Clearance of an immunosuppressive virus from the CNS coincides with immune reanimation and diversification

Lauterbach, Henning; Truong, Phi; McGavern, Dorian B.

doi:10.1186/1743-422x-4-53

Cited by 16 publications

(25 citation statements)

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“…In contrast to Armstrong, which is cleared acutely in 8-10 days, clone 13 distributes systemically and is not purged from most peripheral tissues (e.g. serum, spleen, lymph nodes, lung, and liver) until 40-80 days post-infection (156,157). The time period preceding viral clearance is associated with profound immune exhaustion, during which LCMV-specific T cells show a diminished capacity to produce anti-viral cytokines and engage in cytolytic activities (157).…”

Section: Lcmv Clone 13 Infection and Clearance From The Cnsmentioning

confidence: 98%

“…After inoculation of adult mice with LCMV clone 13, virus is distributed throughout the body in areas including the serum, blood, spleen, liver, kidney and brain (28,153,154,156,157). In contrast to LCMV Armstrong infection, which is cleared within 2 weeks, LCMV clone 13 challenge results in persistent infection and diminished CTL responses (29, 152, compartment (166, 167).…”

Section: Lcmv Clone 13 and Chronic Infectionmentioning

confidence: 99%

“…The time period preceding viral clearance is associated with profound immune exhaustion, during which LCMV-specific T cells show a diminished capacity to produce anti-viral cytokines and engage in cytolytic activities (157). Within the CNS clearance of LCMV clone 13 is delayed considerably and does not occur until day 200 post infection (156).…”

Section: Lcmv Clone 13 Infection and Clearance From The Cnsmentioning

confidence: 99%

“…To gain novel insights into clone 13 infection of the CNS, our group recently studied clone 13 tropism and the responding CNS immune response to this variant following intravenous inoculation (156). At early time points post-infection, viral antigen was detected in the choroid plexus, meninges, ependymal cells and in regions surrounding the blood vasculature of the brain (Figure 3).…”

Section: Lcmv Clone 13 Infection and Clearance From The Cnsmentioning

confidence: 99%

“…However, in the brain conversion from LCMV Armstrong to clone 13 occurred at lower levels (151), and in general, LCMV Armstrong was observed to out compete clone 13 for infection of neurons in vitro and brain tissue upon co-infection in vivo (154, 155). These data suggested that LCMV clone 13 was a more viscerotropic variant, whereas Armstrong was a more neurotropic variant.After inoculation of adult mice with LCMV clone 13, virus is distributed throughout the body in areas including the serum, blood, spleen, liver, kidney and brain (28,153,154,156,157). In contrast to LCMV Armstrong infection, which is cleared within 2 weeks, LCMV clone 13 challenge results in persistent infection and diminished CTL responses (29, 152, compartment (166, 167).…”

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Lymphocytic choriomeningitis infection of the central nervous system

Kang

McGavern

2008

Front Biosci

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Viral infection of the central nervous system (CNS) can result in a multitude of responses including pathology, persistence or immune clearance. Lymphocytic choriomeningitis virus (LCMV) is a powerful model system to explore these potential outcomes of CNS infection due to the diversity of responses that can be achieved after viral inoculation. Several factors including tropism, timing, dose and variant of LCMV in combination with the development or suppression of the corresponding immune response dictates whether lethal meningitis, chronic infection or clearance of LCMV in the CNS will occur. Importantly, the functionality and positioning of the LCMV-specific CD8 + T cell response are critical in directing the subsequent outcome of CNS LCMV infection. Although a basic understanding of LCMV and immune interactions in the brain exists, the molecular machinery that shapes the balance between pathogenesis and clearance in the LCMV-infected CNS remains to be elucidated. This review covers the various outcomes of LCMV infection in the CNS and what is currently known about the impact of the virus itself versus the immune response in the development of disease or clearance. KeywordsLCMV; Clone 13; Virus; Meningitis; Immunotherapy; Brain; Neurons; Astrocytes; Immunodeficient; Neonates; Growth Hormone; T cell; behavior; Review INTRODUCTIONThe parameters that dictate pathology versus clearance after CNS viral infection are relatively undefined. The CNS contains highly integrated populations of neurons and glial cells responsible for our livelihood, and immune infiltration has the potential to severely disrupt the function of this sensitive compartment. Consequently, through evolutionary pressures the CNS has become immunologically specialized and now possesses the ability to HHS Public AccessAuthor manuscript Front Biosci. Author manuscript; available in PMC 2017 January 30.Published in final edited form as:Front Biosci. ; 13: 4529-4543. Author Manuscript Author ManuscriptAuthor Manuscript Author Manuscript modulate (or suppress) leukocyte behavior in a manner that fundamentally differs from that observed in most peripheral tissues. This evolutionary acquisition, which is advantageous from the standpoint of host survival, likely facilitates the entry and replication of viruses within the CNS. A multitude of viruses have the capacity to gain access to the CNS and upon doing so can establish a chronic infection, drive immunopathology, or alter the function of residents cells, making clearance of the invading pathogen essential. Therefore, a fundamental knowledge of viral-immune interactions in the CNS is essential if we ultimately intend to therapeutically modulate CNS immune responses in humans to achieve viral clearance in the absence of immunopathology. LCMV infection of mice provides an outstanding model system to explore such interactions and extend the lessons learned to virus infections of humans. GENERAL BACKGROUND ON LCMVLCMV is a natural pathogen of both human and murine populations (1). Human transmissio...

