A case of congenital lymphocytic choriomeningitis virus (LCMV) infection revealed by hydrops fetalis

2009 ◽  
Vol 29 (6) ◽  
pp. 626-627 ◽  
Author(s):  
J. F. Meritet ◽  
A. Krivine ◽  
F. Lewin ◽  
M. H. Poissonnier ◽  
R. Poizat ◽  
...  
Keyword(s):  
Lymphocytic Choriomeningitis ◽  
Lymphocytic Choriomeningitis Virus ◽  
Hydrops Fetalis ◽  
Lcmv Infection

Lymphocytic Choriomeningitis Virus

2018 ◽  
Author(s):  
Daniel J. Bonthius
Keyword(s):  
Infectious Virus ◽  
Clinical Presentation ◽  
Congenital Infection ◽  
Immunological Tolerance ◽  
Lymphocytic Choriomeningitis ◽  
Lymphocytic Choriomeningitis Virus ◽  
Long Term Prognosis ◽  
Lcmv Infection ◽  
Prevalent Pathogen

Lymphocytic choriomeningitis virus (LCMV), an arenavirus, is a prevalent pathogen and an important and underrecognized cause of neurologic birth defects. LCMV utilizes rodents as its principal reservoir. Rodents that acquire the virus transplacentally often remain asymptomatic because congenital infection provides immunological tolerance for the virus. Humans typically acquire LCMV by direct contact with fomites contaminated with infectious virus, from rodents, or by inhalation of aerosolized virus. Congenital LCMV infection occurs when a woman acquires the virus during pregnancy. The virus is passed to the fetus transplacentally, presumably during maternal viremia. Published reports of LCMV infection during pregnancy make it clear that LCMV can be a severe neuroteratogen. Prospective epidemiological or clinical studies of congenital LCMV infection are needed to gain more knowledge about the incidence and spectrum of LCMV-induced teratogenicity. The clinical presentation of congenital LCMV is reviewed, along with recommendations for diagnostic studies and information about long-term prognosis.

scholarly journals The CD8+ T-Cell Response to Lymphocytic Choriomeningitis Virus Involves the L Antigen: Uncovering New Tricks for an Old Virus

2007 ◽  
Vol 81 (10) ◽  
pp. 4928-4940 ◽  
Author(s):  
Maya F. Kotturi ◽  
Bjoern Peters ◽  
Fernando Buendia-Laysa ◽  
John Sidney ◽  
Carla Oseroff ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Response ◽  
Cellular Response ◽  
Lymphocytic Choriomeningitis ◽  
Lymphocytic Choriomeningitis Virus ◽  
T Cell Response ◽  
Ifn Γ ◽  
Lcmv Infection

ABSTRACT CD8+ T-cell responses control lymphocytic choriomeningitis virus (LCMV) infection in H-2b mice. Although antigen-specific responses against LCMV infection are well studied, we found that a significant fraction of the CD8+ CD44hi T-cell response to LCMV in H-2b mice was not accounted for by known epitopes. We screened peptides predicted to bind major histocompatibility complex class I and overlapping 15-mer peptides spanning the complete LCMV proteome for gamma interferon (IFN-γ) induction from CD8+ T cells derived from LCMV-infected H-2b mice. We identified 19 novel epitopes. Together with the 9 previously known, these epitopes account for the total CD8+ CD44hi response. Thus, bystander T-cell activation does not contribute appreciably to the CD8+ CD44hi pool. Strikingly, 15 of the 19 new epitopes were derived from the viral L polymerase, which, until now, was not recognized as a target of the cellular response induced by LCMV infection. The L epitopes induced significant levels of in vivo cytotoxicity and conferred protection against LCMV challenge. Interestingly, protection from viral challenge was best correlated with the cytolytic potential of CD8+ T cells, whereas IFN-γ production and peptide avidity appear to play a lesser role. Taken together, these findings illustrate that the LCMV-specific CD8+ T-cell response is more complex than previously appreciated.

scholarly journals Virus-induced Transient Bone Marrow Aplasia: Major Role of Interferon-α/β during Acute Infection with the Noncytopathic Lymphocytic Choriomeningitis Virus

1997 ◽  
Vol 185 (3) ◽  
pp. 517-530 ◽  
Author(s):  
Daniel Binder ◽  
Jörg Fehr ◽  
Hans Hengartner ◽  
Rolf M. Zinkernagel
Keyword(s):  
Bone Marrow ◽  
Nk Cells ◽  
Acute Infection ◽  
Lymphocytic Choriomeningitis ◽  
Lymphocytic Choriomeningitis Virus ◽  
Mouse Strains ◽  
Interferon Α ◽  
Wild Type ◽  
Ifn Γ ◽  
Lcmv Infection

