Innate Immune Response to Arenaviral Infection: A Focus on the Highly Pathogenic New World Hemorrhagic Arenaviruses

Koma, Takaaki; Huang, Cheng; Kolokoltsova, Olga A.; Brasier, Allan R.; Paessler, Slobodan

doi:10.1016/j.jmb.2013.09.028

Cited by 25 publications

(21 citation statements)

References 132 publications

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“…Robust in vitro memory CD4 + T-cell responses to LASV in antibody-seropositive surviving individuals suggested that efficient T-cell immunity develops during nonfatal infections (42). However, studies that measure the potency of T-cell responses or IFN-I levels in patients with lethal LF have not been reported (3)(4)(5)(6). We also noted that fatal vascular leakage in Cl13-infected NZB mice correlated with IFN-I-dependent platelet loss.…”

Section: Discussionmentioning

confidence: 59%

“…Studies in vitro with human cells and in vivo in nonhuman primates suggested reduced or delayed induction of type I IFNs (IFN-I), IFN-stimulated genes, and T-cell responses in fatal cases (1,(3)(4)(5)(6). However, these studies are limited by the small number of animals examined and the lack of direct comparisons between responses in patients with severe vs. mild infections.…”

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confidence: 99%

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Type I interferon is a therapeutic target for virus-induced lethal vascular damage

Baccalà¹,

Welch²,

Gonzalez-Quintial³

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Significance Lassa virus is, after dengue virus, the second most common cause of viral hemorrhagic fever. In susceptible individuals, Lassa virus infection is associated with vascular permeability, leading to tissue edema, organ failure, and death. Hemorrhagic fever viruses efficiently infect vascular endothelial cells, but are generally considered noncytopathic. Thus, the mechanism of virus-induced vascular injury remains unclear. Using the lymphocytic choriomeningitis virus variant clone 13, a prototype of Lassa virus, we show here that lethal vascular leakage in susceptible mice was completely prevented by type I IFN receptor blockade. Therefore, approaches that target type I IFNs or effector molecules induced by these cytokines may be considered for the treatment of Lassa fever and other severe hemorrhagic viral illnesses.

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Section: Discussionmentioning

confidence: 59%

mentioning

confidence: 99%

Type I interferon is a therapeutic target for virus-induced lethal vascular damage

Baccalà¹,

Welch²,

Gonzalez-Quintial³

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…World arenaviruses (20). We have previously found that the L protein and NP from the Cd#1 strain of JUNV efficiently support MACV replication in a minigenome system, suggesting the feasibility of introducing viral genes from the attenuated JUNV into MACV (18).…”

Section: Figmentioning

confidence: 99%

Machupo Virus Expressing GPC of the Candid#1 Vaccine Strain of Junin Virus Is Highly Attenuated and Immunogenic

Koma

Patterson

Huang

et al. 2016

J Virol

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Machupo virus (MACV) is the causative agent of Bolivian hemorrhagic fever. Our previous study demonstrated that a MACV strain with a single amino acid substitution (F438I) in the transmembrane domain of glycoprotein is attenuated but genetically unstable in mice. MACV is closely related to Junin virus (JUNV), the causative agent of Argentine hemorrhagic fever. Others and our group have identified the glycoprotein to be the major viral factor determining JUNV attenuation. In this study, we tested the compatibility of the glycoprotein of the Candid#1 live-attenuated vaccine strain of JUNV in MACV replication and its ability to attenuate MACV in vivo. Recombinant MACV with the Candid#1 glycoprotein (rMACV/Cd#1-GPC) exhibited growth properties similar to those of Candid#1 and was genetically stable in vitro. In a mouse model of lethal infection, rMACV/Cd#1-GPC was fully attenuated, more immunogenic than Candid#1, and fully protective against MACV infection. Therefore, the MACV strain expressing the glycoprotein of Candid#1 is safe, genetically stable, and highly protective against MACV infection in a mouse model. IMPORTANCECurrently, there are no FDA-approved vaccines and/or treatments for Bolivian hemorrhagic fever, which is a fatal human disease caused by MACV. The development of antiviral strategies to combat viral hemorrhagic fevers, including Bolivian hemorrhagic fever, is one of the top priorities of the Implementation Plan of the U.S. Department of Health and Human Services Public Health Emergency Medical Countermeasures Enterprise. Here, we demonstrate for the first time that MACV expressing glycoprotein of Candid#1 is a safe, genetically stable, highly immunogenic, and protective vaccine candidate against Bolivian hemorrhagic fever.

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“…Lassa hemorrhagic fever has many similar characteristics to Ebola virus disease, including the absence of interferon production and lymphoid depletion. On the molecular level, arenaviruses have been shown to suppress interferon production by targeting both upstream (i.e., RIG-I/MDA-5) and downstream signaling events (i.e., IKKε interactions, IRF-3 phosphorylation) (Koma et al, 2013). In this way each virus disrupts multiple access points in the pathways that lead to increased interferon production.…”

Section: Snipping the Alarm-wire: Preventing The Interferon Alarmmentioning

confidence: 99%

Camouflage and Misdirection: The Full-On Assault of Ebola Virus Disease

Misasi

Sullivan

2014

Cell

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Ebolaviruses cause a severe hemorrhagic fever syndrome that is rapidly fatal to humans and non-human primates. Ebola protein interactions with host cellular proteins disrupt Type I and Type II interferon responses, RNAi anti-viral responses, antigen presentation, T-cell mediated antibody responses, humoral antibodies and cell mediated immunity. This multifaceted approach to evasion and suppression of innate and adaptive immune responses in their target hosts leads to the severe immune dysregulation and “cytokine storm” that is characteristic of fatal ebolavirus infection. Here we highlight some of the processes by which Ebola interacts with its mammalian hosts to evade anti-viral defenses.

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Innate Immune Response to Arenaviral Infection: A Focus on the Highly Pathogenic New World Hemorrhagic Arenaviruses

Cited by 25 publications

References 132 publications

Type I interferon is a therapeutic target for virus-induced lethal vascular damage

Type I interferon is a therapeutic target for virus-induced lethal vascular damage

Machupo Virus Expressing GPC of the Candid#1 Vaccine Strain of Junin Virus Is Highly Attenuated and Immunogenic

Camouflage and Misdirection: The Full-On Assault of Ebola Virus Disease

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