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Section: Lcmv Clone 13 Infection and Clearance From The Cnsmentioning

confidence: 98%

Section: Lcmv Clone 13 and Chronic Infectionmentioning

confidence: 99%

Section: Lcmv Clone 13 Infection and Clearance From The Cnsmentioning

confidence: 99%

Section: Lcmv Clone 13 Infection and Clearance From The Cnsmentioning

confidence: 99%

mentioning

confidence: 99%

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Lymphocytic choriomeningitis infection of the central nervous system

Kang

McGavern

2008

Front Biosci

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Interleukin 6 in Hyposmia

Henkin

Schmidt

Velicu

2013

JAMA Otolaryngol Head Neck Surg

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Compared with controls, IL-6 in patients was significantly elevated in plasma, saliva, and nasal mucus. Because IL-6 is a proinflammatory cytokine, these changes can relate to local or systemic inflammatory processes, which can be a cause or a result of pathological processes associated with hyposmia. These results support the concept that hyposmia has a biochemical basis and IL-6 may play a role in biochemical pathological processes underlying hyposmia and its treatment.

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Adaptive immune response to viral infections in the central nervous system

Libbey

Fujinami

2014

Handbook of Clinical Neurology

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Historically, the central nervous system (CNS) has been considered to be an immunologically privileged site within the body (Bailey et al., 2006; Galea et al. 2007; Engelhardt, 2008; Prendergast and Anderton, 2009). By definition, immunologically privileged sites, to include the brain, cornea, testis, and pregnant uterus, have a reduced/delayed ability to reject foreign tissue grafts compared to conventional sites within the body, such as skin (Streilein, 2003; Bailey et al., 2006; Carson et al., 2006; Mrass and Weninger, 2006; Kaplan and Niederkorn, 2007). In addition and conversely, tissue grafts prepared from immunologically privileged sites have increased survival, compared to tissue grafts prepared from conventional sites, when implanted at conventional sites (Streilein, 2003). The imune privilege of the CNS has been shown to be confined to the parenchyma, whereas the immune reactivity of the meninges and the ventricles, containing the choroid plexus, cerebrospinal fluid (CSF), and the circumventricular organs, is similar to conventionalsites (Carson et al., 2006; Engelhardt, 2006; Galea et al., 2007). This confinement of the imm une privilege to the parenchyma has also been demonstrated for experimental influenza virus infection in which confinement of the infection to the brain parenchyma did not result in efficient immune system priming whereas infection of the CSF elicited a virus-specific immune response comparable to that of intranasal infection (Stevenson et al. 1997). An important functional aspect of immune privilege is that damage due to the immune response and inflammation is limited within sensitive organs containing cell types that regenerate poorly, such as neurons within the brain (Mrass and Weninger, 2006; Galea et al.. 2007; Kaplan and Niederkorn, 2007).

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Clearance of an immunosuppressive virus from the CNS coincides with immune reanimation and diversification

Cited by 16 publications

References 63 publications

Lymphocytic choriomeningitis infection of the central nervous system

Lymphocytic choriomeningitis infection of the central nervous system

Interleukin 6 in Hyposmia

Adaptive immune response to viral infections in the central nervous system

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