Proinflammatory cytokines and elastase-alpha-1-antitrypsin in Argentine hemorrhagic fever.

Marta, Rosana Fernanda; Montero, Verónica S.; Hack, C. E.; Sturk, A.; Maiztegui, Julio I.; Molinas, Felisa C.

doi:10.4269/ajtmh.1999.60.85

Cited by 66 publications

(41 citation statements)

References 35 publications

(23 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been reported that during JUNV infection, macrophages and dendritic cells are the initial sites of viral replication (9,27) and are involved in spreading the virus to other tissues (36). It has been suggested that this initial infection of macrophages might be responsible for the source of the elevated cytokine levels seen during Junín virus infection (30,37,39). Indeed, we showed here that Candid 1 induced production of IFN-␤ and TNF-␣ and that this induction was strongest between 2 and 4 hpi.…”

Section: Discussionsupporting

confidence: 57%

Junín Virus Infects Mouse Cells and Induces Innate Immune Responses

Cuevas

Lavanya

Wang

et al. 2011

J Virol

View full text Add to dashboard Cite

Junín virus is the causative agent for Argentine hemorrhagic fever, and its natural host is the New World rodent Calomys musculinus. The virus is transmitted to humans by aerosolization, and it is believed that many of the clinical symptoms are caused by cytokines produced by sentinel cells of the immune system. Here we used the Junín virus vaccine strain Candid 1 to determine whether mouse cells could be used to study virus entry and antiviral innate immune responses. We show that Candid 1 can infect and propagate in different mousederived cell lines through a low-pH-dependent, transferrin receptor 1-independent mechanism, suggesting that there is a second entry receptor. In addition, Candid 1 induced expression of the antiviral cytokines tumor necrosis factor alpha and beta interferon in macrophages, and this induction was independent of viral replication. Using Candid 1, as well as virus-like particles bearing the viral glycoprotein, to infect different primary cells and established macrophage cell lines with deletions in the Toll-like receptor (TLR) pathway, we show that TLR2 is a cellular sensor of both the Parodi and Candid 1 viral glycoproteins. Because Junín virus is highly lethal in humans, the use of an experimentally tractable model system, such as the mouse, could provide a better understanding of the antiviral innate cellular responses to Junín virus and the role of these responses in pathogenesis.

show abstract

Section: Discussionsupporting

confidence: 57%

Junín Virus Infects Mouse Cells and Induces Innate Immune Responses

Cuevas

Lavanya

Wang

et al. 2011

J Virol

View full text Add to dashboard Cite

show abstract

“…These results are in agreement with our observation that TCRV-NP is not as efficient as other arenavirus NPs in blocking IFN-I (53) and NF-B responses (this work). Intriguingly, although increased production of IFN-␣, IFN-␤, TNF-␣, IL-6, IL-10, or IL-12 was not observed in JUNVinfected human monocytes or macrophages, several pro-and anti-inflammatory cytokines have been shown to occur at elevated levels in patients with fatal or severe JUNV infection (25,44,50), a situation similar to that observed in human cases of LASV infection (47). However, studies of LASV infection of cynomolgus monkeys have shown a correlation between an early and strong innate immune response and control of virus multiplication and recovery from LASV-induced disease (34).…”

Section: Discussionmentioning

confidence: 99%

Arenavirus Nucleoproteins Prevent Activation of Nuclear Factor Kappa B

Rodrigo

Ortiz-Riaño

Pythoud

et al. 2012

J Virol

View full text Add to dashboard Cite

cArenaviruses include several causative agents of hemorrhagic fever (HF) disease in humans that are associated with high morbidity and significant mortality. Morbidity and lethality associated with HF arenaviruses are believed to involve the dysregulation of the host innate immune and inflammatory responses that leads to impaired development of protective and efficient immunity. The molecular mechanisms underlying this dysregulation are not completely understood, but it is suggested that viral infection leads to disruption of early host defenses and contributes to arenavirus pathogenesis in humans. We demonstrate in the accompanying paper that the prototype member in the family, lymphocytic choriomeningitis virus (LCMV), disables the host innate defense by interfering with type I interferon (IFN-I)

show abstract

“…On the other hand, for several of the viral haemorrhagic fevers, it has been suggested that overproduction of proinflammatory cytokines such as IL-1b and TNF-a late in the disease course may contribute to vascular endothelial dysfunction and consequent shock (Geisbert & Jahrling, 2004;Marta et al, 1999). The small number of reported human studies do not support this idea for arenavirus haemorrhagic fevers consistently (Mahanty et al, 2001;Schmitz et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Cytokine patterns in a comparative model of arenavirus haemorrhagic fever in guinea pigs

Scott

Aronson

2008

Journal of General Virology

View full text Add to dashboard Cite

Arenaviruses such as Lassa virus cause a spectrum of disease in humans ranging from mild febrile illness to lethal haemorrhagic fever. The contributions of innate immunity to protection or pathogenicity are unknown. We compared patterns of expression of cytokines of innate immunity in mild versus severe arenavirus disease using an established guinea pig model based on the macrophage-tropic arenavirus Pichinde virus (PICV). Cytokine transcripts were measured by using real-time RT-PCR in target organs and blood during mild infection (caused by PICV, P2 variant) and lethal haemorrhagic fever (caused by PICV, P18 variant). In the initial peritoneal target cells, virulent P18 infection was associated with significantly increased gamma interferon (IFN-γ) and monocyte chemoattractant protein-1 (MCP-1, CCL2) mRNA levels relative to P2 infection. Peritoneal cells from P18-infected animals had decreased tumour necrosis factor alpha (TNF-α), interleukin (IL)-8 (CXCL-8) and IL-12p40 transcripts relative to mock-infected animals. Late in infection, P18-infected peripheral blood leukocytes (PBL) had decreased TNF-α, IFN-γ, and regulated upon activation, normal T cell expressed and secreted (RANTES, CCL-5) cytokine transcripts relative to P2-infected PBL. We conclude that, in severe arenavirus disease, patterns of cytokine expression in the initially infected cells favour recruitment of additional target monocytes, while inhibiting some of their pro-inflammatory responses. Suppression rather than overexpression of pro-inflammatory cytokines accompanied the terminal shock in this model of arenavirus haemorrhagic fever.

show abstract

Proinflammatory cytokines and elastase-alpha-1-antitrypsin in Argentine hemorrhagic fever.

Cited by 66 publications

References 35 publications

Junín Virus Infects Mouse Cells and Induces Innate Immune Responses

Junín Virus Infects Mouse Cells and Induces Innate Immune Responses

Arenavirus Nucleoproteins Prevent Activation of Nuclear Factor Kappa B

Cytokine patterns in a comparative model of arenavirus haemorrhagic fever in guinea pigs

Contact Info

Product

Resources

About