The hematologic consequences of infection with the noncytopathic lymphocytic choriomeningitis virus (LCMV) were studied in wild-type mice with inherent variations in their interferon (IFN)-α/β responder ability and in mutant mice lacking α/β (IFN-α/β R0/0) or γ IFN (IFN-γ R0/0) receptors. During the first week of infection, wild type mice demonstrated a transient pancytopenia. Within a given genetic background, the extent of the blood cell abnormalities did not correlate with the virulence of the LCMV isolate but variations were detected between different mouse strains; they were found to depend on their IFN-α/β responder phenotype. Whereas IFN-γ R0/0 mice were comparable to wild-type mice, IFN-α/β R0/0 mice exhibited unchanged peripheral blood values during acute LCMV infection. In parallel, the bone marrow (BM) cellularity, the pluripotential and committed progenitor compartments were up to 30-fold reduced in wild type and IFN-γ R0/0, but remained unchanged in IFN-α/β R0/0 mice. Viral titers in BM 3 d after LCMV infection were similar in these mice, but antigen localization was different. Viral antigen was predominantly confined to stromal BM in normal mice and IFN-γ R0/0 knockouts, whereas, in IFN-α/β R0/0 mice, LCMV was detected in >90% of megakaryocytes and 10–15% of myeloid precursors, but not in erythroblasts. Although IFN-α/β efficiently prevented viral replication in potentially susceptible hematopoietic cells, even in overwhelming LCMV infection, unlimited virus multiplication in platelet and myeloid precursors in IFN-α/β R0/0 mice did not interfere with the number of circulating blood cells. Natural killer (NK) cell expansion and activity in the BM was comparable on day 3 after infection in mutant and control mice. Adaptive immune responses did not play a major role because comparable kinetics of LCMV-induced pancytopenia and transient depletion of the pluripotential and committed progenitor compartments were observed in CD80/0 and CD40/0 mice, in mice depleted of NK cells, in lpr mice, and in perforin-deficient (P0/0) mice lacking lytic NK cells. Thus, the reversible depression of hematopoiesis during early LCMV infection was not mediated by LCMV-WE–specific cytotoxic T lymphocyte, cytolysis, or secreted IFN-γ from virally induced NK cells but was a direct effect of IFN-α/β.

scholarly journals Thymic Tolerance to Only One Viral Protein Reduces Lymphocytic Choriomeningitis Virus-Induced Immunopathology and Increases Survival in Perforin-Deficient Mice

1999 ◽  
Vol 73 (7) ◽  
pp. 5918-5925 ◽  
Author(s):  
Matthias von Herrath ◽  
Bryan Coon ◽  
Dirk Homann ◽  
Tom Wolfe ◽  
Luca G. Guidotti
Keyword(s):  
Immune Response ◽  
Viral Protein ◽  
Selective Reduction ◽  
Lymphocytic Choriomeningitis ◽  
Lymphocytic Choriomeningitis Virus ◽  
Term Survival ◽  
Tnf Α ◽  
Ifn Γ ◽  
Deficient Mice ◽  
Lcmv Infection

ABSTRACT The outcome of viral infections is dependent on the amount of tissue destruction caused either by direct lysis of infected cells and/or by immunopathology resulting from the immune response to the virus. We investigated whether induction of tolerance to only one viral protein could reduce immunopathology caused by nonlytic lymphocytic choriomeningitis virus (LCMV) in perforin-deficient hosts. Earlier studies had shown that LCMV infection results in aplastic anemia and death in most of these mice and that this is associated with bone marrow infiltration by antiviral cytotoxic T lymphocytes (CTL) that secrete inflammatory cytokines. We report here that perforin-deficient mice exhibit severe immunopathology in multiple organs that is characterized by infiltration of anti-LCMV CTL that secrete large amounts of gamma interferon (IFN-γ) and tumor necrosis factor alpha (TNF-α). Importantly, this immunopathology is significantly reduced and long-term survival of LCMV infection is increased in perforin-deficient mice expressing LCMV nucleoprotein (NP) in the thymus (and therefore deleting most of their LCMV-NP CTL) compared to the situation in thymus nonexpressors. This is due to the selective reduction of NP-specific CTL responses and their inflammatory-cytokine (IFN-γ and TNF-α) secretion and to a lack of pathogenetically relevant compensatory responses to other viral proteins. Thus, “selective reduction” of the antiviral immune response to only one viral protein can significantly reduce inflammatory immunopathology and might be a therapeutic possibility for certain nonlytic infections.

scholarly journals PD-L1 Checkpoint Inhibition Narrows the Antigen-Specific T Cell Receptor Repertoire in Chronic Lymphocytic Choriomeningitis Virus Infection

