Characterization of Human CD4<sup>+</sup>T-Cell Clones Recognizing Conserved and Variable Epitopes of the Lassa Virus Nucleoprotein

Meulen, Jan ter; Badusche, Marlis; Kuhnt, Kristiane; Doetze, Andrea; Satoguina, Judith; Marti, Thomas; Loeliger, Cornelius; Koulémou, Kékoura; Koivogui, Lamine; Schmitz, Herbert; Fleischer, Bernhard; Hoerauf, Achim

doi:10.1128/jvi.74.5.2186-2192.2000

Cited by 100 publications

(108 citation statements)

References 33 publications

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“…It has previously been shown that during acute LCMV infection, functional CD4 ϩ T cell responses led to effective CTL responses and viral clearance (8,39,58). Interestingly, in the case of the related Lassa fever virus, seropositive individuals from endemic areas have strong memory CD4 ϩ T cells responses against the virus (59,60). In the case of HIV infection, strong CD4 ϩ T cell responses are detected in individuals who are treated with antivirals early in the course of infection, suggesting that CD4 ϩ T cell responses can be maintained if viral replication is contained (5,61,62).…”

Section: Discussionmentioning

confidence: 99%

Chronic Lymphocytic Choriomeningitis Virus Infection Actively Down-Regulates CD4+ T Cell Responses Directed against a Broad Range of Epitopes

Mothé

Stewart

Oseroff

et al. 2007

The Journal of Immunology

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Activation of CD4+ T cells helps establish and sustain CD8+ T cell responses and is required for the effective clearance of acute infection. CD4-deficient mice are unable to control persistent infection and CD4+ T cells are usually defective in chronic and persistent infections. We investigated the question of how persistent infection impacted pre-existing lymphocytic choriomeningitis virus (LCMV)-specific CD4+ T cell responses. We identified class II-restricted epitopes from the entire set of open reading frames from LCMV Armstrong in BALB/c mice (H-2d) acutely infected with LCMV Armstrong. Of nine epitopes identified, six were restricted by I-Ad, one by I-Ed and two were dually restricted by both I-Ad and I-Ed molecules. Additional experiments revealed that CD4+ T cell responses specific for these epitopes were not generated following infection with the immunosuppressive clone 13 strain of LCMV. Most importantly, in peptide-immunized mice, established CD4+ T cell responses to these LCMV CD4 epitopes as well as nonviral, OVA-specific responses were actively suppressed following infection with LCMV clone 13 and were undetectable within 12 days after infection, suggesting an active inhibition of established helper responses. To address this dysfunction, we performed transfer experiments using both the Smarta and OT-II systems. OT-II cells were not detected after clone 13 infection, indicating physical deletion, while Smarta cells proliferated but were unable to produce IFN-γ, suggesting impairment of the production of this cytokine. Thus, multiple mechanisms may be involved in the impairment of helper responses in the setting of early persistent infection.

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Section: Discussionmentioning

confidence: 99%

Chronic Lymphocytic Choriomeningitis Virus Infection Actively Down-Regulates CD4+ T Cell Responses Directed against a Broad Range of Epitopes

Mothé

Stewart

Oseroff

et al. 2007

The Journal of Immunology

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“…LV infection in humans seems to be controlled primarily by T-cell responses. Memory CD4 ϩ T cells directed against the viral nucleoprotein and glycoproteins circulate in LV-seropositive subjects (66,67), whereas neutralizing antibodies are detected at low titers only after recovery, and the production of specific immunoglobulin G (IgG) is not correlated with recovery (39). Furthermore, T-cell responses, but not antibody production, are correlated with protection of NHP against a lethal LV challenge after immunization and with the survival of naïve animals with LF (7,26,33).…”

mentioning

confidence: 99%

Human Dendritic Cells Infected with the Nonpathogenic Mopeia Virus Induce Stronger T-Cell Responses than Those Infected with Lassa Virus

