RT Journal Article
T1 Pathological Characterization Of IFNAR(-/-) Mice Infected With Bluetongue Virus Serotype 4
A1 Marín López, Alejandro
A1 Bermúdez Pose, Roberto
A1 Calvo Pinilla, Eva
A1 Moreno, Sandra
A1 Brun, Alejandro
A1 Ortego, Javier
K1 Bluetongue virus
K1 IFNAR(-/-) mice
K1 Leukocyte
K1 Cytokine
K1 Pathology
AB Bluetongue virus (BTV) replicates in lymphoid tissues where infected mononuclear leukocytessecrete proinflammatory and vasoactive mediators that can contribute to bluetongue (BT)pathogenesis. Using the well-characterized IFNAR(-/-) mice animal model, we have now studiedthe histopathology and dynamics of leukocyte populations in different target tissues (spleen,thymus, and lung) during BTV-4 infection by histological and immunohistochemical techniques. Thespleen and thymus of BTV-4 infected mice showed severe lymphoid depletion on H&E stainedsections. This finding was confirmed by IHC, showing moderate decreased immunopositivityagainst CD3 in the thymus, and scarce immunoreactivity against CD3 and CD79 in the rest of thewhite pulp in the spleen, together with an increase in MAC387 immunostaining. BTV-4 infectionalso induced the expression of active caspase-3 in the spleen, where apoptotic debris wasobserved by H&E. A dramatic increase in iNOS immunoreactivity associated to necrotic areas ofthe white pulp was observed, being less noticeable in the thymus and the lung. The induction ofpro-inflammatory cytokines in tissues where BTV replicates was evaluated by measuring transcriptlevels by RT-qPCR. BTV-4 infection led to enhance transcription of IFN-γ, TNF, IL-6, IL-12-p40,and IL-1β mRNA in the thymus, spleen and lung, correlating with the level of virus replication inthese tissues. Disease progression and pathogenesis in IFNAR(-/-) mice closely mimics hallmarks ofbluetongue disease in ruminants. IFNAR(-/-) mice are a good choice to facilitate a faster advance inthe field of orbiviruses.
PB Ivyspring International Publisher
YR 2016
FD 2016
LK http://hdl.handle.net/10347/22372
UL http://hdl.handle.net/10347/22372
LA eng
NO Marín-López, A., Bermúdez, R., Calvo-Pinilla, E., Moreno, S., Brun, A., & Ortego, J. (2016). Pathological characterization of IFNAR (-/-) mice infected with bluetongue virus serotype 4. International journal of biological sciences, 12(12), 1448.
NO This work was supported by grants from the Comisión Interministerial de Ciencia y Tecnología (CICYT) (AGL2011-23506 and AGL-2014-57430-R)
DS Minerva
RD 4 may 2026