2020 ◽  
Vol 94 (18) ◽  
Author(s):  
S. Klein ◽  
D. Ghersi ◽  
M. P. Manns ◽  
I. Prinz ◽  
M. Cornberg ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Cell Receptor ◽  
Lymphocytic Choriomeningitis ◽  
Lymphocytic Choriomeningitis Virus ◽  
Tcr Repertoire ◽  
Lcmv Infection

ABSTRACT Checkpoint inhibitors are effective in restoring exhausted CD8+ T cell responses in persistent viral infections or tumors. Several compounds are in clinical use for different malignancies, but trials in patients with chronic viral infections have also been conducted. In a mouse model of persistent lymphocytic choriomeningitis virus (LCMV) infection, it was shown that checkpoint inhibitor treatment increased T cell proliferation and functionality, but its influence on the antigen-specific T cell receptor (TCR) repertoire is unknown. NP396-specific CD8+ T cells dominate during acute LCMV infection and are predominantly exhausted during chronic infection. Next-generation sequencing of NP396-specific TCRs showed that exhaustion corresponds with a significantly reduced NP396-specific TCR repertoire diversity: Shannon indices of 4 in immunized mice to 2.6 in persistently infected mice. Anti-PD-L1 treatment during persistent LCMV infection restored NP396-specific T cell responses and reduced viral titers. Nevertheless, anti-PD-L1-treated mice showed an even more narrowed TCR repertoire, with reduced TCR diversity compared to that of persistently infected control mice (Shannon indices of 2.1 and 2.6, respectively). Interestingly, anti-PD-L1 treatment-induced narrowing of the TCR repertoire negatively correlates with functional and physical restoration of the antigen-specific T cell response. Further, we found that private, hyperexpanded TCR clonotypes dominated the T cell response after anti-PD-L1 treatment. Although being private, these top clonotypes from anti-PD-L1-treated mice revealed a more closely related CDR3 motif than those of top clonotypes from persistently infected control mice. In conclusion, although targeting the PD-1/PD-L1 pathway reinvigorates exhausted CD8+ T cells, it fails to restore T cell repertoire diversity. IMPORTANCE Checkpoint inhibitors are effective immunotherapeutics to restore cancer- and virus-induced exhausted CD8+ T cells, by enhancing the quality and survival of immune responses. Although checkpoint inhibitors are already used as therapy against various cancers, not much is known about their multifaceted impact on the exhausted CD8+ T cell receptor (TCR) repertoire. This report describes for the first time the evolvement of an exhausted antigen-specific CD8+ TCR repertoire under checkpoint inhibitor treatment. By using a well-established virus model, we were able to show major shifts toward oligoclonality of the CD8+ TCR repertoire response against a massively exhausted lymphocytic choriomeningitis virus (LCMV) epitope. While supporting viral control in the LCMV model, oligoclonality and more private of TCR repertoires may impact future pathogenic challenges and may promote viral escape. Our results may explain the ongoing problems of viral escapes, unpredictable autoimmunity, and heterogeneous responses appearing as adverse effects of checkpoint inhibitor treatments.

scholarly journals Noncytopathic Clearance of Lymphocytic Choriomeningitis Virus from the Hepatocyte

1999 ◽  
Vol 189 (10) ◽  
pp. 1555-1564 ◽  
Author(s):  
Luca G. Guidotti ◽  
Persephone Borrow ◽  
Amy Brown ◽  
Heike McClary ◽  
Rick Koch ◽  
...  
Keyword(s):  
Lymphocytic Choriomeningitis ◽  
Lymphocytic Choriomeningitis Virus ◽  
Tubular Epithelial Cells ◽  
Nonparenchymal Cells ◽  
Hbv Replication ◽  
B Virus ◽  
The Face ◽  
Lcmv Infection ◽  
Necrosis Factor

We have previously shown that interferon and tumor necrosis factor noncytopathically abolish hepatitis B virus (HBV) replication from the hepatocyte and kidney tubular epithelial cells in vivo. Here we show that a persistent lymphocytic choriomeningitis virus (LCMV) infection is cleared from the hepatocyte noncytopathically when the same cytokines are induced in the liver by antigen-nonspecific stimuli. These results indicate that, like HBV, LCMV is also susceptible to intracellular inactivation by cytokine-induced antiviral mechanisms that are operative in the hepatocyte. In contrast, LCMV is not cleared from intrahepatic nonparenchymal cells or splenocytes, indicating that, unlike the hepatocyte, these cells do not produce the factors required to inactivate LCMV. Antiviral mechanisms like these may have evolved to maintain the functional integrity of vital organs in the face of massive infection.

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