Endogenous Interferon in Argentine Hemorrhagic Fever

Abstract

The induction of endogenous interferon (IFN) was studied in 28 cases of Argentine hemorrhagic fever (AHF), a severe systemic disease caused by Junin virus. Serum samples were taken daily during the acute period, both before and after administration of immune plasma. This form of treatment has been found to reduce mortality when given early in the course of AHF. High titers of circulating IFN were present in the serum samples taken before treatment. IFN titers drastically dropped after transfusion of immune plasma. The antiviral activity was stable at pH 2 and was completely neutralized only by antibodies against IFN-alpha. Thus, we concluded that circulating endogenous IFN in patients with AHF can be considered as typical IFN-alpha. Fever, chills, and backache were associated with the higher levels of IFN. An inverse correlation between days of evolution of the disease and IFN activity was also observed.

Endothelial Cell Permeability and Adherens Junction Disruption Induced by Junín Virus Infection

“…Circulating IFNs have also been previously shown to play an important role in arenavirus-mediated diseases, with increased levels correlated to increased disease severity 5,[48][49][50] In this study, we were unable to detect IFN-α, -β, or -γ in human endothelial cells infected with JUNV. Although this result indicates that the cells themselves are not responding to infection with JUNV by expressing IFN, we cannot rule out the influence of immune cells and other intercellular signaling events that occur in vivo in response to JUNV infection; in vivo studies will be critical in addressing this issue.…”

“…2,3 Although the mechanisms of vascular instability during AHF are unknown, the paradigm is that mediators produced by virus-infected inflammatory cells contribute significantly. 5,6 However, endothelial cells are targeted to varying degrees by viruses causing VHFs, [7][8][9][10] and direct infection of these cells may also contribute to pathogenesis.…”

Viral targeting of hematopoietic progenitors and inhibition of DC maturation as a dual strategy for immune subversion

“…The role for IFN-α/β proposed in this manuscript may apply to other viruses such the Lassa or Junin arenaviruses, Dengue fever virus, and Ebola virus. Infection with these viruses results in high concentrations of IFN-α/β in the serum, and the magnitude and the duration of circulating IFN-α/β correlate directly with the severity and the evolution of the disease (61)(62)(63)(64)(65).…”

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

“…8,9 We have previously shown that increased levels of tumor necrosis factor-␣ (TNF-␣) in AHF patients were related to disease severity. 10 In contrast, circulating levels of interleukin-1␤ (IL-1␤) were not detected in these patients.…”