifically inhibits CD4 Th1 responses and promotes Tfh immunity, but the mechanisms that suppress Th1 cells and the disease consequences of their loss are unclear. Here, we demonstrate that the loss of CD4 Th1 cells specifically leads to progressive CD8 T cell decline and dysfunction during viral persistence. Therapeutically reconstituting CD4 Th1 cells restored CD4 T cell polyfunctionality, enhanced antiviral CD8 T cell numbers and function, and enabled viral control. Mechanistically, combined interaction of PD-L1 and IL-10 by suppressive dendritic cell subsets inhibited new CD4 Th1 cells in both acute and Persistent Virus Infection, demonstrating an unrecognized suppressive function for PD-L1 in Virus Infection. Thus, the loss of CD4 Th1 cells is a key event leading to progressive CD8 T cell demise during viral persistence with important implications for restoring antiviral CD8 T cell immunity to control Persistent viral Infection.

  • type i interferon suppresses de novo Virus specific cd4 th1 immunity during an established Persistent viral Infection
    Proceedings of the National Academy of Sciences of the United States of America, 2014
    Co-Authors: Ivan Osokine, Laura M. Snell, Douglas H. Yamada, Heidi Elsaesser, Juan Carlos De La Torre, Cameron R Cunningham, Elizabeth B Wilson, David G. Brooks
    Abstract:

    CD4 T cells are central to orchestrate, sustain, and potentially regenerate antiviral immunity throughout Persistent viral Infections. Although the evolving immune environment during Persistent Infection reshapes established CD4 T-cell responses, the fate of naive CD4 T cells primed in the midst of Persistent Infection is unclear. We demonstrate that, in marked contrast to the onset of Infection, Virus-specific CD4 T cells primed during an established Persistent Infection have diminished ability to develop Th1 responses, to efficiently accumulate in peripheral tissues, and almost exclusively differentiate into T follicular helper cells. Consistent with suppressed Th1 and heightened Tfh differentiation, Virus-specific CD4 T cells primed during the established Persistent Infection provide help to B cells, but only limited help to CD8 T cells. The suppression of de novo Th1 generation and tissue distribution was mediated by chronic type I IFN (IFN-I) production and was effectively restored by blocking IFN-I signaling during CD4 T-cell priming. Thus, we establish a suppressive function of chronic IFN-I signaling and mechanism of immunoregulation during an established Persistent Virus Infection.

  • Impaired antibody effector function during Persistent viral Infection (VIR7P.1049)
    Journal of Immunology, 2014
    Co-Authors: Douglas H. Yamada, Heidi Elsaesser, David G. Brooks
    Abstract:

    Persistent viral Infections are associated with dysfunctional B cell responses including polyclonal B cell activation, non-Virus-specific hypergammaglobulinemia, and ultimately the inability to control Infection. Using the lymphocytic choriomeningitis Virus (LCMV) system of murine Infection, we addressed whether similar to other antiviral mechanisms, the suppressive immune environment generated during Persistent Infection impacted antibody effector function. We demonstrate that high levels of circulating antibodies generated during Persistent Infection (termed hypergammaglobulinemia) impede antibody dependent phagocytosis and cell killing. As a result, otherwise highly efficacious cell killing antibodies are ineffective during Persistent Virus Infection. Since antibodies are essential to the control of Persistent Infection, these observations have important implications immunologically for understanding the complex control of viral replication by antibodies as well as therapeutically for antibody immunotherapies aimed at viral clearance and secondary co-Infections. Thus, we have identified a previously unrecognized mechanism of immune dysfunction during viral persistence with important implications for understanding the mechanisms of antibody function/dysfunction and affecting their ability to kill infected cells to control Persistent Virus Infection.