Pannetier¹,

Reynard²,

Russier³

et al. 2011

J Virol

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The events leading to death in severe cases of Lassa fever (LF) are unknown. Fatality seems to be linked to high viremia and immunosuppression, and cellular immunity, rather than neutralizing antibodies, appears to be essential for survival. We previously compared Lassa virus (LV) with its genetically close but nonpathogenic homolog Mopeia virus (MV), which was used to model nonfatal LF. We showed that strong and early activation of antigen-presenting cells (

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“…Humoral responses cannot control viral replication and the appearance of specific IgG in patients and infected monkeys is not correlated with recovery (11,12). The induction of cellular responses specific for viral glycoproteins protects nonhuman primates from a lethal challenge (12), and memory CD4 ϩ T cell responses against NP have been demonstrated in seropositive endemic subjects (13). In contrast, severe LV infections seem to be associated with high levels of viremia and immunosuppression.…”

mentioning

confidence: 99%

Lassa Virus Infection of Human Dendritic Cells and Macrophages Is Productive but Fails to Activate Cells

Baize

Kaplon

Faure

et al. 2004

The Journal of Immunology

192

208

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Lassa fever is a hemorrhagic fever caused by Lassa virus (LV), an old-world Arenavirus. Little is known about the immune responses that occur during the disease, but protection seems to be linked to the induction of cellular responses specific for viral glycoproteins. Conversely, severe Lassa fever may be associated with immunosuppression. We studied the infection of human dendritic cells (DC) and macrophages (MP) by LV. Both these cell types are susceptible to LV infection. Viral nucleoprotein was detected in DC and MP, and high and moderate viral titers were obtained with culture supernatants of DC and MP, respectively. LV did not induce apoptosis in DC and MP. These cells were not activated by LV infection. No change was observed in the expression of surface molecules involved in activation, costimulation, adhesion, and Ag presentation following LV infection, or in the functional properties of DC. Inflammatory cytokine production was not detected at the mRNA or protein level after LV infection of DC and MP. Thus, MP, and particularly DC, are crucial targets for LV and are probably involved in the early replication of LV from the initial site of infection. The lack of activation and maturation of cells following infection may be associated with the immunosuppression observed in severe LV infection.

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Characterization of Human CD4⁺T-Cell Clones Recognizing Conserved and Variable Epitopes of the Lassa Virus Nucleoprotein

Cited by 100 publications

References 33 publications

Chronic Lymphocytic Choriomeningitis Virus Infection Actively Down-Regulates CD4+ T Cell Responses Directed against a Broad Range of Epitopes

Chronic Lymphocytic Choriomeningitis Virus Infection Actively Down-Regulates CD4+ T Cell Responses Directed against a Broad Range of Epitopes

Human Dendritic Cells Infected with the Nonpathogenic Mopeia Virus Induce Stronger T-Cell Responses than Those Infected with Lassa Virus

Lassa Virus Infection of Human Dendritic Cells and Macrophages Is Productive but Fails to Activate Cells

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Characterization of Human CD4+T-Cell Clones Recognizing Conserved and Variable Epitopes of the Lassa Virus Nucleoprotein

Cited by 100 publications

References 33 publications

Chronic Lymphocytic Choriomeningitis Virus Infection Actively Down-Regulates CD4+ T Cell Responses Directed against a Broad Range of Epitopes

Chronic Lymphocytic Choriomeningitis Virus Infection Actively Down-Regulates CD4+ T Cell Responses Directed against a Broad Range of Epitopes

Human Dendritic Cells Infected with the Nonpathogenic Mopeia Virus Induce Stronger T-Cell Responses than Those Infected with Lassa Virus

Lassa Virus Infection of Human Dendritic Cells and Macrophages Is Productive but Fails to Activate Cells

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Characterization of Human CD4⁺T-Cell Clones Recognizing Conserved and Variable Epitopes of the Lassa Virus Nucleoprotein