Arenavirus Nucleoproteins Prevent Activation of Nuclear Factor Kappa B

Abstract

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)

Exonuclease Domain of the Lassa Virus Nucleoprotein Is Critical To Avoid RIG-I Signaling and To Inhibit the Innate Immune Response

“…The role of ExoN activity in the inhibition of IRF-3 translocation and, consequently, in the inhibition of the IFN-␤-and NF-B-mediated responses has been demonstrated in vitro with recombinant NP (10,11,23). We provide here the first demonstration of the crucial role of the ExoN function during infection.…”

The Exonuclease Domain of Lassa Virus Nucleoprotein Is Involved in Antigen-Presenting-Cell-Mediated NK Cell Responses

“…A recent study showed that LASV and other arenavirus NPs inhibit the translocation and transcriptional activity of nuclear factor-B (NF-B) (34). Moreover, the authors reported that recombinant lymphocytic choriomeningitis virus containing D382A and G385A substitutions (corresponding to 389 and 392 in LASV sequence, respectively) failed to inhibit NF-B activation.…”

The Human Cytomegalovirus UL26 Protein Antagonizes NF-κB Activation

“…TNF-␣ or Sendai virus (SeV) induction of the NF-B-dependent reporter plasmid pNF-B-FF (RelAspecific vector) was done as described previously (29). SeV induction of the IRF3-dependent reporter plasmid (p55C1B-FF) was described previously (30).…”