Attenuated and lethal variants of Pichindé virus induce differential patterns of NF-kappaB activation suggesting a potential target for novel therapeutics.
Lassa virus pathogenesis is believed to involve dysregulation of cytokines. We have previously shown nuclear factor-kappaB (NF-kappaB) inhibition using a BSL-2 model for Lassa fever. Here we further define the potential mechanism for NF-kappaB inhibition as involving increased levels of repressive p50/p50 homodimers, and suggest a novel therapeutic strategy that acts via modulation of host signaling.
Bowick
Gavin C
GC
Center for Biodefense and Emerging Infectious Diseases, University of Texas Medical Branch, Galveston, Texas 77555-0609, USA.
Fennewald
Susan M
SM
Zhang
Lihong
L
Yang
Xianbin
X
Aronson
Judith F
JF
Shope
Robert E
RE
Luxon
Bruce A
BA
Gorenstein
David G
DG
Herzog
Norbert K
NK
D000818:Animals; D001117:Arenaviridae Infections / Q000188:drug therapy*; D000081247:CSK Tyrosine-Protein Kinase; D003673:Defective Viruses / Q000472:pathogenicity* / Q000502:physiology; D016503:Drug Delivery Systems; D066298:In Vitro Techniques; D051379:Mice; D009000:Monocytes / Q000821:virology*; D016328:NF-kappa B / Q000378:metabolism*; D052002:NF-kappa B p50 Subunit / Q000378:metabolism; D010766:Phosphorylation; D018052:Pichinde virus / Q000472:pathogenicity* / Q000502:physiology; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D015398:Signal Transduction; D051996:Transcription Factor RelA / Q000378:metabolism; D014158:Transcription, Genetic; D014774:Virulence; D019061:src-Family Kinases
D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; C498144:Rela protein, mouse; D051996:Transcription Factor RelA; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases