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HTLV-1 infection and neuropathogenesis in the context of Rag1−/−γc−/− (RAG1-hu) and BLT mice
Journal article   Open access   Peer reviewed

HTLV-1 infection and neuropathogenesis in the context of Rag1−/−γc−/− (RAG1-hu) and BLT mice

Kiran Kumar Madagula, Rashida Ginwala, Breanna Caruso, Zafar K Khan, Glen M Chew, Ajinkya Pattekar, Michael J. Corley, Ronak Loonawat, Steven Jacobson, Sreesha Sreedhar, …
The Journal of immunology (1950), v 198(1_Supplement), pp 78-78.29
01 May 2017
DOI: https://doi.org/10.4049/jimmunol.198.Supp.78.29
url
https://europepmc.org/articles/pmc5529230View
Accepted (AM)Open Access (License Unspecified),  Open

Abstract

Abstract To date, the lack of a suitable small animal model has hindered our quest to understand the immuno- and neuropathogenesis of HTLV-1, the causative agent of chronic disabling neuroinflammatory disease HAM/TSP. Host immune response that plays a critical role in the outcome of HTLV-1 infection could be better tested in the context of humanized (hu) mice. Thus, we infected neonatal and adult Balb/c-Rag1−/−γc−/− (Rag1) as well as Bone marrow-Liver-Thymic (BLT) mice with HTLV-1. Proviral load (PVL) was determined in the peripheral blood, spleen, and other organs by droplet digital PCR. Within blood, PVL and viral protein Tax was detected as early as 2 wks post-infection (wpi). Tax showed peak expression at 14 wpi in Rag1 mice with continued expression until 16 weeks. Both PVL and Tax expression was considerably higher in the adult Rag1 mice as compared to the neonates with the latter showing less than 20% PVL in the peripheral blood, brain, and liver. Moreover, signs of lymphocytic infiltration with concomitant Tax expression and resulting myelin disruption were observed in the spinal cord and brain of infected mice. Thus far, several members of the CD28:B7 family of co-signaling molecules have been associated with T-cell dysfunctions in HTLV-infected patients. We found increased expression of PD-1, TIGIT and TIM-3 on CD8+ T cells in the CNS of infected hu-mice. This represents the first attempt to establish HTLV-1 neuropathogenesis in the context of Rag-1 and BLT hu-mice suggesting the possibility of developing a small animal model of HAM/TSP for testing groundbreaking therapies.

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