Imported Lassa Fever in Germany: Molecular Characterization of a New Lassa Virus Strain

Günther, Stephan; Emmerich, Petra; Laue, Thomas M.; Kühle, Olaf; Asper, Marcel; Jung, Annegret; Grewing, Thomas; Meulen, Jan ter; Schmitz, Herbert

doi:10.3201/eid0605.000504

Cited by 176 publications

(144 citation statements)

References 38 publications

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“…Although our model probably does not re-create all the aspects of virus-DC interactions in a patient, the generation of T-cell responses using iDC is a relevant approach to studying the immunogenicity of viral antigens (9,30,38,62,71,76). The comparison of MV, as a surrogate of "nonpathogenic LV," and the pathogenic AV strain of LV (4,34) is justified by their close evolutionary relationship, their common natural host (12), and the cross-protection induced in NHP (26). However, this study does not entirely explain the different issues observed after human infection with LV.…”

Section: Discussioncontrasting

confidence: 47%

“…The AV strain of LV was preferred to the Josiah strain because the two strains are closely related, and the former was recently isolated from a fatally infected patient. Therefore, this strain is very close to the LV currently circulating in zones of endemicity, and it has been subjected to a limited number of passages since its isolation from the patient's serum (34). In addition, both strains are considered highly pathogenic LV strains (4).…”

Section: Methodsmentioning

confidence: 99%

“…LV AV strain from the serum of a patient (34) and MV AN 23166 strain isolated from a Mastomys sp. (75) were subjected to four passages on Vero E6 cells at 37°C under a 5% CO 2 atmosphere in Dulbecco's modified Eagle medium supplemented with 50 IU/ml penicillin-streptomycin, 1% nonessential amino acids (all from Invitrogen, Cergy-Pontoise, France), and 2% AB ϩ human serum (Etablissement Français du Sang, Lyon, France).…”

Section: Methodsmentioning

confidence: 99%

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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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Section: Discussioncontrasting

confidence: 47%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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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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“…Virus LV (AV strain (21)) was cultured in the Vero E6 cell line at 37°C. Viruses from the serum of a patient were subjected to four passages on Vero E6 cells.…”

Section: Methodsmentioning

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

191

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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“…Marmosets have recently been reported as an alternative nonhuman primate model for LV infection (10), and lymphocytic choriomeningitis virus (LCMV) has been used as a surrogate for LV in the macaque model (35,39). Here, we report the infection of cynomolgus monkeys with a primary strain of LV, the AV strain (23), and describe the virological and immunological parameters associated with fatal and nonfatal outcomes.…”

mentioning

confidence: 99%

Early and Strong Immune Responses Are Associated with Control of Viral Replication and Recovery in Lassa Virus-Infected Cynomolgus Monkeys

Baize

Marianneau

Loth

et al. 2009

J Virol

168

213

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Lassa virus causes a hemorrhagic fever endemic in West Africa. The pathogenesis and the immune responses associated with the disease are poorly understood, and no vaccine is available. We followed virological, pathological, and immunological markers associated with fatal and nonfatal Lassa virus infection of cynomolgus monkeys. The clinical picture was characterized by fever, weight loss, depression, and acute respiratory syndrome. Transient thrombocytopenia and lymphopenia, lymphadenopathy, splenomegaly, infiltration of mononuclear cells, and alterations of the liver, lungs, and endothelia were observed. Survivors exhibited fewer lesions and a lower viral load than nonsurvivors. Although all animals developed strong humoral responses, antibodies appeared more rapidly in survivors and were directed against GP 1 , GP 2 , and NP. Type I interferons were detected early after infection in survivors but only during the terminal stages in fatalities. The mRNAs for CXCL10 (IP-10) and CXCL11 (I-TAC) were abundant in peripheral blood mononuclear cells and lymph nodes from infected animals, but plasma interleukin-6 was detected only in fatalities. In survivors, high activated-monocyte counts were followed by a rise in the total number of circulating monocytes. Activated T lymphocytes circulated in survivors, whereas T-cell activation was low and delayed in fatalities. In vitro stimulation with inactivated Lassa virus induced activation of T lymphocytes from all infected monkeys, but only lymphocytes from survivors proliferated. Thus, early and strong immune responses and control of viral replication were associated with recovery, whereas fatal infection was characterized by major alterations of the blood formula and, in organs, weak immune responses and uncontrolled viral replication.

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Imported Lassa Fever in Germany: Molecular Characterization of a New Lassa Virus Strain

Cited by 176 publications

References 38 publications

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

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

Early and Strong Immune Responses Are Associated with Control of Viral Replication and Recovery in Lassa Virus-Infected Cynomolgus Monkeys

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