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Establishment of HSV1 Latency in Immunodeficient Mice Facilitates Efficient Reactivation

English version České info

Although mouse models have been very useful in studies of HSV1 latency, the inability to efficiently reactivate latent HSV1 in vivo has impeded studies of reactivation. Reasoning that reactivation would be much more efficient in the absence of T cells, we exploited IVIG to promote survival of latently infected Rag mice lacking B and T cells. We established a threshold inoculum dose that was higher for B6- compared to 129-Rag mice, which determined whether HSV1 could be efficiently reactivated in vivo resulting in encephalitis. We showed directly that memory T cells are required to control spontaneous and induced reactivation in mice inoculated at high dose but are dispensable for maintaining latency in low dose inoculated mice. Incorporating different knockout strains into the Rag latency model by adoptive transfer of cells or crossbreeding will facilitate studying the role of various cellular genes involved in regulating neuronal gene expression and innate and adaptive immunity in the control of HSV1 reactivation. The potential of this powerful latency model to unravel the molecular and immune mechanisms regulating latency will be realized only after it is adopted and refined by researchers in the field.

Vyšlo v časopise: Establishment of HSV1 Latency in Immunodeficient Mice Facilitates Efficient Reactivation. PLoS Pathog 11(3): e32767. doi:10.1371/journal.ppat.1004730
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004730

Souhrn

Although mouse models have been very useful in studies of HSV1 latency, the inability to efficiently reactivate latent HSV1 in vivo has impeded studies of reactivation. Reasoning that reactivation would be much more efficient in the absence of T cells, we exploited IVIG to promote survival of latently infected Rag mice lacking B and T cells. We established a threshold inoculum dose that was higher for B6- compared to 129-Rag mice, which determined whether HSV1 could be efficiently reactivated in vivo resulting in encephalitis. We showed directly that memory T cells are required to control spontaneous and induced reactivation in mice inoculated at high dose but are dispensable for maintaining latency in low dose inoculated mice. Incorporating different knockout strains into the Rag latency model by adoptive transfer of cells or crossbreeding will facilitate studying the role of various cellular genes involved in regulating neuronal gene expression and innate and adaptive immunity in the control of HSV1 reactivation. The potential of this powerful latency model to unravel the molecular and immune mechanisms regulating latency will be realized only after it is adopted and refined by researchers in the field.

Zdroje

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PLOS Pathogens

2015 Číslo 3
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Aktuální možnosti diagnostiky a léčby litiáz
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Autori: MUDr. Tomáš Ürge, PhD.
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